12 955 PART 12 STRUCTURAL AND MECHANICAL ABNORMALITIES CHAPTER 66 Neuromuscular and Chest Wall Disorders Oscar Henry Mayer, Karen Webster Gripp, Julian Lewis Allen, and Mary Ellen Beck Wohl The chest wall serves as a protective cage for the heart, lungs, and great vessels of the thorax and as the respiratory pump that drives respiration. This chapter discusses normal developmental chest wall structure and function, as well as the causes and treatment of chest wall and neuromuscular disorders. GROWTH AND DEVELOPMENT OF THE CHEST WALL Structural Changes with Growth Major structural changes occur in the chest wall with growth, and these changes have important functional implications for respiratory pump efficiency and function. In infancy, the ori- entation of the ribs is horizontal, but with growth they slowly rotate downward in a caudal declination until the normal adult pattern of downward-sloping ribs occurs at about 10 years of age 1 (Fig. 66-1). Chest wall muscle mass increases progressively with development. Ossification of the chest wall begins in utero and continues to approximately the 25th year. Progressive calcification of the costal cartilages can con- tinue into old age. Functional Consequences of Developmental Structural Changes of the Chest Wall MECHANICAL PROPERTIES Specific chest wall compliance decreases progressively with growth. In the infant, compliance of the chest wall is three to six times that of the lung. 2-5 Chest wall compliance is greater in preterm infants 3 than in full-term infants and decreases further during the first 2 years of life. 6 In school- age children, chest wall compliance is approximately twice that of the lung 7 ; in the mature adult, it is equal to that of the lung, and in the elderly, it may be half that of the lung 8 (Fig. 66-2). These changes in chest wall compliance are in part due to increasing ossification of the chest wall with development and increasing calcification with aging. Increasing muscle mass also contributes to the decrease in chest wall compliance with age. 9-11 Although it is advantageous to have a highly compliant chest wall during the birthing process, functional disadvan- tages occur in infancy. With diaphragm contraction and downward diaphragm motion pleural pressure becomes nega- tive. In a fully mature ribcage, the external intercostal muscles also contract as the ribs rotate superiorly and laterally, increas- ing the cross-sectional area of the thorax and expanding the lungs effectively. However, in a young or premature infant with higher chest wall compliance, due to the absence of full rib ossification and full intercostal muscle activity, the nega- tive pleural pressure during inspiration may cause inward motion of the ribcage. 12 In addition, with the ribs rotated out in a more horizontal orientation, the diaphragm may be more flat with a smaller area of apposition to the chest wall, causing lower rib cage inward motion with diaphragm con- traction, because the plane of contraction will be more horizontal. 12 TEACHING POINTS ● There is a decrease in chest wall compliance from infancy through adulthood due to both ossification of the ribs and an increase in chest wall muscle mass. ● The component of tidal volume from rib cage excursion relative to the abdominal excursion increases from infancy through adulthood. ● The inspiratory action of the diaphragm includes decreas- ing intrapleural pressure, expanding the lower rib cage, and increasing intra-abdominal pressure. ● The fatigue resistance of the diaphragm can change based on the mechanical load of the respiratory system. ● Although respiratory muscle training can be useful in conditions of deconditioning, it is not recommended in patients with progressive neuromuscular disease. ● While surgery for pectus excavatum can correct the visual defect, it often does not produce a significant improve- ment in lung volumes or forced expiratory flows. ● Early diagnosis and treatment of scoliosis are very impor- tant in minimizing the impact on lung function. ● Congenital diaphragmatic hernia is often associated with pulmonary hypoplasia of both the affected and the un- affected sides. ● Progressive neuromuscular disease can cause both chronic respiratory failure and poor airway clearance, which can put further load on the respiratory system.
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P A R T 12STRUCTURAL AND MECHANICAL ABNORMALITIES
CHAPTER66 Neuromuscular and Chest Wall DisordersOscar Henry Mayer, Karen Webster Gripp, Julian Lewis Allen, and Mary Ellen Beck Wohl
The chest wall serves as a protective cage for the heart, lungs, and great vessels of the thorax and as the respiratory pump that drives respiration. This chapter discusses normal developmental chest wall structure and function, as well as the causes and treatment of chest wall and neuromuscular disorders.
GROWTH AND DEVELOPMENT OF THE CHEST WALL
Structural Changes with Growth
Major structural changes occur in the chest wall with growth, and these changes have important functional implications for respiratory pump effi ciency and function. In infancy, the ori-entation of the ribs is horizontal, but with growth they slowly
rotate downward in a caudal declination until the normal adult pattern of downward-sloping ribs occurs at about 10 years of age 1 (Fig. 66-1). Chest wall muscle mass increases progressively with development. Ossifi cation of the chest wall begins in utero and continues to approximately the 25th year. Progressive calcifi cation of the costal cartilages can con-tinue into old age.
Functional Consequences of Developmental Structural Changes of the Chest Wall
MECHANICAL PROPERTIESSpecifi c chest wall compliance decreases progressively with growth. In the infant, compliance of the chest wall is three to six times that of the lung. 2-5 Chest wall compliance is greater in preterm infants 3 than in full-term infants and decreases further during the fi rst 2 years of life. 6 In school-age children, chest wall compliance is approximately twice that of the lung 7 ; in the mature adult, it is equal to that of the lung, and in the elderly, it may be half that of the lung 8 (Fig. 66-2).
These changes in chest wall compliance are in part due to increasing ossifi cation of the chest wall with development and increasing calcifi cation with aging. Increasing muscle mass also contributes to the decrease in chest wall compliance with age. 9-11
Although it is advantageous to have a highly compliant chest wall during the birthing process, functional disadvan-tages occur in infancy. With diaphragm contraction and downward diaphragm motion pleural pressure becomes nega-tive. In a fully mature ribcage, the external intercostal muscles also contract as the ribs rotate superiorly and laterally, increas-ing the cross-sectional area of the thorax and expanding the lungs effectively. However, in a young or premature infant with higher chest wall compliance, due to the absence of full rib ossifi cation and full intercostal muscle activity, the nega-tive pleural pressure during inspiration may cause inward motion of the ribcage. 12 In addition, with the ribs rotated out in a more horizontal orientation, the diaphragm may be more fl at with a smaller area of apposition to the chest wall, causing lower rib cage inward motion with diaphragm con-traction, because the plane of contraction will be more horizontal. 12
TEACHING POINTS
● There is a decrease in chest wall compliance from infancy through adulthood due to both ossifi cation of the ribs and an increase in chest wall muscle mass.
● The component of tidal volume from rib cage excursion relative to the abdominal excursion increases from infancy through adulthood.
● The inspiratory action of the diaphragm includes decreas-ing intrapleural pressure, expanding the lower rib cage, and increasing intra-abdominal pressure.
● The fatigue resistance of the diaphragm can change based on the mechanical load of the respiratory system.
● Although respiratory muscle training can be useful in conditions of deconditioning, it is not recommended in patients with progressive neuromuscular disease.
● While surgery for pectus excavatum can correct the visual defect, it often does not produce a signifi cant improve-ment in lung volumes or forced expiratory fl ows.
● Early diagnosis and treatment of scoliosis are very impor-tant in minimizing the impact on lung function.
● Congenital diaphragmatic hernia is often associated with pulmonary hypoplasia of both the affected and the un -affected sides.
● Progressive neuromuscular disease can cause both chronic respiratory failure and poor airway clearance, which can put further load on the respiratory system.
C DFigure 66-1 Changes in ribcage morphometry with growth. A and B, Posteroanterior (PA) and lateral chest radiographs of a 4-month-old infant. C and D, PA and lateral chest radiographs of a 14-year-old boy. In the infant, the slope of the ribs is nearly horizontal, whereas in the 14-year-old, there is a downward declination of the ribs. Progressive ossifi cation of the sternal ossifi cation centers can be seen in the lateral radiograph.
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more poorly compliant lungs predispose a child to an even lower Vr, and expiratory braking is clearly manifested as “grunting.” Normal active maintenance of EEV diminishes with age and during the second year of life disappears, 21 likely as a result of progressive stiffening of the chest wall allowing a higher passively determined EEV. 6,22,23
DEVELOPMENT OF THE RESPIRATORY MUSCLES
Structural and Functional Changes
The diaphragm has three major inspiratory actions. 24,25 First, the diaphragm decreases intrapleural pressure by acting as a piston, thereby creating a gradient of pressure that favors air fl ow from the airway opening to the alveoli. Second, the diaphragm increases intra-abdominal pressure. Because a sub-stantial portion of intra-abdominal contents actually resides within the ribcage (Fig. 66-5), this increased abdominal pres-sure causes the lower ribcage to expand. Third, the dia-phragm increases lower ribcage dimensions by acting through its area of apposition (see Fig. 66-5) to the inner ribcage wall to elevate the lower ribs, the “fulcrum” effect. This elevation
Infant 5-18 yr 30 yr 60 yr
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Figure 66-2 Changes in the ratio of chest wall to lung compliance with aging. Data for infants represent a range from several studies. In infants and children, the chest wall is more compliant than the lungs; in adults the chest wall compliance is close to that of the lungs, and in the elderly it is less than that of the lungs. CW, wall compliance; CL, lung compliance.
Few studies have been done on developmental changes in chest wall resistance. The chest wall accounts for approxi-mately 30% to 35% of total respiratory system resistance in adults 13 and 20% to 25% in infants. 6,14
MAINTENANCE OF FUNCTIONAL RESIDUAL CAPACITYThe passive relaxation volume of the respiratory system (Vr) is determined by the balance of two opposing forces: the outward recoil of the chest wall and the inward recoil of the lung 15 (Fig. 66-3). The highly compliant chest wall of an infant provides less outward recoil and produces a low Vr. If Vr falls below the volume at which airway closure occurs, atelectasis can occur. Furthermore, during inspiration, additional energy needs to be expended to open these closed airways before inspiratory airfl ow occurs. This mode of breathing places an unnecessary metabolic burden on a patient.
Instead, full-term infants adopt a strategy of active main-tenance of end-expiratory lung volume (EEV), consisting of an active prolongation of expiration. This phenomenon can be observed by comparing the active tidal breathing fl ow-volume curve with the passive fl ow-volume curve elicited by relaxing the respiratory muscles with a brief end-inspiratory occlusion, which activates the Hering-Breuer refl ex 16 (Fig. 66-4). The active and passive time constants are represented by the slopes of the expiratory limb of these curves. The EEV can be maintained above Vr by increasing the expiratory time constant, τ, of the respiratory system relative to the time actually available for expiration. 17 This slower exhalation interrupts expiratory fl ow at a lung volume above the relaxed level (see Fig. 66-4) and will minimize airway closure. Preterm infants also maintain EEV above Vr, but their ability to do so is markedly sleep-state dependent, being less effective in active than in quiet sleep.
The neonate accomplishes active prolongation of expira-tion via two mechanisms: post–inspiratory activity of the inspiratory muscles, such as the diaphragm, 18 and expiratory “braking” by the upper airway muscles, 19,20 or vocal cord adduction. In infants with hyaline membrane disease, the
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Figure 66-3 Respiratory system PV curves in the newborn and adult human. The x-axis represents pressure and the y-axis represents volume. The slope of each curve at a given lung volume represents the compliance at that volume. The solid curve in each diagram is the PV curve of the respiratory system. At a given lung volume, it represents the sum of the pressures resulting from the chest wall PV curve (left dashed line) and the lung PV curve (right dashed line). Passive end-expiratory lung volume is represented by the point at which the solid curve crosses the volume axis. It is lower in the newborn than in the adult because of the high compliance of the newborn chest wall curve. (Redrawn from Agostoni E, Mead J: Statics of the respiratory system. In Fenn WO, Rahn H [eds]: Handbook of Physiology, Respiration, Section 3, Volume 1. Washington, DC, 1964, American Physiological Society, p 401.)
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Figure 66-4 Elevation of EEV by active prolongation of the respiratory system time constant, t. A tidal fl ow volume curve is shown on the oscilloscope tracing. The slope of the expiratory limb of this curve ([volume, mL/kg]/[fl ow, mL/{sec • kg}]) has the units of seconds and represents the active expiratory time constant, texp. The slope of the dotted line represents the passive time constant of the respiratory system (trs) following an end-inspiratory occlusion that activates the Hering-Breuer refl ex and relaxes the respiratory muscles. The lines intersect at the passive relaxation volume (Vr). The volume difference between Vr and the active fl ow-volume curve EEV represents the difference between functional residual capacity (FRC) and Vr and refl ects active maintenance of FRC. (Reprinted with permission from Mortola JP, Saetta M: Pediatr Pulmonol 3:123-130, 1987.)
Figure 66-5 Zone of apposition. Whereas there is a substantial portion of the abdomen that is within the ribcage, there is apposition of the diaphragm and the inner chest wall (see circled area). (Reprinted with permission from DeTroyer A, Loring SH: Clin Chest Med 9:175-193, 1988.)
of the lower ribs also expands the lower thoracic cross-sectional area by causing the downward-sloping ribs to assume a more horizontal position, the “bucket handle” effect (Fig. 66-6).
In addition, there are a number of other factors that impact on the mechanical effi ciency of diaphragm contrac-tion. Less of the ribcage’s contents are intra-abdominal and the area of apposition is smaller in the infant than that in the older child and adult. Furthermore, diaphragmatic mass is less in the infant. 11 Theoretically, these differences should
Rib 6
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Bucket-handle motion
Figure 66-6 Bucket handle effect. [Reprinted with permission from DeTroyer A, Loring SH: Action of the respiratory muscles. In Macklem PT, Mead J [eds]: Handbook of Physiology. The Respiratory System. Mechanics of Breathing, Section 3, Volume III, Part 2. Bethesda, MD, 1986, American Physiological Society, p 453.)
impair the infant diaphragm’s inspiratory action. On the other hand, by the law of Laplace, the smaller radius of cur-vature of the infant’s diaphragm relative to the adult should improve its pressure-generating ability at a given level of tension.
Tidal expiration is primarily driven by the passive elastic recoil of the respiratory system. Neonates, like adults, can recruit abdominal muscles to promote active expiration, 26,27 although this is highly sleep-state dependent and is much less effective in rapid eye movement (REM) than in non-REM sleep.
Developmental Cell Biology of the Respiratory Muscles and Implications for Fatigue Resistance
It has been suggested that the mechanical disadvantage imposed by a highly compliant chest wall will predispose the premature and newborn infant to respiratory muscle fatigue and respiratory pump failure. 28-30 However, there are molec-ular and contractile properties that impart a certain fatigue resistance in newborn and young infants.
Developmental Changes in Respiratory Muscle Fiber Type Determined by Histochemistry
The relative proportion of type I (slow twitch, fatigue resis-tant) and type II fi bers (fast twitch, fatigable) in respiratory muscles changes with development. The percent composition of type I fi bers in the diaphragm of human premature infants, newborns, and older children (older than 2 years) is 10%, 25%, and 55%, respectively, 28 and there is a similar develop-mental pattern with the intercostal muscles. 28 Therefore, it would be reasonable to conclude that premature and newborn infants would be more susceptible to respiratory muscle fatigue than older children. Le Souëf and associates 29 found a paucity of type I fi bers in the newborn rabbit diaphragm and an impaired ability to maintain occlusion pressure during sustained activation of the diaphragm by phrenic nerve stimu-lation. However, Maxwell and associates 31 found that the respiratory muscles of premature baboons were highly oxida-tive and fatigue resistant. Therefore there are other factors to consider than muscle fi ber types.
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Sieck 32 and Watchko 33 and associates have demonstrated that although specifi c force (peak tetanic force output nor-malized for muscle cross-sectional area) of diaphragmatic fi bers increases with postnatal age, fatigue resistance decreases with age. They also found that fatigue resistance is related not only to oxidative capacity of the muscle (indexed by suc-cinic dehydrogenase [SDH] activity), but also to myosin heavy chain (MHC) phenotype. 34 The neonatal MHC phe-notype seems to impart a greater degree of fatigue resistance than do the adult isoforms. Therefore, fatigue resistance of respiratory muscle during development may relate to a balance between the energetic demands of the muscle con-tractile proteins (refl ected by MHC isoform composition) and its oxidative capacity (refl ected by SDH activity). 34 However, high oxidative capacity, while promoting fatigue resistance, may lead to oxidative damage if not balanced by increased antioxidant enzymes, such as superoxide dismutase (SOD). 35
Recently, it has been determined that the fatigue resis-tance of respiratory muscles is plastic, and can change in the face of increasing resistive loads. Patients with chronic obstructive pulmonary disease (COPD) have diaphragms with an increased proportion of fatigue resistant type I fi bers and an increased percentage of slow MHC isoform I com-pared with control subjects’ diaphragms, which have fewer type I fi bers and an increased percentage of fast MHC iso-forms IIa and IIb. 36 Furthermore, fatigue-resistant develop-mental (embryonic and neonatal) MHCs have been reported in the diaphragms of patients with COPD, but their numbers are actually reduced compared with controls. 37 This may reduce the effectiveness of type I fi bers in combating fatigue.
METHODS FOR ASSESSING CHEST WALL FUNCTION
Chest Wall Motion
The quantitation of chest wall motion gives information about both chest wall and underlying lung function. The most widely used method to assess chest wall motion is respiratory inductive plethysmography; although video motion capture, strain gauges, and magnetometers have been used as well. 38
Thoracoabdominal motion is more asynchronous with decreased or increased chest wall compliance and with increased airways resistance 39-41 (Fig. 66-7). In patients with increased chest wall compliance, the contraction of the dia-phragm during inspiration produces a drop in pleural pressure and increase in abdominal pressure. The highly compliant ribcage may have inward motion at the same time the highly compliant abdomen has outward motion. 23 With increased airways resistance or decreased chest wall compliance, the diaphragm will have to contract more to generate the nega-tive pleural pressure needed for adequate air fl ow and ventila-tion. The diaphragm motion will cause outward abdominal motion and the delay to outward chest wall excursion is dependent on the work needed to overcome chest wall com-pliance and/or airways resistance.
In the different situation of increased chest wall com-pliance as seen in premature infants and children with neu-romuscular weakness such as spinal muscular atrophy,
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Figure 66-7 Relationship between thoracoabdominal asynchrony, quantitated by RC-AB phase angle, and lung mechanics. A, Phase angle versus resistance. B, Phase angle versus compliance. FT, full-term control; infants. BPD, bronchopulmonary dysplasia. (Redrawn from Allen JL, et al: Pediatr Pulmonol 11:37-43, 1991.)
progressive increase in negative pleural pressure will cause inward as opposed to outward ribcage motion. Even at rest, to maintain adequate ventilation there will be increased outward abdominal motion.
Timing relationships between ribcage (RC) and abdomen (AB) excursion can be quantitated by measuring the period delay between maximal RC and AB excursions on a scalar tracing. This can also be measured by plotting RC versus AB motion in a Lissajous, or Konno-Mead fi gure 42 and calculating the phase angle based on the shape of the resultant fi gure (Fig. 66-8). The phase angle is an index of thoracoabdominal motion (TAM). This phase angle can range from 0 degrees (synchronous RC-AB motion) to 180 degrees (paradoxical RC-AB motion).
Premature infants normally display asynchronous or para-doxical breathing during quiet sleep (mean phase angle 58 degrees, range 0 to 157 degrees). 43 In different studies, the normal phase angle is 8 to 13 degrees in awake full-term infants, 39 15 degrees in preschool-age children, 44 and 8 degrees in adolescents. 45 However, there are no longitudinal data through childhood to evaluate the variation of phase angle with age. There is signifi cant variability with position, with phase angle being higher when supine than when sitting or standing and lowest in the sitting position. 44
The magnitude of the contribution of the ribcage (RC) and abdominal (AB) compartments to tidal volume can also
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be quantitated. Newborn infants breathe predominantly with their abdominal compartments, as opposed to adults, who are primarily ribcage breathers. The ribcage’s contribution to tidal breathing during quiet sleep in the newborn is 35% of tidal volume (range 20% to 50%), increasing gradually over the fi rst year to the normal adult value of 65%. 46
Clinical Assessment of Respiratory Pump Function and Fatigue
PHYSICAL EXAMINATION OF THE CHEST WALLParadoxical motion of the ribcage and abdomen is easy to identify, although lesser degrees of thoracoabdominal asyn-chrony may be more diffi cult to discern. However, determin-ing the amount of thoracoabdominal asynchrony relative to the phase of respiration can be very useful. Although chest wall paradox can be observed visually, the phase of respiration may be ascertained by a fi ngertip held at the mouth to feel airfl ow, a hand on the chest to feel chest wall excursion, or by chest auscultation. Inspiratory inward RC motion with outward AB motion occurs in patients with increased ribcage compliance, such as premature infants, and in some normal infants during REM sleep. It also occurs in patients with neuromuscular disease with intercostal muscle weakness but intact diaphragmatic function, such as spinal muscular atrophy (SMA) and quadriplegia. Inspiratory outward AB motion sig-nifi cantly ahead of outward RC motion is present in infants and children with increased airway resistance or decreased ribcage compliance. Inspiratory outward RC and inward AB motion is seen in patients with diaphragmatic dysfunction. It can also be seen in adults with severe airfl ow obstruction and impending diaphragm fatigue.
Roussos and associates 47 described a pattern of “respira-tory alternans” during inspiratory resistive loaded breathing, in which breathing alternates between using the diaphragm and intercostal muscles, possibly postponing the onset of or attenuating respiratory muscle fatigue. One would expect this to be refl ected in an alternating pattern of RC and AB motion, with outward motion primarily in the RC on one breath followed by primarily AB motion in another breath, with each compartment’s displacement alternating in magni-
tude. Asynchronous RC/AB motion may also merely refl ect the magnitude of the load itself, rather than respiratory muscle fatigue per se. 39,48,49
Although the driving pressure for exhalation is the inward elastic recoil of the respiratory system, the abdominal muscles (particularly the rectus abdominis) may contract during active exhalation. This occurs in patients with severe obstruc-tive lung disease, in whom passive recoil of the respiratory system may provide insuffi cient pressure to overcome expira-tory airfl ow obstruction. Active expiration occurs normally during exercise. Alternately, it can be seen in some patients with inspiratory muscle weakness who may “actively” exhale below their functional residual capacity (FRC); the succeed-ing inspiration is then augmented by the outward elastic recoil of the chest wall from below FRC to FRC.
ASSESSMENT OF RESPIRATORY MUSCLE STRENGTHNormal adults can develop maximal inspiratory and expira-tory pressures against an occluded airway in excess of −100 and 200 cm H2O, respectively. Occlusion pressures can be measured during crying in infants as young as one month of age. Changes in maximal inspiratory and expiratory pressures with age are shown in Table 66-1.
The gender difference in Pemax and Pimax is thought by some to be due to the difference in muscle mass with gender. 50 Pimax has been measured and reported from both residual volume (RV) and FRC, so it is important to make note of the volume at measurement for appropriate comparisons. 50,51
Alternately, sniff inspiratory pressure (sniff Pi) through a single nostril, with the contralateral nostril occluded and mouth closed, was shown to be a useful surrogate in patients with neuromuscular disease, some of whom may not be able to perform an adequate Pimax via mouthpiece. 52 While the sniff inspiratory pressure in a cohort of children and adults with neuromuscular disease was similar to Pimax, 52 there was a signifi cant difference in a separate study of healthy chil-dren. 53 However, there was a signifi cant correlation between sniff inspiratory pressure and Pimax in both studies. 52,53
Maximal inspiratory force is an index of inspiratory muscle strength that is used by some clinicians in weaning a patient
Figure 66-8 Lissajous fi gures of ribcage (RC) and abdominal wall (AB) motion. Phase angle, φ, is an index of thoracoabdominal asynchrony. Increasing thoracoabdominal asynchrony is seen as increasing width of the fi gure up to a phase angle of 90 degrees and then by a change from a positive to a negative slope between 90 and 180 degrees. For phase angles 0 < φ < 90 degrees, sin φ = m/sec; for 90 < φ < 180 degrees, φ = 180 − µ, where sin µ = m/sec (see text). (Redrawn with permission from Allen JL, et al: Am Rev Respir Dis 141:337-342, 1990.)
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from mechanical ventilation, although its utility is not uni-versally accepted. 54 Transdiaphragmatic pressure (Pdi) is a measure of the pressure output of the diaphragm and is an index of diaphragmatic strength; however, it is more diffi cult to measure, requiring the placement of both gastric and esophageal pressure monitors.
Inspiratory muscle force is sometimes measured following either electrical or magnetic stimulation of the phrenic nerves. 55 While these techniques eliminate the variability inherent in volitional efforts, they are not widely clinically applied in pediatrics. 56,57
ASSESSMENT OF RESPIRATORY MUSCLE FATIGUEMeasurement of the tension time index and frequency pattern assessment of diaphragmatic electromyogram (EMG) activity have been proposed as indicators of impending respi-ratory muscle failure.
Respiratory muscle fatigue can be defi ned as an inability of the respiratory muscles to maintain the force required to sustain minute ventilation in the presence of a mechanical load. The development of fatigue is closely linked to the force and duration of muscle contraction. The tension time index of the diaphragm (TTId) is a dimensionless product of the ratio of developed Pdi to maximal transdiaphragmatic pres-sure (Pdimax) and the ratio of the inspiratory time (Ti) to the respiratory cycle time (Ttot), also known as the “duty cycle.”
Eq 66.1 TTId = Pdi/Pdimax • Ti/Ttot
The TTId has been used in adults to predict the development of fatigue. When the TTId exceeds 0.2, it is highly likely that fatigue will occur. The measurement of the TTId requires the ability to assess Pdi and Pdimax, which can be technically dif-fi cult, because these measurements require both esophageal and gastric pressure transducers to measure the pressure generated across the diaphragm. A few studies have been done in infants and children to determine whether the same values of the tension time index are applicable. 58
In a test analogous to the TTId, termed the TTmus, the tension time index of all the inspiratory muscles and not just the diaphragm is measured without the use of catheters. An
inspiratory occlusion pressure measured at the mouth 100 milliseconds after the onset of inspiration is extrapolated to end inspiration. The mean inspiratory pressure (Pi) is calcu-lated, and divided by the maximal inspiratory pressure measured at the mouth at FRC (MIP). The TTmus is then calculated as
TTmus = Pi (mean)/MIP • Ti/Ttot Eq 66.2
This test has the advantage of being noninvasive and has been used to assess susceptibility to respiratory muscle fatigue in children with cystic fi brosis and neuromuscular disease 59-61 (Fig. 66-9).
Spectral frequency analysis of the surface diaphragmatic EMG during fatiguing loads has been shown to indicate dia-phragmatic muscle fatigue in adults. 62 Similarly, in infants diaphragmatic fatigue produces a decrease in the high-frequency power and an increase in the low-frequency power of the EMG. 63 During weaning from mechanical ventilation, the EMG power spectrum remained normal in infants who were able to be weaned successfully, whereas in infants who failed extubation and in whom mechanical ventilation had to be reinstituted, a decrease in the high/low power spectrum ratio occurred before CO2 retention and clinical deteriora-tion. Because shifts in the diaphragmatic EMG power spec-trum may occur in the absence of fatigue, 64 this technique has limited clinical use. Accurate placement of electrodes is critical to adequate recording of power spectra and at present this technique is seldom used for clinical purposes.
A joint statement of the American Thoracic Society and the European Respiratory Society 57 addresses many of the technical aspects of the measurement of both respiratory muscle strength and fatigue in children.
TREATMENT OF RESPIRATORY PUMP FATIGUE
General Principles
Respiratory pump fatigue can result from three mechanisms: intrinsic pulmonary disease (e.g., COPD or interstitial lung
Table 66-1Measurements of Respiratory Muscle Strength in Childhood
Age GenderPoint of Measurement
Sniff Pi(cm H2O ± SD)
Pimax
(cm H2O ± SD)Pemax
(cm H2O ± SD) Citation
3-36 mo M & F RV; TLC (crying) −118 ± 21 125 ± 35 (1)
4-11 yr M FRC −83 ± 26 −73 ± 28 (2)
F FRC −79 ± 29 −62 ± 28 (3)
8-10 yr M RV; TLC −79 ± 31 95 ± 34 (3)
F RV; TLC −68 ± 24 82 ± 29 (3)
11-14 yr M RV; TLC −111 ± 31 147 ± 34 (3)
F RV; TLC −89 ± 27 115 ± 33 (3)
15-17 yr M RV; TLC −129 ± 24 180 ± 43 (3)
F RV; TLC −97 ± 24 133 ± 35 (3)
From (1) Shardonofsky F, Perez-Chada D, Carmuega E, Milic-Emili J: Airway pressures during crying in healthy infants. Pediatr Pulmonol 6:14-18, 1989; (2) Rafferty GF, Leech S, Knight
L, et al: Sniff nasal inspiratory pressure in children. Pediatr Pulmonol 29:468-475, 2000; and (3) Domenech-Clar R, López-Andrev JA, Compte-Torrero L, et al: Maximal static respiratory
pressures in children and adolescents. Pediatr Pulmonol 35:126-132, 2003.
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Although the technology for noninvasive ventilation was developed for adults, there are a few interfaces that are made specifi cally for children, but a larger number of adult masks that come in sizes small enough to use in children. Even though there are no noninvasive ventilators approved for use in children, they can be used effectively in children. Alter-nately, ventilation can also be done invasively via a tracheos-tomy tube using invasive ventilators designed for outpatient use. Ventilation can be used on an intermittent basis, on demand by mouthpiece or by nasal mask at night or during naps, for the majority of the day, or continuously with pro-gression of disease or during periods of illness.
There are many modes of chronic ventilation used for muscle rest. Support can be full, giving complete respiratory muscle rest, or partial, with the respiratory muscles still doing some work. What is used is based both on patient need and desire.
Assisted ventilation can improve gas exchange, and the results can persist after discontinuation of ventilation. 65 This improved gas exchange can be due to improved respiratory muscle strength or may be due to a “resetting” of the respira-tory control center to a lower PCO2 during the period of assisted ventilation. 66,67 In addition, although brief periods of intermittent positive-pressure breathing do not alter lung mechanics, 68 the increase in tidal volume during nocturnal assisted ventilation can reexpand areas of atelectasis that had developed during nonassisted breathing.
While nocturnal ventilation can reduce respiratory muscle fatigue by effecting respiratory muscle rest, continual mechanical ventilation may actually reduce respiratory muscle endurance, probably by a “deconditioning” effect. Patients in intensive care units requiring mechanical ventila-tion for greater than 48 hours have reduced respiratory muscle endurance immediately after weaning, and the degree of reduction is worsened by longer duration of mechanical ventilation. 59
Respiratory Muscle Training
Training can increase the strength and endurance of skeletal muscle. Strength and endurance training differ, as do the cellular changes that occur during each type of training. Strength training involves few repetitions of a high-intensity stimulus, and the major cellular response is muscle fi ber hypertrophy. Endurance training involves frequent repeti-tions of a low-intensity stimulus, and the major cellular response is increased oxidative capacity, with increases in oxidative enzymes, 69 capillary density, 70 with a decrease in cross-sectional area. 71
In normal adults respiratory muscle strength and endur-ance can be increased by specifi c training. 72 Respiratory muscle strength training has been performed using repeti-tions of maximal forced respiratory maneuvers and resistive loaded breathing with high inspiratory resistive loads. Endur-ance training has been accomplished with nonspecifi c (i.e., total body exercise) conditioning and specifi c conditioning. Specifi c endurance programs include voluntary isocapneic hyperventilation, resistive loaded breathing, and inspiratory threshold loading. In one recent study, athletes who under-went specifi c inspiratory muscle training increased strength by 25% and endurance by 27%. 73
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Figure 66-9 A, TTmus in normal children (yellow) and children with cystic fi brosis (purple). (Reprinted with permission from Hayot M, et al: Pediatr Pulmonol 23:336-343, 1997.) B, TTmus in children with neuromuscular disease (square) and healthy children (circles). (Reprinted with permission from Mulreany LT, et al: J Appl Physiol 95:931-937, 2003.)
disease) that increases the resistive or elastic work of breath-ing, muscle failure (e.g., neuromuscular disease), or chest wall deformity (e.g., scoliosis or fl ail chest) that decreases pump effi ciency. All these mechanisms may be thought of in terms of Pdi/Pdimax, the fi rst term of the TTI. Whereas an increased work of breathing increases the quantity (Pdi/Pdimax) by increasing Pdi, respiratory muscle weakness and ineffi ciency increases the quantity (Pdi/Pdimax) by decreasing Pdimax. Respiratory pump fatigue can be treated by respira-tory muscle rest, respiratory muscle training, and the use of pharmacologic agents, all of which can increase Pdimax. Obvi-ously, reducing the work the diaphragm has to do (Pdi) by treating the underlying disorder is crucial in treating respira-tory fatigue as well.
Respiratory Muscle Rest
Assisted ventilation is the most common form of respiratory muscle rest therapy. It can be done noninvasively via nasal, oral, and oronasal interfaces and also using negative pressure ventilation in subjects without upper airway obstruction.
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Respiratory muscle training has been shown to increase respiratory muscle strength and endurance in patients with quadriplegia. 74-76 A major unresolved question is when respi-ratory muscles should be exercised and when they should be rested. A general principle is that weak muscles should be exercised and fatigued muscles should be rested. 77,78 In Duchenne muscular dystrophy, the results of muscle training are varied from positive results that persist for a period of time after training ceases to no signifi cant change. 79-84 It remains controversial, however, whether respiratory muscle training in patients with neuromuscular disease may lead to further muscle damage due to a decreased capacity to recover from the stress on the muscles from training. 56 Some have suggested that this risk can be minimized with endurance, limited load, high frequency training. 84 The American Thoracic Society currently does not recommend respiratory muscle training in patients with Duchenne muscular dystrophy. 56 There is some thought that other cytoskeletal components might be able to be upregulated to make the muscles of patients with Duchenne muscular dystrophy more tolerant of exertion and training. 85
Pharmacotherapy of Respiratory Muscle Fatigue
Theophylline is the most studied pharmacologic agent for respiratory muscle fatigue. In vitro, theophylline produces a dose-dependent increase in peak twitch tension of the dia-phragm 86 and can attenuate fatigue if used prophylactically. 87 In animal models, theophylline increases maximal trans-diaphragmatic pressure 88 and improves diaphragmatic force generation after fatigue has developed. 89,90 In experimental spinal cord transection theophylline pretreatment as an ade-nosine type 1 receptor antagonist preserved diaphragm func-tion and improved recovery, and the effect persisted after the theophylline was stopped. 91 This effect was increased with pretreatment with adenosine type 2 agonist. 91 Other work has demonstrated that sepsis-induced diaphragm fatigue may be mediated through NO-mediated lipid peroxidation of diaphragm myofi brils and that pharmacologic inhibition of inducible NO in this model prevented much of the contrac-tile dysfunction. 92-94 Other work has shown that pretreat-ment with lidocaine can have a similar antioxidant effect. 95,96 However, in humans, there is only published experience with theophylline.
In healthy patients, theophylline has a potent effect on diaphragmatic contractility 97 and in patients with COPD, theophylline increases diaphragmatic strength and postpones the onset of diaphragmatic fatigue induced by resistive loaded breathing. Aminophylline increases diaphragmatic excursions in preterm infants, 98 but whether this is a central or periph-eral effect is unclear.
STRUCTURAL ABNORMALITIES OF THE CHEST WALL INCLUDING THE DIAPHRAGM
Thoracic Dystrophies
A number of disorders of development of the chest wall exist, many of which are uncommon and result in early death from associated pulmonary hypoplasia, respiratory mechanical ineffi ciency, and respiratory pump failure. 99 If the defect
occurs early enough in gestation to affect mesenchymal development it will negatively impact both airway and vas-cular development. If the thoracic defect occurs late in gesta-tion or post-partum, then it may cause vascular and airway derecruitment that may be reversible after correction of the defect.
The etiologies of a number of these disorders have recently been elucidated as the genetic control of bone and cartilage growth and development becomes more clearly understood 100 and can replace classifi cations based on radiographic and mor-phologic characteristics 101,102 (Table 66-2).
Genetic Mechanisms
Congenital anomalies of the chest wall can occur due to embryologic anomalies or due to underlying gene mutations. The VATER (vertebral, anal, tracheoesophageal fi stula, radial and renal anomalies) association is an example of an embryo-logic anomaly without a known genetic cause and no signifi -cant recurrence risk. 103 In contrast, disorders caused by gene mutations may have a recurrence risk and may be present in family members. It is therefore important to understand the inheritance pattern and to discuss this with family members at risk.
Osteogenesis imperfecta (see Table 66-2) is an example of autosomal dominant conditions that act via a dominant negative mechanism. Osteogenesis imperfecta results from a mutation in one of the genes encoding a procollagen chain. 104-107 Mature collagen molecules consist of three pro-collagen chains forming a triple helical structure. Incorpora-tion of a single structurally abnormal component disrupts this complex structure and leads to the abnormal connective tissue properties and brittle bones. Another example of a disease acting by dominant negative action is Marfan syn-drome, in which an abnormal fi brillin-1 gene causes abnormal fi brillin to be incorporated into extracellular microfi brils.
A second mechanism by which autosomal dominant muta-tions result in abnormal phenotypes is gain of function of the gene product. Achondroplasia is caused by a recurrent spe-cifi c heterozygous point mutation in the fi broblast growth factor receptor 3 gene (FGFR3). This membrane-bound receptor has an intracellular tyrosine kinase domain that is activated upon ligand binding and ultimately regulates cell proliferation. The function of the normal receptor is negative regulation of endochondral growth, as demonstrated by skel-etal overgrowth seen in mice lacking both functional copies of the gene. 108 The pathogenesis of the mutation involves constitutive activation of FGFR3, inhibiting proliferation of growth plate chondrocytes and causing short limb dwarfi sm.
A third pathogenic mechanism that causes autosomal dominant skeletal disorders is haploinsuffi ciency for the func-tional gene product. This mechanism most often affects protein products acting as transcription factors that control the expression of other genes. A 50% decrease of the func-tional protein is disease-causing in dosage-sensitive pathways, as seen in campomelic dysplasia and cleidocranial dysostosis (see Table 66-2).
A fourth pathogenic mechanism causing autosomal domi-nant disorders is that in which loss of function mutations in one gene copy are not functionally restored by a second,
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normal copy of the gene. While similar to the haploinsuffi -ciency mechanism, these mutations do not usually affect transcription factors. For example, mutation in the trans-forming growth factor β receptors 1 or 2 (TGFBR1 or TGFBR2) can cause Loeys-Dietz syndrome if only one copy of the gene is abnormal (see Table 66-2).
In contrast, autosomal recessive disorders are due to loss or function mutations in both alleles of the respective gene, causing loss of function protein products with enzymatic or transport function. Examples of these disorders include dias-trophic dwarfi sm, achondrogenesis type 1B, and Jarcho-Levin syndrome. For example, achondrogenesis type 1B causes a clinical syndrome of extreme short stature, poor ossifi cation of the skull and vertebral bodies, severe micromelia of the limbs, extremely short ribs, and stellate long bones. 103 The mutation resides in the diastrophic dysplasia sulfate trans-porter (DTDST) gene, 109 leading to decreased or absent sulfate transport 110 and abnormalities in cartilage proteogly-can sulfation.
Clinical Syndromes
Achondroplasia, an autosomal dominant skeletal dysplasia, is one of the most common forms of short-limbed dwarfi sm. It results from a mutation in the transmembrane domain of FGFR3. 100 Phenotypically, it is associated with developmen-tal abnormalities of the ribs, thorax, long bones, and cranium. The ribs are short and fl ared, and the anteroposterior diame-ter of the thorax is narrowed, which can compress the inter-vening structures such as the trachea. 111 This compression may be related to the posterior ribs bowing around the trans-verse processes of the spine, thus “pushing” the vertebral bodies anteriorly.
The respiratory complications of achondroplasia include disordered sleep and obstructive apnea in about three quar-ters of subjects, 112 due to brainstem compression causing disorders in the control of breathing and midface hypoplasia. In addition to obstructive apnea, in part related to the midface hypoplasia, brainstem compression may lead to disorders in the control of breathing. 112-114 The small lung volumes mean that airways are narrower than normal and more likely to be occluded by secretions, thereby predisposing the patient to recurrent pneumonia and hypoxemia due to atelectasis and ventilation-perfusion mismatch. Related spinal cord compres-sion can also cause respiratory muscle weakness and “pump” failure.
Despite the 10% of infants and young children with these complications, most patients with achondroplasia survive into adulthood. In contrast to the heterozygous mutation causing achondroplasia as an autosomal dominant trait, the skeletal abnormalities of homozygous offspring are so severe that most die in the fi rst year or two of life.
Two other heterozygous mutations in the FGFR3 gene account for the fi ndings in thanatophoric dysplasia, which, like homozygous achondroplasia, is lethal in very early life. These are the most severe phenotypes caused by mutations in the FGFR3 gene; achondroplasia is less severe and hypo-chondroplasia (HCH) is the least severe. 115
Jeune syndrome, or asphyxiating thoracic dystrophy, is a rare autosomal recessive abnormality of endochondral bone formation characterized by a very small, shallow thoracic
cage, abnormalities of the pelvis, polydactyly, and abnormal teeth. The thoracic cage does not grow normally, with ribs having a very low radius of curvature that produce a poorly compliant thorax that can only expand caudally during respi-ration (Fig. 66-10A). Without intervention, severe respira-tory failure occurs and patients can die early in life. 116 There is the additional mechanical disadvantage of a fl at low dia-phragm with a lower force generating capacity due to the increased radius of curvature. In a 4-month-old child who died with Jeune syndrome, pathologic examination showed that there was a normal complement of preacinar arterioles, airways, and minimal impact on alveolar growth; however, there was evidence of vascular remodeling consistent with pulmonary hypertension. 117
There are a number of different surgical interventions that are available to correct the thoracic limitation from Jeune syndrome, and both involve lateral expansion.
In one procedure, a vertical expandable prosthetic tita-nium rib (VEPTR) is placed across a thoracotomy and a series of sequential osteotomies made through the middle ribs. The VEPTR has a radius of curvature much smaller than the rib-cage and when the freed ribs are sutured in place, they are moved outward from their original position (see Fig. 66-10). In time, the thoracic cage heals, with a greater thoracic cross-sectional area shown on chest CT scan (Dr. Robert Campbell, personal communication).
A separate technique, lateral thoracic expansion, 118 also uses a thoracotomy with sequential osteotomies and lateral expansion. The osteotomies are offset from each other and the periosteum is left in place and the “long” ends of adjacent ribs are attached using titanium supports for reinforcement (Fig. 66-11A). This expands the chest outward and leaves large gaps at every other rib level; however, within 3 weeks postoperatively, there is evidence of bone growth from the periosteum (Fig. 66-11B). Both techniques have been used successfully over the last decade.
Osteogenesis imperfecta, an inherited disorder of bone formation, usually results from mutations in the genes encod-ing type I collagen. It is associated with fractures of the bones including the ribs. The common respiratory problems relate to the fractures of the ribs produced by minimal trauma. This may cause a rapid-shallow breathing pattern, because deeper breaths are painful. The infl ammatory response to fractures may cause febrile episodes that clinically are diffi cult to dis-tinguish from respiratory tract infections but will increase the metabolic demand on the patient. Chest radiographs are often of no help in defi ning absence or presence of infi ltrates because the lung parenchyma is obscured by bone and callus formation.
Jarcho-Levin, or spondylothoracic dysplasia, syndrome is an autosomal recessive disorder in which there is a combina-tion of spinal and rib cage abnormality with truncation of normal spinal growth and a fan-shaped appearance of the ribs (Fig. 66-12). The abnormality begins with the spine, with multiple vertebral anomalies at all levels with hemivertebrae, and fused, hypoplastic vertebrae. 119 Because of the restric-tive thorax, patients with Jarcho-Levin syndrome can experi-ence chronic respiratory failure early in life. In one series, mortality was 44% by 6 months of age. 119 In addition, there also can be secondary pulmonary hypertension and congestive heart failure. Although death can occur during infancy, in a
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A BFigure 66-10 Jeune syndrome before (A) and after (B) repair using bilateral lateral expansion using the VEPTR. (Courtesy of Dr. Randall Betz.)
A BFigure 66-11 A, Jeune syndrome with repair using the lateral thoracic expansion technique, with titanium supports, immediately after initial repair, with black arrows indicating rib ends from osteotomy. B, After 3 weeks with evidence of ossifi cation of periosteum at rib ends. (Reprinted with permission from Davis JT, et al: Ann Thorac Surg 77:445-448, 2004.)
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Puerto Rican cohort those who survived infancy had an almost 3-fold decrease in hospitalizations for respiratory tract infec-tions after 24 months of age. 119
Surgical interventions to treat the thorax of patients with Jarcho-Levin syndrome are similar to those for Jeune syn-drome and may prevent the need for or complement ventila-tory support. Anterior and/or posterior spinal fusion have been performed in patients with progressive scoliosis. 120 In other situations, lateral thoracic reconstruction has been per-formed. 121 Chest wall expansion using VEPTR has been per-formed in two general patterns: lateral rib-to-rib chest wall distraction using the VEPTR after a series of thoracotomies and osteotomies to open the medial bone mass or with a rib-to-spine or rib-to-iliac crest traction spanning the defective region if there is signifi cant scoliosis (Dr. Robert Campbell, personal communication). Outside of stabilization from the initial surgery, subsequent expansions to maintain traction on the spine can encourage spine growth.
Pectus Excavatum
Pectus deformities are among the most common abnormali-ties of the thorax. There are no recent data on incidence; however, in older data the incidence was 6 to 8 per 1000 children. 122 Although the causes of pectus are not clearly defi ned, they may be linked to upper airway obstruction during chest wall growth, overgrowth of costal cartilage, tho-racic cage muscle weakness, and underlying mesenchymal abnormalities, such as connective tissue disease. 123 If pectus
excavatum is discovered, a comprehensive patient and family history and physical examination should be performed to evaluate for other associated disease processes such as other skeletal abnormalities, mitral valve prolapse, and Marfan syndrome.
The nature and extent of physiologic abnormalities associ-ated with pectus deformities are controversial. 124,125 There have been studies demonstrating that pectus excavatum pro-duces no pulmonary function abnormalities, 126 whereas others demonstrated a mild to moderate restrictive defect, 122,127 which correlates only loosely in severity to radiographic measurements of the magnitude of the pectus. However, others have demonstrated that though restrictive defects occur, they are less common than obstructive defects. 128-130
There are two basic approaches to pectus excavatum surgi-cal correction. The fi rst is the classic Ravitch procedure that involves a sternotomy and bone resection with remodeling of sternal cartilage. 131 In a minority of patients receiving the Ravitch procedure, there was a signifi cant asphyxiating restrictive defect that occurred in the years postopera-tively, 131,132 and alterations were made to correct this defect and minimize the occurrence. 131,133 The second is the Nuss procedure in which a titanium bar, bent to the expected contour of the chest after surgery, is inserted beneath the ribs laterally and rotated anteriorly to apply outward pressure on the internal edge of the sternum. 134 The bar remains in place for 2 to 4 years and the sternal remodeling remains perma-nent in most cases. 135
A
B
Figure 66-12 Jarcho-Levin syndrome on PA view (A) and on chest CT scan reconstruction (B) demonstrating the shortened thorax and “fan-shaped” orientation of the ribs relative to the spine. (Courtesy of Dr. Randall Betz.)
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There is wide variation in pulmonary outcomes after cor-rective surgery. In some patients, there is actually a decrease in lung function after surgery. 131,132 This has been related to the severity of the pectus, with the less severe patients having less improvement or a decrease in lung function. 135 The group that developed the Nuss procedure has outcome data in a cohort of 43 patients that demonstrated a statistically signifi cant improvement of 5% of predicted value in FVC and FEV1 and of 8% in FEF25-75% after the bar was removed at a mean of 2.9 years after insertion. 135 Interestingly, the patients who were under 11 years of age had no signifi cant improve-ment in pulmonary function, whereas the patients over age 11 all had signifi cant improvement. 135 There is increased oxygen consumption at high levels of exercise before and after pectus repair, although the improvement in exercise capacity after pectus repair appears to be modest. 126
For the vast majority of subjects who receive pectus repair there is minimal cardiac dysfunction. 136,137 However, there is some evidence for increased stroke volume after repair, increased ventricular fi lling, increased oxygen pulse resulting in a decreased heart rate at the same workload, and increased duration and level of exercise. 136,138
Scoliosis
In the United States, approximately 1 in 1000 persons has a scoliotic curve greater than 35 degrees and 1 of 10,000 has a curve greater than 75 degrees, which can put them at risk for chronic respiratory failure. 139,140 This places about 30,000 patients at risk for chronic respiratory failure caused by sco-liosis in the United States. 139 Patients with infantile or juve-nile scoliosis typically have greater morbidity and mortality compared with patients with adolescent onset scoliosis, who can have very little morbidity if the degree is mild and/or it is detected early. 141,142 Therefore, early diagnosis and aggres-sive intervention are critically important.
There are a number of different causes of scoliosis. Although scoliosis is visualized on examination or on radio-graph as a spinal curvature, it goes well beyond just the spine. The scoliosis can be a primary spinal defect with hemiverte-bra and fused or absent vertebra that alters the normal spinal growth pattern. Alternately, the curve can be secondary to lateral rib tethering from rib fusion (Fig. 66-13A-C) or to rib absence (Fig. 66-13A,B) with inadequate lateral support. With rib fusion, the contralateral spine grows at a faster rate than the ipsilateral spine and the curve increases with growth (Fig. 66-13C). Absence of ribs causes an incompetent thorax with adequate support on only one side, and with growth, there is a curve convex to the side with the rib absence (Fig. 66-13A,B). Patients with intercostal muscle weakness can develop scoliosis due to inadequate ribcage support with scoliosis and a more downward rotation of the ribs in a “Christmas tree” appearance, as is seen in spinal muscular atrophy (Fig. 66-14).
Scoliosis can cause a restrictive defect in which the mag-nitude of the restriction is related to the angle of scoliosis (Cobb angle), the location of the curve, and loss of normal thoracic kyphosis. Although the amount of the curve can be linked to respiratory compromise, the correlation is not direct or consistent. The level of curve and the amount of spinal rotation are also important in determining the amount of
respiratory compromise. The more cephalad the curve, the more severely the lung on the convex side is compressed. Spinal rotation shifts the ribs laterally so that the midpoint of the sternum is lateral to the midpoint of the spine (Fig. 66-15). This further compresses or distorts the lungs by fl attening them in the lateral plane and puts torsion on the diaphragm. 143 The torsion on the diaphragm may increase the radius of curvature of the diaphragm, thereby decreasing the force-generating capacity and making it less effi cient.
The compliance of the respiratory system and, in particu-lar, the chest wall is decreased in patients with scoliosis. This decrease in compliance correlates closely with the severity of scoliosis and with the decrease in FVC 140 that is well described in scoliosis. In addition, as might be expected in the convex lung, there can be peripheral airway obstruction and air trap-ping, 140,144 demonstrated by plethysmography; as one might expect, this has not been consistently demonstrated using the helium dilution technique. Some patients have demonstrated a signifi cant postbronchodilator decrease in the RV/TLC ratio and an increase in FEV1, which was thought to indicate increased airway smooth muscle tone to resist the compres-sive force from the scoliosis 144 ; however, airway hyperreac-tivity was not independently assessed.
Scoliosis in certain circumstances can have a profound infl uence on lung development. Congenital scoliosis that is allowed to progress and signifi cantly limit lung growth within the fi rst few years of life can impact lung growth during the period of rapid alveolar development and limit alveolar number, although the alveolar size is appropriate for age. 145
There are a number of different ways to intervene in treat-ing children with congenital scoliosis. In milder cases, bracing may prevent or decrease progression of the curve through adolescence, after which time further progression should be minimal. For more severe cases, it is generally accepted that spinal fusion using instrumentation such as Harrington rods is the most reliable fi nal solution in that it stabilizes the spine well with some correction and prevents further progression. The disadvantage of spinal fusion is the lack of potential for future growth of the fused segment, which limits its utility in younger patients.
There are two alternate methods of spinal correction that allow for spinal growth: “growing rods” and the vertical expandable prosthetic titanium rib (VEPTR). Growing rods are placed along the lateral edges of the spinal column and attached intermittently along the stabilized region (Fig. 66-16). As the patient grows, the rods can be lengthened at the connection points or replaced with longer rods to allow normal spinal growth. Whereas some believe that the advan-tage of this construct is that it prevents any limitation of the outward ribcage motion during respiration and keeps the correction in the perispinal region, others believe that invad-ing the perispinal region makes the defi nitive spinal fusion performed later more diffi cult.
The VEPTR has been used in patients with congenital scoliosis with rib fusion or rib absence (see Fig. 66-13B). The advantage of use in these two situations is that there is both correction of the curve, to the extent possible, and rib cage stabilization. Semiannually, the VEPTR is expanded to allow normal growth. Although some have expressed concern that the placement across multiple ribs will decrease rib cage
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A
B
C
Figure 66-13 Absence of ribs 2 through 7 and fusion of ribs 8 and 9 (arrow) in a 1-week-old girl (A) and later at 10 months (B), demonstrating scoliocurve of 50 degrees. (Courtesy of Dr. John Flynn.) C, Rib fusion and scoliosis in a different 5-year-old girl. (Courtesy of Dr. Randall Betz.)
compliance and negatively impact respiration, there is no evidence to support this assertion. Importantly, there is minimal, if any, entry into the perispinal region that is thought to make any subsequent spinal fusion after growth has ceased much easier (Dr. Robert Campbell, personal communica-tion). Unfortunately, there is a paucity of pulmonary function outcome data after insertion using either the growing rod or VEPTR.
Considerable controversy still exists over whether Har-rington instrumentation improves lung function. A meta-analysis of 173 patients indicated a signifi cant improvement of 2% to 11%. 146 The improvement may not be immediate, and there may be initial loss of vital capacity; however, the preoperative FVC is reached by 2-year follow-up. 147,148 Much of the variability in improvement in lung function may depend
on at what point the intervention is performed. If performed after the curve is not correctible with traction, the likelihood of signifi cant improvement is minimal; however, the patient may still benefi t from preventing further progression of sco-liosis and restriction.
Defects in Development of the Chest Wall Muscles
The chest wall is considered broadly as the respiratory pump and the structures bordering on the lungs, including the thorax, both inspiratory and expiratory musculature, and the abdominal wall. Congenital defects in the structure of the chest wall muscles can affect the function of the respiratory pump and the development of the lung.
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Figure 66-14 A chest radiograph of patient with spinal muscular atrophy type 1 (Werdnig-Hoffman disease) demonstrating the caudal collapse of the ribs due to intercostal muscle weakness. (Courtesy of Dr. Randall Betz.)
A
BFigure 66-15 Chest CT scans at 2 years (A) and 7 years (B) of age demonstrating the progression of spinal rotation. (Courtesy of Dr. Robert Campbell.)
Congenital Diaphragmatic Hernia
Congenital diaphragmatic hernia (CDH) occurs in approxi-mately 1 in 2500 live births, 149-151 and about 40% are associ-ated with other congenital abnormalities (Table 66-3), including neural tube defects, cardiac anomalies, and skeletal, craniofacial, urinary, anterior abdominal wall, and other defects that may infl uence survival. 152,153 Of the 60% without other major congenital malformation, the magnitude of the pulmonary hypoplasia strongly infl uences survival.
The hernia defect is caused by a failure of the pleuroperi-toneal canal to close during fetal development. Although the pulmonary hypoplasia has been attributed to mechanical compression from the herniated abdominal content, recent evidence suggests that there are a number of mesenchymal growth factors and signaling pathways that may be affected during diaphragm development. 154 These are believed to cause the abnormal branching pattern, which can leave the lung in the late canalicular or early saccular stage of develop-ment. 155 In fact, the contralateral lung itself is also smaller than normal. 155
A number of investigators have studied lung function in school-age survivors of CDH. The data are remarkably con-sistent and demonstrate mild airway obstruction, normal total lung capacity, and some increase in RV/TLC ratios. 156-163 Although MIP is decreased (as would be expected), MEP is not signifi cantly different from normal. 164 Of the fl ow mea-surements, FEF25-75% is decreased proportionally to the perfu-sion defect 164 that probably refl ects the developmental truncation of the vascular and airway tree. There is also bronchodilator sensitivity that may be due to the increased smooth muscle in the airways and small airway disease as part
of the initial abnormality or as an iatrogenic effect from the early interventions and medical course. 164
The status of the thoracic structures and the thoracic pump has not been extensively investigated. In one study of 25 subjects, there was a 46% incidence of pectus deformities and scoliosis. 164
ABDOMINAL WALL DEFECTS (GASTROSCHISIS, OMPHALOCELE, PRUNE-BELLY SYNDROME)The anterior abdominal wall is part of the respiratory muscle pump, and abdominal wall defects have potential infl uences on the developing lung. Omphalocele and gastroschisis occur in approximately 1 in 4000 to 5000 live-born children. 165 Prune-belly or Eagle-Barrett syndrome is less common and has absent or reduced abdominal wall musculature believed to be due to obstruction of the urinary outfl ow tract and
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Figure 66-16 Bilateral growing rods. (Courtesy of Dr. Randall Betz.)
massive distention of the urinary tract and abdomen and abnormal mesenchymal development. Because of the increased abdominal compliance, these defects allow abdomi-nal contents to extend beyond the usual borders of the ante-rior abdominal wall.
Mechanically, two problems can occur. With diaphragm contraction during inspiration, the abdominal contents will go outward more instead of serving as a “fulcrum” moving out the inferior rib cage. During forceful exhalation, there is less abdominal force generated to augment the passive recoil of the ribcage and maneuvers like coughing can be signifi -cantly compromised. In this situation, an abdominal binder can be useful.
Prune-belly syndrome presents a number of additional respiratory challenges. Some of these patients have general-ized muscle weakness related to uremia and to corticoste-roids administered following renal transplantation. As a result of the mechanical abnormalities, these patients have slightly reduced lung volumes, markedly reduced inspiratory and expiratory muscle strength, and impairment in exercise capacity. 166,167 The exercise impairment may be due to the marked thoracoabdominal asynchrony that occurs during
exercise and may be related to abnormally large ribcage excursion during exercise. 166 Interpretation of tests of airway obstruction in these patients is diffi cult because expiratory muscle weakness probably contributes to reduced expiratory fl ow rates, particularly peak fl ow.
Patients with abdominal wall defects can have narrow chest walls, downslanting ribs, and reduced radiographic estimates of lung volume, suggesting a component of pulmo-nary hypoplasia. In fact, the radial alveolar count, an index of alveolar number, is reduced in children with giant ompha-loceles as can be the lung weight–to–body weight ratio. 168
Closure of abdominal wall defects presents both respira-tory and cardiovascular challenges. Although the size of the entire coeloemic cavity has not been estimated in these conditions, the peritoneal cavity is thought to be small. Thus, when the defect is closed, abdominal pressure increases. This can be an advantage to the infant in that increased abdominal pressure may elevate and lengthen the diaphragm and decrease the radius of curvature, which puts the dia-phragm at a more favorable length-tension relationship. Most artifi cial materials used to close the wall are nondistensible and skin is often under tension. Inspiration in these patients may be associated with large positive swings in intra-abdomi-nal pressure, which may prevent venous return to the right side of the heart, compress the inferior vena cava, and impair cardiac output.
Lung function has been measured in some infants before and after surgical closure of abdominal wall defects. Lung volumes as measured by a forced defl ation vital capacity maneuver were decreased by about 40%, and compliance of the respiratory system was reduced by about 50%, as might be expected. 169,170 In 18 adolescent patients who had a large omphalocele (>6 cm) or gastroschisis (>4 cm) repaired at birth, there was no abnormality in FVC or in cardiovascular function during exercise. 167 However, they reached their maximal heart rate sooner into exercise and had a lower maximal oxygen consumption than normal controls, 167 both of which were thought to be due to deconditioning.
NEUROMUSCULAR DISEASE
Classifi cation of Neuromuscular Diseases
Although there are a wide variety of neuromuscular condi-tions with many different genetic and cellular etiologies, they are often unifi ed by a morbidity and mortality due to respira-tory failure (Table 66-4). This can result either from progres-sive chronic respiratory failure or from an acute event rapidly overwhelming the capacity of the respiratory system. Outside of the direct failure of the diaphragm or chest wall muscles, upper airway muscle failure, in particular the pharyngeal and laryngeal muscles, can also worsen respiratory dysfunc-tion. Pharyngeal muscle weakness can lead to upper airway obstruction. The weakness can be exacerbated during sleep and add resistive load to the respiratory system. Laryn-geal muscle weakness can decrease airway protection and put a patient at greater risk of aspiration. In addition, failure of the intercostal muscles can decrease thoracic support and cause a downward “collapse” of the ribs in a “Christmas tree” appearance (see Fig. 66-14), as in spinal muscular atrophy, or can lead to scoliosis if the weakness is asymmetric.
Data from Slavotinek AM: Fryns syndrome: A review of the phenotype and diagnostic guidelines. Am J Med Genet 124A:427-433, 2004; Schinzel A: Tetrasomy 12p (Pallister-Killian
syndrome). J Med Genet 28:122-125, 1991; Gripp KW, Donnai D, Clericuzio CL, et al: Diaphragmatic hernia-exomphalos-hypertelorism syndrome: A new case and further evidence of
autosomal recessive inheritance. Am J Med Genet 68:441-444, 1997; Neri G, Gurrieri F, Zanni G, et al: Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome. Am J
Med Genet 79:279-283, 1998; Tachdjian G, Fondacci C, Tapia S, et al: The Wolf-Hirschhorn syndrome in fetuses. Clin Genet 42:281-287, 1992; Wieland I, Jakubiczka S, Muschke P,
et al: Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet 74:1209-1215, 2004; Jelsema RD, Isada NB, Kazzi NJ, et al: Prenatal diagnosis of congenital
diaphragmatic hernia not amenable to prenatal or neonatal repair: Brachmann-de Lange syndrome. Am J Med Genet 47:1022-1023, 1993; and Wilkie AOM, Slaney SF, Oldridge M,
et al: Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 9:165-172, 1995.
Additional references: http://www.geneclinics.org and http://www.ncbi.nlm.nih.gov.
Both thoracic defects will further add to the load on the respiratory system.
Neuromuscular disease can be localized anywhere from the corticospinal tract to the peripheral nervous system and the myoneural junction to the muscle itself.
The effects on the respiratory tract depend not only on the nature and location of the abnormality but also on whether it is acute or chronic. In general, lower motor neuron, myopathic lesions, and acute neurologic illness cause fl accid muscles and poor chest wall stabilization. However, upper motor neuron or cortical lesions and chronic neurologic illness often increase muscle tone and cause less mobile chest wall ligaments and joints. Although this stiffness can be treated or prevented to an extent with aggressive physical therapy to maintain range of motion, pharmacologic therapy with muscle relaxants is a common adjunct.
Spinal cord trauma is one example of the importance of lesion location. The respiratory effects of low thoracic cord lesions are minimal, although cough and forced expiratory maneuvers that rely on activation of abdominal wall muscles may be impaired. In high thoracic cord lesions, intercostal muscles are affected, causing breathing to be purely from the diaphragm. High cervical cord lesions (C3-5) affect the intercostal muscles and the phrenic nerve and diaphragm; therefore, patients with these lesions cannot breathe independently.
Pathophysiology
ALTERATIONS OF LUNG FUNCTION IN NEUROMUSCULAR DISEASETotal lung capacity (TLC) and vital capacity (VC) may be normal in mild neuromuscular disease but are reduced in moderate to severe disease. The reductions in TLC and VC are caused by inspiratory and expiratory muscle weakness, scoliosis, and decreased lung and chest wall compliance due to a progressive decrease in lung and chest wall expansion. 169 RV may be normal or elevated as a result of expiratory muscle weakness. Therefore, an elevated RV/TLC ratio in patients with neuromuscular disease is not usually due to air trapping as is the case in obstructive lung disease.
Maximal expiratory fl ow rates in patients with neuromus-cular disease are usually diminished as a consequence of both low lung volumes and decreased expiratory muscle strength, because both lung volume and driving force can impact maximal fl ow. Furthermore, patients with neuromuscular disease often have a characteristic shape of the fl ow-volume curve at low lung volumes, with a precipitous decrease in fl ows before reaching RV 171 rather than a linear decrease through lower lung volumes. This phenomenon is a result of the diminished ability of the expiratory muscles to overcome the outward recoil of the chest wall. As is the case in most
Types 0-IV Progressive muscle weakness, onset from prenatal to adulthood
Autosomal recessive SMN1 (SMN2 dosages impacts on type)
95% homozygous partial gene deletions; 5% compound heterozygote for deletion and point mutation
Additional references: http://www.geneclinics.org and http://www.ncbi.nlm.nih.gov.
restrictive lung disease, the FEV1/FVC ratio is normal in patients with neuromuscular disease.
Lung compliance is reduced in patients with neuromus-cular disease, 172 whereas specifi c compliance is usually normal. 173 This suggests that the decreased compliance is due to loss of lung units or alveolar number as opposed to an alteration of the tissue properties of the lung.
RESPIRATORY MUSCLE STRENGTHMaximal inspiratory and expiratory pressures are reduced in patients with neuromuscular disease. 169,174,175 The degree of reduction does not seem to correlate with the reduction in general skeletal muscle strength. 174 Respiratory muscle strength is related, however, to the distribution of general muscle weakness, tending to be more severe in patients with proximal muscle weakness and less severe in patients with mainly peripheral muscle weakness. 171
CHEST WALL ALTERATIONSInfants and young children with neuromuscular disease often have a highly compliant chest wall, 176 although most adults with neuromuscular disease will have reduced chest wall compliance. 174 This suggests that intact muscle function is necessary for the development of normal intrinsic chest wall stiffness but that, with time, long-term diminished tidal chest wall excursions lead to costovertebral joint contractures and poor chest wall compliance.
CONTROL OF BREATHINGPatients with neuromuscular disease may have abnormalities of the respiratory control center as a primary or secondary event. Clearly, brainstem abnormalities can directly affect respiratory control and cause diminished ventilatory responses to hypercarbia and hypoxia, central and obstructive apnea, and excessive periodic breathing. As is the case with chronic lung disease of any sort, long-standing CO2 retention can reset the respiratory control center to a higher CO2 level
and diminish the hypercarbic response. Furthermore, the chronic metabolic alkalosis compensating for long-standing CO2 retention can blunt respiratory drive in response to increasing CO2 levels by buffering hydrogen ion and reducing acidosis.
Whether patients with neuromuscular disease that is not of central origin, such as myopathies, have disordered control of breathing is diffi cult to ascertain, because most tests of respiratory control depend on intact respiratory system mechanics and muscle strength. For example, assessing the change in minute ventilation during CO2 rebreathing assumes that such ventilatory changes are not limited by the mechan-ics of the system, an assumption that is not true in the pres-ence of severe restrictive chest wall disease and muscle weakness. To overcome this limitation, the P100 has been sug-gested as a good index of respiratory drive in patients with lung mechanic abnormalities. By assessing the mouth pres-sure response to the fi rst 100 milliseconds of an inspiratory occlusion, patients with neuromuscular disease can presum-ably reach normal values despite respiratory muscle weakness because the normal value of P100 (about 2 cm H2O in adults) is well below the maximal pressures that can be generated by most patients with neuromuscular disease. Although few studies have been reported, it appears the patients with neuromuscular disease have normal P100 values, indicating intact respiratory drive. 177,178
ABNORMALITIES OF COUGH IN PATIENTS WITH NEUROMUSCULAR DISEASEA major factor predisposing to recurrent pneumonia in patients with neuromuscular disease is an ineffective cough due to weak inspiratory muscles, poor glottic closure, and weak abdominal and thoracic expiratory muscles. Patients with low thoracolumbar cord lesions and paraplegia can still maintain a fairly effective cough because of intact abdominal muscle strength. Patients with tetraplegia can use the clavicu-lar head of the pectoralis major as a muscle of forced expira-
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tion and often unconsciously adopt these muscles for coughing. 179
Approach to the Patient with Neuromuscular Disease
In taking a history from a patient with neuromuscular disease, it is important to ask about chronic or recurrent pneumonias, gastroesophageal refl ux, aspiration of secretions, snoring, and symptoms of sleep hypoventilation and obstructive sleep apnea such as morning headaches and daytime somnolence. Seizure control is important because uncontrolled seizures may predispose to aspiration pneumonias.
On physical examination, the spine should be carefully assessed for scoliosis as a possible contributing cause to lung dysfunction. Signs of cor pulmonale should be evaluated and the patient should be examined for clubbing as an indication of bronchiectasis from recurrent suppurative lung infections.
Pulmonary function tests including lung volumes and maximal inspiratory and expiratsory pressures should be per-formed on all patients who can do them. Chest radiographs and assessment of oxygenation and ventilation by arterial blood gas analysis, pulse oximetry, end tidal CO2 measure-ment, and serum bicarbonate (as an index of the chronic CO2 retention) should be done. A modifi ed barium swallow, with a feeding specialist, to evaluate swallowing function and gas-trointestinal anatomy and gastroesophageal refl ux studies (scintiscan or pH probe) should be done in patients with histories suggestive of aspiration. Sleeping pulse oximetry or more formal polysomnography should be done in patients with histories suggestive of sleep apnea or in those at risk of sleep hypoventilation by virtue of marginal lung function (VC less than 50%, FEV1 less than 40% of predicted). This can be a very valuable screening tool since the compensatory mecha-nisms that patients with neuromuscular disease develop to overcome their mechanical abnormalities may not be present or will be compromised during REM sleep. Electrocardiogra-phy and echocardiography should be done in all patients with baseline or sleeping hypoxemia to evaluate for the presence of cor pulmonale.
Respiratory Complications of Neuromuscular Disease and Their Treatments
POOR AIRWAY CLEARANCEPoor lower airway clearance due to an ineffective cough puts patients with neuromuscular disease at increased risk of pneumonia. Once secretions have entered the lower respira-tory tract, many patients are unable to clear them effectively and lower respiratory tract infections occur. In addition to standard airway clearance therapy with manual percussion with postural drainage and oropharyngeal suctioning, there are a number of other assisted airway clearance therapies available to compensate for inadequate cough.
A cough involves a deep inspiration, with a brief glottic closure during early exhalation, followed by glottic opening with explosive expiratory fl ow. 180 Each of these three phases can be abnormal in patients with neuromuscular disease.
Inspiration can be augmented by breath stacking with a mask with a one-way valve, glossopharyngeal breathing,
manual insuffl ation, and using a mechanical insuffl ator. 181-183 This will increase elastic recoil pressure that can be used to augment exhalation.
There is no way to recreate the effect of glottic closure in patients with bulbar dysfunction or pharyngeal weakness.
Exhalation can be augmented manually with abdominal thrusts or compressions 78 or by applying negative pressure at the airway opening using a mechanical exsuffl ator. 182-184 Manual cough assistance can be challenging in patients with scoliosis or extremity contractures that can block access to the abdomen. 184 Exsuffl ation pressures above −40 cm H2O may cause upper airway narrowing, especially in the younger patient or those with pharyngeal hypotonia. Together, mechanical insuffl ation and exhalation has been used success-fully with pressures of up to +40 cm H2O for insuffl ation and −50 cm H2O for exsuffl ation in pediatric patients with neu-romuscular disease. 185 Mechanical insuffl ation and exsuffl a-tion can be delivered through a mouthpiece, face mask, or endotracheal or tracheostomy tube, depending on the patient’s situation.
Other alternatives to improve peripheral airway clearance include high-frequency chest wall oscillation (HFCWO) and intrapulmonary percussive ventilation (IPV). HFCWO is commonly used in patients with cystic fi brosis to decrease the viscosity of mucus and to shear it from airway walls, while the patient expels it with a cough or deep breathing maneu-ver. Although the inadequate cough in a patient with neuro-muscular disease may limit its utility in this population, it has been successfully used in patients with quadriplegic cerebral palsy. 186
IPV delivers small pulses of air at high frequency and vari-able pressures, with an aerosolized solution with saline or a bronchodilator delivered at the same time. IPV has been used successfully in pediatric patients with a variety of different neuromuscular conditions irrespective of their ability to cough. 56,187-189
RECURRENT PNEUMONIARecurrent pneumonias are a common cause of morbidity in patients with neuromuscular disease. Other risk factors include aspiration due to excessive secretions, poor laryngeal-pharyngeal clearance, poor recognition, and poor airways clearance. Patients with a signifi cant central nervous system dysfunction may have hypersalivation and be unable to prop-erly recognize and clear upper airway secretions. Therefore, there can be an unfortunate combination of excessive volume and ineffective clearance that puts one at risk of aspiration.
Antibiotic coverage should include anaerobic oropharyn-geal organisms in addition to gram-positive organisms (clinda-mycin, amoxicillin-clavulanic acid). For patients with a history of prolonged endotracheal intubation or tracheostomy, current or previous, coverage for Pseudomonas aeruginosa should be added. Finally, patients with neuromuscular disease are also susceptible to community-acquired organisms. For patients with recurrent aspiration, antibiotics to treat common anaer-obic mouth organisms can be given either intermittently or prophylactically to prevent aspiration pneumonia.
In addition to antibiotic therapy appropriate to known or suspected pathogen, patients should get augmented airway clearance via manual chest physiotherapy or a raised volume device such as an intermittent positive breathing device or a
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cough assistance device. These therapies can be used both on a prophylactic basis and in an acute care setting. Mucolytic agents such as dornase-α, hypertonic saline (3% or 6%), and acetylcysteine have been used clinically to help clear thick mucus in patients with recurrent or chronic pneumonia.
Inhaled β-agonist bronchodilators are of questionable utility in patients with neuromuscular disease without a coin-cident history of asthma, but they may be useful in combina-tion with chest physical therapy, especially in the setting of acute atelectasis. They can also improve mucocilary clearance by increasing the ciliary beat frequency. CPAP or invasive or noninvasive mechanical ventilation can also be useful, both in compensating for the added load on the respiratory system from the infection and in augmenting airway clearance and providing distending pressure to maintain airway patency through a greater portion of the respiratory cycle.
SWALLOWING DYSFUNCTION AND GASTROESOPHAGEAL REFLUXAspiration is a major cause of recurrent pneumonia in patients with neuromuscular disease. Swallowing is a complicated mechanism involving precise timing between various pharyn-geal, laryngeal, and esophageal muscles. Damage to any of these muscles or the neural pathways that support them can have a major impact on swallowing function. In brainstem or cortical injury, there may be little or no swallowing function due to the absence of proper neural signaling and coordina-tion. With a more peripheral myopathy, swallowing dysfunc-tion may not occur until much later in disease progression; however, swallowing effi ciency may be impacted as patients have diffi culty safely taking in enough calories to meet their nutritional needs. 190
A speech therapy consultation may identify food textures that are not aspirated and modes of swallowing that can compensate for the abnormal swallow mechanism and can enable the patient to take at least part of his or her daily caloric intake by the oral route. 190 If this does not work, then a gastrostomy tube to bypass the oropharynx can be useful.
Although a tracheostomy tube with the cuff infl ated can bypass upper airway obstruction and provide a reliable inter-face for mechanical ventilation, it does not prevent aspiration. In fact, a tracheostomy can interfere with normal swallowing function and may increase the risk of aspiration, 191,192 perhaps by fi xing tracheal position and preventing closure of the airway by the epiglottis.
For a patient with or at risk of swallowing dysfunction, it is important to minimize the volume of secretions around the glottis. Upper airway secretions from rhinitis or sinus drain-age can be treated effectively with decongestant and antihis-tamine therapy. Hypersalivation can be treated effectively on a temporary basis with anticholinergic therapy using glycopy-rollate or scopolamine, 193,194 and botulinum toxin injections of specifi c salivary glands. 195,196 Salivary gland duct ligation and denervation can be used for patients in whom pharma-cotherapy has been ineffective, 197,198 but these procedures are irreversible. The risk of any of these interventions is overdrying secretions, which can put patients with tracheos-tomy tubes at higher risk of airway occlusion.
For reasons incompletely understood, the prevalence of gastroesophageal refl ux (GER) is higher in patients with neu-romuscular disease than in the general population. In patients
with cortical dysfunction, some have proposed a link between spasticity and increased intra-abdominal pressure exacerbat-ing GER, while esophageal dysmotility and decreased upper esophageal sphincter tone can also contribute. GER is treated with motility agents such as metoclopramide or bethanechol and antacids including both H2-receptor antagonists and proton pump inhibitors. If medical management fails, fundo-plication may be performed, although the success can be compromised in patients with seizure activity or tonic-clonic activity with intermittent increases in abdominal pressure. Fundoplication may also exacerbate swallowing dysfunction if the lower esophageal sphincter is wrapped too tightly.
RESPIRATORY FAILUREChronic respiratory failure is the hallmark and a unifying factor among the progressive neuromuscular disorders. The level of respiratory muscle fatigue in patients with neuromus-cular disease is the balance between respiratory muscle strength and the resistive and elastic load on the respiratory system. Fatigue occurs in patients with normal respiratory muscle strength when increased elastic or resistive respira-tory loads are great. In patients with neuromuscular disease, modestly increased elastic loads from scoliosis and chronic pulmonary fi brosis secondary to chronic aspiration, recurrent pneumonias, and other conditions may produce fatigue.
Nocturnal ventilatory support can enhance the quality of life in many patients with nighttime hypoxemia and hyper-carbia. Supplemental oxygen by nasal cannula may suffi ce in patients with hypoxemia caused by chronic lung disease without hypercarbia. The physiology of chronic respiratory muscle fatigue and its treatment with respiratory muscle rest are discussed earlier in this chapter.
Noninvasive ventilation has been used for over 60 years to treat chronic respiratory form neuromuscular disease. Although modern versions of the Drinker and Emerson tank ventilator “iron lung” are available today to provide negative pressure ventilation, negative pressure cannot be used in patients with upper airway obstruction. The vast majority of patients using noninvasive ventilation use positive pressure ventilation via nasal, oral, or oronasal interfaces. Although the available bilevel positive airway pressure units were originally developed for adult use, there are a number of interfaces that can be used effectively in pediatric patients.
Once the need for noninvasive ventilation extends well into the daytime hours, chronic invasive ventilation via tra-cheostomy tube can be useful. This is a decision that is predicated on a number of issues. The fi rst issue is how well the ventilator and interface is working for the patient. If the ventilator can adequately augment ventilation for a substan-tial portion of the day, and the skin underneath the interface remains intact, then there is no need to transition to invasive ventilation. However, with progression of the neuromuscular disease and/or decreased chest wall compliance, the nonin-vasive ventilator may not be able to assist ventilation with a high enough pressure to infl ate the lungs adequately. The fi nal, and perhaps most important, issue is the patient’s and family’s wishes. For many patients and family, invasive ven-tilation is an intervention that exceeds their own sense of propriety. Although for some families it is a value judgment, for others there may be a lack of understanding of what life with a tracheostomy means. With a properly sized tracheos-
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tomy tube, patients can still vocalize, and this can be improved substantially by using a speaking valve, which allows air in through the tracheostomy tube, but exhalation around the tracheostomy tube and between the vocal cords.
In chronic respiratory failure there is often a compensa-tory metabolic alkalosis. When the PCO2 is reduced by mechanical ventilation, chloride supplementation is often required in order to promote excretion of the retained HCO3
−.Acute respiratory failure usually occurs in the setting of
acute pneumonia or increased mucus plugging and atelectasis, causing hypoxic respiratory failure with ventilation perfusion mismatch. Because of this, it is critical to aggressively treat these episodes with increased airway clearance therapy, anti-biotics, and ventilatory support if indicated. Patients with marginally compensated respiratory muscle strength caused by underlying neuromuscular disease are also more likely to develop respiratory pump failure during an acute infection. Patients with general muscle weakness caused by myopathies often decompensate during intercurrent systemic illness, such as viral infections. The respiratory muscles are no excep-tion, and even nonpulmonary infections can lead to respira-tory failure in this setting.
COR PULMONALECor pulmonale is a common end-stage complication of neu-romuscular disease, and the genesis is multifactoral. An early sign of respiratory failure is nocturnal hypoxemia, which can cause pulmonary vasoconstriction and increased right heart strain. The severe scoliosis that can develop can cause restric-tive disease and a decreased FRC. The decreased FRC may decrease further during REM sleep, when intercostal muscle tone decreases. Prolonged periods of breathing at low FRC can cause airway closure and atelectasis, both of which result in hypoxemia from low V
./Q
. ratios due to airway closure and
a decreased surface area for diffusion. In addition, hypoven-tilation is common in neuromuscular disease. Furthermore,
the abnormal upper airway muscle control of patients with neuromuscular disease can lead to upper airway obstruction during sleep.
NUTRITIONAL STATUSBecause of swallowing ineffi ciency, maintaining an adequate daily intake of calories for growth can be diffi cult. The actual caloric need in patients with progressive neuromuscular disease is controversial, with some suggesting a basal meta-bolic need less than that of an age- and weight-matched child due to the relative lack of muscle mass and inactivity. The clear risk in not providing enough calories is weakening the muscles further by not meeting the basic metabolic needs, and running the risk of decreasing muscle mass further. Con-versely, an overweight child has the added burden of moving a heavier chest wall and fatiguing the respiratory muscles.
OTHER CONSIDERATIONSMany of the general principles of the care of patients with neuromuscular disease have been outlined in a recent Ameri-can Thoracic Society statement. 56 General supportive mea-sures should be stressed. Infl uenza vaccine should be given annually, and patients should receive all routine immuniza-tions, including Haemophilus infl uenzae vaccine, as well as pneumococcal vaccine. Giving the palivizumab vaccine for RSV prophylaxis remains controversial. Although there are not the same published data demonstrating effi cacy in reduc-ing the morbidity of RSV infection as with patients with bronchopulmonary dysplasia and congenital lung disease, many clinicians will use it in patients under 2 years of age with more severe conditions, such as SMA type 1 and nema-line rod myopathy. The enormous fi nancial and psychological burdens of patients with chronic progressive neuromuscular disorders and their families are best addressed by a multidis-ciplinary approach, with collaboration among the treating primary and subspecialty physicians, nurses, physical thera-pists, nutritionists, and social workers.
SELECTED READINGS
American Thoracic Society/European Respiratory Society: ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 166:518-624, 2002.
Estenne M, Heilporn A, Delhez L, et al: Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis 128:1002-1007, 1983.
Finder JD, Birnkrant D, Carl J, et al: Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am J Respir Crit Care Med 170:456-465, 2004.
Nuss D, Kelly RE Jr, Croitoru DP, Katz ME: A 10-year review of a minimally invasive technique for the correction of pectus exca-vatum. J Pediatr Surg 33:545-552, 1998.
Panitch HB: Airway clearance in children with neuromuscular weak-ness. Curr Opin Pediatr 18:277-281, 2006.
Wohl M, et al: Thoracic disorders in childhood. In Roussos C (ed): Lung Biology in Health and Disease: The Thorax. Part C: Disease. New York, Marcel Dekker, 1995, pp 2035-2070.
Wohl M, Griscom NT, Strieder DJ, et al: The lung following repair of congenital diaphragmatic hernia. J Pediatr 90:405-414, 1977.
REFERENCESThe references for this chapter can be found at www.pedrespmedtext.com.
