656
October 1978 The Journal o f P E D I A T R 1 C S
Surgical resection for pulmonary interstitial emphysema in the newborn infant Three patients with pulmonary interstitial emph).sema are presented in whom the course was similar and progressive. Eventually all three infants developed respiratory insu~ciency and chronic dependence on mechanical ventilation, cardiovascular complications of patent ductus arteriosus with congestive heart failure, and seizures probably secondary to intermittent periods of asphyxia and hypoxemia. All infants underwent Iobectomy and recovered rapidly. Follow-up examinations have shown some residual puhnonary abnormalities. A 11three infants are progressing within the normal range for motor development.
Charles R. Bauer, M.D.,* M. Jayne Brennan, P.N.P., Coleen Doyle, D.P.N.P., and Catherine A. Poole, M.D., M i a m i , Fla.
WITH THE ADVENT of sophisticated respiratory therapies adaptable to the very small, immature infant, the mortality from pulmonary insufficiency has been markedly reduced, but morbidity has increased as a result of complications o f these therapies. The "air block" syndrome (pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema, and even pneumoperitoneum) is beconling a common event in neonatal intensive care nurseries). 2 Three patients are presented in whom PIE occurred. The first followed a course consistent with an intrauterine ~,iral pneumonia, the second had a severe respiratory distress syndrome, and the third had massive aspiration of formula. All three infants required intubation and mechanical ventilation, ~Jeveloped PIE, and followed a progressive downhill course, with similar cardiovascular and neurologie complications. Because of respiratory dependence and worsening clinical findings, all three infants underwent pulmonary resection. The three infants survived the surgery, were eventually discharged, and have been followed for 10 to 13 months.
Front the Departments of Pediatrics and Radiolog); University of Miami School of Medicine. *Reprint address: Universityof Miami School of Medicine, Department of Pediatrics, P.O. Box 320875, 31iami, FL 33152.
Vol. 93, No. 4, pp. 656-661
CASE R E P O R T S Patient 1. This male infant was born at Jackson Memorial Hospital to a white, 24-year-old gravida 1 by emergency cesarean section because of a prolapsed cord. The pregnancy had been uncomplicated until eight days prior to delivery, when the membranes ruptured spontaneously. Abbreviations used BPD: bronchopulmonary dysplasia (N)CDAP: (nasal) continuous distending airway pressure CHF: congestive heart failure PDA: patent ductus arteriosus PIE: pulmonary interstitial emphysema RDS: respiratory distress syndrome The infant weighed 1,300 gm and was small for his estimated gestation, which by Dubowitz examination was 34 weeks. The Apgar score was 9 at i and at 5 minutes. On admission, the infant was in moderate respiratory distress and was treated with oxygen and nasal continuous distending airway "pressure. The initial chest radiograph demonstrated diffuse granularity and air trapping. The ifffant was treated with penicillin and gentamicin because of the prolonged rupture of membranes. His condition deteriorated rapidly over the first day, requiring intubation and mechanical ventilation. A pneumomediastinum developed and soon progressed to a pneumopericardium and left-sided pneumothorax, requiring drainage by thoracostomy. Seizures were observed on the second day ~/nd were treaied with phenobarbital. A right-sided tension pneumothorax developed on the third day, requiring drainage.
0022-3476/78/100656+06500.60/0 9 1978 The C. V. Mosby Co.
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Fig. 1.A, With re-expansion ofboth lungs follov,'ing the insertion ofthoracostomy tubes, numerous variably sized cystic collections of interstitial air were seen in the left upper lobe. The large rounded accumulation ofair superimposed on the cardiac silhouette was !oculated in the posterior mediastinum. I B, Progressive enlargement of the interstitial collections occurred, with collapse of the left lower lobe, mediastinal shift to the right, and severe compromise of the right lung. The right mainstem bronchus was selectively intubated, in an unsuccessful attempt tO decompress the left lung and re-expand the right lung. C, A follow-up examination of the chest at one year of age (10 t& months corrected)revealed residual chroni6 pulmonary changes on the fight side. The left lower lobe was well expanded and relatively clear. The heart was slightly enlarged, with elevation of the apex suggesting right ventricular hypertrophy.
Fig. 2.A, Diffuse pulmonary disease was present bilaterally. The right lower lobe was overexpanded, secondary to multiple variably sized cystic collections of interstitial air. B, Progressive enlargement of the cystic interstitial emphysema occurred, with severe mediastinal shift to the left, compromise of the entire left lung, and total atelectasis of 9the right middle and upper lobeS. C, Following surgical resectioh of the right lower lobe, the right middle and upper lobes re-expanded, and the mediastinal st/uctures returned to the midline. At 12 months of age (corrected), there were minimal chronic interstitial and pleural changes withslight overexpansion of the chest. The diagnosis of PIE in the left lung was first made after the tension was relieved and the lung re-expanded (Fig. I, A). After the chest tubes were removed, the PIE persisted with the formation of many large confluent cystic areas. 9 The fight mainstem bronchus was intubated for two days in an unsuccessful attempt to collapse the emphysematous left lung (Fig. 1, B). After the endotracheal tube was repositioned above the carina, a tension pneumothorax on the left recurred, again requiring the placement of a chest tube. The infant could not be weaned from - the respirator. On the eighteenth day of life, because the interstitial air and cysts were still present and the infant was dependent on a respirator, a left upper lobectomy was perfoz'med and ";vas tolerated very ,.,.'ell. Pathologic examination of the left upper lobe revealed an immature lung with chronic cystic interstitial emphysema and secondar~ patchy pulmonary collapse. Some interstitial fibrosis and marked giant cell reaction were also_ present.
Over the next two weeks, the infant was weaned slowly from the respirator. A patent ductus artefiosus and congestive heart failure briefly complicated the recovery, but were controlled by administration of digitalis and restriction of fluids. Another major complication was aphrenic nerve paralysis on the side of the surgery, which resulted in recurrent pulmonary atelectasis. The infant gradually improved over the next two months and was discharged on the seventy ninth day of life. The infant was seen in the follow-up clinic at corrected ages of 3, 6, and 10tAmonths, lie is developmentally within normal limits for both the Bayley and Denver Developmental tests, tie has had no major pulmonary problems and has tolerated mild Upper respiratory infections very well. Chest radiographs (Fig. 1, C) remain abnormal, but have shown sign!ficant improvement over the last year, with restoradan_ of diaphragmatic function. Patient 2. This male infant was born at an outlying hospital to a black, 21-year-old gravida 1 by a normal 7,'aginal delivery. The
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The Journal o f Pediatrics October 1978
Fig. 3.A, Diffuse bilateral pneumonia was secondary to aspiration. Within the left lung there were several cystic collections of interstitial emphysema. B, Progressive overexpansion of the left lung led to anterior herniation and mediastinal shift to the right. The right lung was compromised, but there had been partial resolution of the aspiration pneumonia. C, At 10 months of age, residual chronic pulmonary changes were present, though the left upper lobe and the entire fight lung were normally expanded.
pregnancy was uncomplicated until nine days prior to delivery, when the membranes ruptured spontaneously. The infant weighed 1,200 gm and was estimated by Dubowitz examination to be 30 weeks of gestation. The Apgar score was 2 at I and at 5 minutes. The infant '.vas intubated and given oxygen for approximately 5 minutes before spontaneous respirations were established. Because of continued respiratory distress, he ,,,,'as transferred to the Neonatal Intensive Care Unit at Jackson Memorial Hospital at age 4 hours. On admission, the infant was being ventilated with up to 95% inspired oxygen. The first chest radiograph showed diffuse haziness and was read as compatible with RDS. The infant was treated with penicillin and gentamicin because of the prolonged rupture of membranes, tle initially improved, but on the fourth day had generalized seizures followed by cardiorespiratory arrest. Bilateral pneumothoraees were demonstrated at this time, and were drained by thoracostomy tubes. A chest radiograph demonsrated bilateral PIE, pneumomediastinum, extra pleural air over the diaphragm, and a massive pneumoperitoneum. The chest tubes were removed within the next 48 hours, but the PIE pe~isted (Fig. 2, A). The process ofweaning from oxygen and the ventilator was complicated by the appearance o f a PDA and signs of CHF. The PIE persisted over the next two weeks, with carbon dioxide retention becoming a recurrent problem. By approximately one month of age, the infant was dependent on a respirator. His CttF was kept under control but he could not be adequately nourished because of restriction of fluid intake. The PIE had progressed to form large confluent cysts in the right lower lobe, which caused a marked mediastinal shift, collapse of the fight upper and middle lobes, and severe compromise of the left lung (Fig. 2, B). A fight lower lobectomy was performed on day 35 of age. Pathologic examination of the right lower lobe revealed severe interstitial emphysema with giant cell reaction and focal atelectasis. The infant did very '.,,'ell postoperaiively, and was weaned from the respirator within one week of surgery, tie was discharged on the eighty seventh day of life. The infant has been seen at corrected ages of 3, 6, and 12
months. Developmentally, he is within normal limits on the Denver and Bayley Developmental scales. His chest radiographs continue to show minimal interstitial changes (Fig. 2, C). He has been hospitalized once at age 9 months for an acute episode of wheezing, and wheezing has been a chronic problem. Patient 3. This male infant, the first of twins, was born to a black 20-year-old pfimigravida by normal vaginal delivery. The pregnancy had been uncomplicated until the day prior to admission, when the membranes ruptured spontaneously. The mother developed a fever of I01.6~ at which time blood cultures were done and antibiotic therapy was started at the local hospital, and she was transferred to Jackson Memorial tlospital for delivery. At delivery, the infant weighed, 1,110 gm and was estimated by Dubowitz examination to be approximately 30 weeks of gestation. Apgar scores were 2 and 6 at I and 5 minutes, respectively. The infant was intubated and given oxygen during transfer to the Neonatal Intensive Care Nursery. tte was treated with penicillin and gentamicin because of the prolonged rupture of membranes and maternal fever. The infant's initial chest radiograph was read as normal. Ite was quickly weaned to 25% inspired oxygen, but CDAP alone was unsuccessful because of persistent apnea. Aminophylline therapy controlled the apnea and the infant was then removed from the respirator and the CDAP. tie was transferred to Mr. Sinai Medical Center, a regional secondary care center, on the seventeenth day of life, weighing 1,240 gm and doing well. After approximately two weeks at Mr. Sinai Hospital, he had an episode of aspiration of formula and required intubation and mechanical ventilation. Ite was returned to the Neonatal Intensive Care Unit at Jackson Memorial Hospital, where the admis- . sion che.;t radiograph showed a pneumomediastinum and massive aspiration pneumonia. The infant had recurrent seizures, which were treated with phenobarbital. Mechanical ventilation at high peak pressures and high oxygen concentrations was required for a prolonged period of time. During the acute stage, a PDA ,,~ith CtlF occurred. This was treated medically by diuretics, digoxin, and restriction of fluids.
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By the fifth day after the aspiration, bilateral cystic changes compatible with PIE were seen on chest radiographs (Fig. 3, A). Respiratory distress and CHF were persistent. The trachea was extubated approximately two weeks after the aspiration but progressive emphysema of the left lung resulted in herniation across the mediastinum and secondary atelectasis of the right lung (Fig. 3, B). At 389 weeks postaspiration, his PDA and CHF were persistent and he had continued respiratory distress evidenced by retractions, wheezing, and poor feeding. At 4~Aweeks postaspiration (53 days of life), surgical intervention was considered, lndomethacin was used in an attempt to close the PDA but failed, and medical management was not successful in controlling the heart failure. The infant required reintubation. Intermittent episodes of seizure activity were treated with phenobarbital. While on the respirator, an attempt was made to selectively occlude the left bronchus and allow the compressed right lung to re-expand. Some re-expansion of the right lung occurred, but the left lung failed to decompress. The infant rapidly developed bradycardia and hypoxia. Two additional attempts to collapse the emphysematous left lung were similarly unsuccessful, with rapid clinical deterioration. The infant was examined by bronchoscopy at age 60 days and no intrinsic or extrinsic bronchial obstruction was seen. The PDA persisted, as did occasional seizures. At 78 days, a lung scan demonstrated markedly decreased perfusion to both the right lung, which was mostly collapsed, and to the large, emphysematous left lung. Severe apnea and bradycardia became more frequent. On day 95 of age, a left lower lobectomy and ligation of the PDA were performed. The left lower lobe was diffusely emphysematous, with minimal patchy focal atelectasis on pathologic examination. Postoperatively, the radiologic findings were improved but the mediastinal shift and PIE persisted in spite of the fact that the resected left lower lobe had been the most severely affected. He did well clinically and the trachea was extubated on the second postoperative day. tte subsequently developed a purulent pleural effusion which responded to systemic antibiotic therapy, but because of acute carbon dioxide retention, he again required mechanical ventilation. Seizures recurred with no evidence of meningitis. By one week postoperatively, day 103 of life, the infant no longer required ventilator), support and was feeding well. He was discharged on the one hundred thirtieth day of life (thirty fourth day postoperative). The infant was seen at corrected ages of 3, 6, 9, and 13 months. He is within the normal range in his developmental progress, llis respiratory status remains borderline. He has wheezing, rales and retractions, and some upper airway obstruction. He has had two upper respiratory infections but recovered without incident. His chest radiograph remains abnormal (Fig. 3, C). DISCUSSION Extra alveolar air, which is recognized as a major cau.se of mortality in the neonate,~ can seriously interfere with normal cardiovascular and/or pulmonary function. Large collections of air in the interstitial spaces can splint the lung, making normal respiration imposs!b!e. As air
Surgical resection for puhnonar), interstitial emph)'sema
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dissects along perivascular channels, blood vessels are compressed and pulmonary circulation is compromised. Macklin and Macklin ~ experimentally demonstrated the pathology of air escape in animals. They showed that pulmonary interstitial emphysema, pneumomediastinum, pneumothorax, pneumopericardium, subcutaneous emphysema, and pneumoperitoneum are all a part of a continumum of dissecting air, initiated by rupture of alveoli. This dissection process is not relieved until the cause of the increased pressure in the alveoli is relieved. PIE is an especially difficult problem because the process itself is self-perpetuating. As air dissects and volume expansion occurs in the interstitial space, blood vessels are compromised and adjacent lung collapses. Macklin postulates that the initial cause of alveolar rupture is not only increased pressure, but also increased shearing force or stretch which occurs in alveoli adjacent to an area of collapse. Therefore, as air collects in the interstitium, causing emphysematous expansion of the involved lung, the adjacent lung collapses due to extrinsic pressure and results in further rupture of alveoli in areas distant to the initial problem. Many reports indicate that congenital pulmonary emphysema and lung cysts are major surgical emergencies in the neonate.5.6 They are usually progressive and compromise pulmonary function early in their course. Rare instances of successful medical management have been reported, T but it is generally agreed that early surgical excision of the involved lobe(s) is mandatory.~, 9 Congenital lesions are usually lobar and spare the rest of the lung, making resection relatively easy and safe. Acquired extra alveolar air, however, is commonly a widespread, bilateral process and radiographs are not always capable of distinguishing if one lobe or the whole lung is involved. The surgical treatment of acqhired extra alveolar air, therefore, is not as universally accepted. Several recent reports have shown that acquired PIE does spontaneously regress, '~ as do pneumatoceles secondary to bacterial pneumonia, in most instances. ~3-'5 The "air block syndrome," as defined by Macklin, '~ includes all forms of extra alveolar air because there is indeed a block of both normal ventilation and circulation. Virtually all manifestations of this syndrome were present in the infants reported here, including tension PIE. All these complications have been successfully treated in the neonate and surgical intervention in this "syndrome" is a rare necessity, except for the placement of thoracostomy tubes. Lung resection for "acquired" air block problems remains a reportable occurrence, tr''9 Cooney et al t9 have recently reported ten infants with severe RDS and PIE, in whom half have required lobectomy. The excised lung had changes such as meta-
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plasia, hyperplasia, hypertrophy, and fibrosis, which are characteristics of bronchopulmonary dysplasia. The three infants reported here, although having varied etiologies for their PIE, required prolonged ventilation with high peak pressures and high inspired oxygen concentrations, all of which predispose to BPD. tlowever, pathologic examinations showed emphysema with marked giant cell reaction and atelectasis, which is more compatible with chronic PIE than with BPD. Selective bronchial intubation with collapse of the involved lung has recently been reported as being successful in halting the progression of PIE '9-2' Once the pressure gradient is relieved, the progression of the lesion should stop. We attempted selective intubation in two of the three infants, with no success; the remaining lung was not capable of providing the minimum pulmonary stability required. 9It remains difficult to decide when medical management has failed and when surgical intervention is necessary. In our patients, continued aggressive medical management may have caused significant delays in the eventual surgical correction of the problem. These infants were exposed to prolonged artificial ventilation and high concentrations of oxygen. Multiple episodes of pneumothorax were associated with periods of hypoxemia. Each infant had many radiographs, tracheal intubations, and drug therapies. Diagnostic procedures such as bronchography and bronchoscopy are not generally recommended as being helpful, and can be hazardous to an infant with compromised respiratory status. 2-~In one infant, attempts at bronchoscopy led to cardiorespiratory arrest and further deterioration of his clinical status. The questions "Can this small, sick infant withstand major pulmonary resection?" and "Ilow much lung must be resected?" are difficult to anticipate. Pneumonectomy has been done successfully in infants, but these reports concern major localized congenital anomalies in which the remaining lung is completely normal? 3 As with selective bronchial intubation, if the contralateral l u n g i s diseased or partially compromised, pneumonectomy may be fatal. The inability to decide in advance the extent of the disease leads to a reluctance to intervene surgically in acquired disease. Fortunately, lobectomy in each of these infants was sufficient; the rapid recovery of all three was in direct contrast to their complicated presurgical course. With the increased survival of the very sick lowbirth-weight infant, this problem will be encguntered more frequently in all neonatal intensive care units. Just as the questions of when to ligate a PDA and when to explore the abdomen in necrotizing enterocolitis remain
The Journal of Pediatrics October 1978
vigorously disputed, clear guidelines for surgical intervention in PIE will also be difficult to establish. Although PIE is being seen and reported with increasing frequency, most cases do spontaneously regress. Once PIE has progressed to the point of large cyst formation and herniation across the midline, however, spontaneous regression is very unlikely. Even after decompression by pneumothorax or collapse by selective bronchial intubation, the PIE recurs and usually progresses when reexpansion occurs. We suggest that in progressive acquired emphysema, the surgical service be consulted early so that resection can be performed as soon as signs indicate that spontaneous regression is unlikely, and when the risks of recurring complications begin to outweigh the risks of surgery. We are grateful to Yolanda Ruiz for the preparation of this manuscript and to Dr. Eduardo Bancalari for his suggestions. REFERENCES I. Murdock AI, Linsao L, Reid MMc C, Sutton MD, Tilak KS, Ulan DA, and Suyer PR: Mechanical ventilation in the respiratory distress syndrome: A controlled trial, Arch Dis Child 45:624, 1970. 2. Gregory GA: Continuous PPB therapy for neonatal respiratory distress, Hosp Practice 7:100, 1972. 3. Emery JL: Interstitial emphysema, pneumothorax, and "air block" in the newborn, Lancet 1:405, 1956. 4. Macklin MT, and Macklin CE: Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: An interpretation of the clinical literature in the light of laboratory experiment, Medicine 23:281, 1944. 5. Sloan II: Lobar obstructive emphysema in infancy treated by lobectomy, J Thorae Surg 26:1, 1953. 6. Pierce WS, de Paredes CG, Raphaely RC, and Waldhausen JA: Pulmonary resection in infants younger than one )'ear of age, J Thorac Cardiovasc Surg 61:875, 1971. 7. Leonidas JC, I/all RT, and Rhodes PG: Conservative management of unilateral pulmonary interstitial emphysema under tension, J PEDIKrR 87:776, 1975. 8. Grossfeld JL, Clatworthy HW Jr, and Fryer TR: Surgical therapy in neonatal air block syndrome, J Thorac Cardiovasc Surg 60:392, 401, 1970. 9. Grossfeld JL, and Ballantyne TV: Surgical respiratory disorders in infancy and childhood, Curt Probl Pediatr 6:3064, 1976. 10. Coffey J: On the natural regression of pulmonary cysts during early infancy, Pediatrics 11:48, 1953. !1. Harris H: Pulmonary pseudocysts in the newborn infant, Pediatrics 59:199, 1977. 12. Lopez JB, Campbell RE, and Boggs TR: Nonoperative resolution of prolonged localized intrapulmonary interstitial emphysema associated with hyaline membrane disease, J PEDIATR91:653, 1977. 13. Potts WJ, and Riker WL: Differentiation of congenital cysts of the lung and those following staphylococcal pneumonia, Arch Surg 61:684, 1950.
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14. Kuhn JP, and Lee SB: Pneumatoceles associated with escherichia coli pneumonia in the newborn, Pediatrics 51:1008, 1973. 15. Papageorgiou A, Bauer CR, Fletcher BD, and Stern L: Klebsiella pneumonia with pneumatocele formation in a newborn infant, Can Med Assoc J 109:1217, 1973. 16. Macklin CC: Transport of air along sheaths of pulmonic blood vessels from alveoli to mediastinum, Arch Intern Med 64:913, 1939. 17. Fletcher BD, Outerbridge EW, YoussefS, and Bolande RP: Pulmonary interstitial emphysema in a newborn infant treated by Iobectomy, PEDIA'rR 54:808, 1974. 18. Magilner AD, Capitanio MA, Wertheimer I, and Burko It: Persistent localized intrapulmonary interstitial emphysema, Radiology 111:379, 1974. 19. Cooney DR, Menke JA, and Allen JE: "Acquired" lobar emphysema: A complication of respiratory distress in premature infants, J Pediatr Surg 12:897, 1977.
20.
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Dickman GL, Short BL, and Krauss DR: Selective bronchial intubation in the management of unilateral pulmonary interstitial emphysema, Am J Dis Child 131:365, 1977. 21. Brooks JG, Bustamante SA, Koops BL, tlelton S, Cooper D, Wesenberg RL, and Simmons MA: Selective bronchial intubation for the treatment of severe localized pulmonary interstitial emphysema in newborn infants, J PEDIA'rR 91:648, 1977. 22. Cohen BE, Passwell J, Jane R, Kalter Y, Cvibab T, and Daleth F: Infantile lobar emphysema, lnt Surg 58:344, 1973. 23. Binet JP, Langlois J, Lesage B, Pottemain M, l-luault G, Saint-Martin J, Conso JF, Miranda R, Patrois R, Cara M, and Rossier A: Pneumonectomie gauche et lobectomie interieure droite, chez un nourrisson porteur de lesions malformatives bulleuses, Presse Med 79:2323, 1971.
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October 1978 The Journal o f P E D I A T R 1 C S
Surgical resection for pulmonary interstitial emphysema in the newborn infant Three patients with pulmonary interstitial emph).sema are presented in whom the course was similar and progressive. Eventually all three infants developed respiratory insu~ciency and chronic dependence on mechanical ventilation, cardiovascular complications of patent ductus arteriosus with congestive heart failure, and seizures probably secondary to intermittent periods of asphyxia and hypoxemia. All infants underwent Iobectomy and recovered rapidly. Follow-up examinations have shown some residual puhnonary abnormalities. A 11three infants are progressing within the normal range for motor development.
Charles R. Bauer, M.D.,* M. Jayne Brennan, P.N.P., Coleen Doyle, D.P.N.P., and Catherine A. Poole, M.D., M i a m i , Fla.
WITH THE ADVENT of sophisticated respiratory therapies adaptable to the very small, immature infant, the mortality from pulmonary insufficiency has been markedly reduced, but morbidity has increased as a result of complications o f these therapies. The "air block" syndrome (pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema, and even pneumoperitoneum) is beconling a common event in neonatal intensive care nurseries). 2 Three patients are presented in whom PIE occurred. The first followed a course consistent with an intrauterine ~,iral pneumonia, the second had a severe respiratory distress syndrome, and the third had massive aspiration of formula. All three infants required intubation and mechanical ventilation, ~Jeveloped PIE, and followed a progressive downhill course, with similar cardiovascular and neurologie complications. Because of respiratory dependence and worsening clinical findings, all three infants underwent pulmonary resection. The three infants survived the surgery, were eventually discharged, and have been followed for 10 to 13 months.
Front the Departments of Pediatrics and Radiolog); University of Miami School of Medicine. *Reprint address: Universityof Miami School of Medicine, Department of Pediatrics, P.O. Box 320875, 31iami, FL 33152.
Vol. 93, No. 4, pp. 656-661
CASE R E P O R T S Patient 1. This male infant was born at Jackson Memorial Hospital to a white, 24-year-old gravida 1 by emergency cesarean section because of a prolapsed cord. The pregnancy had been uncomplicated until eight days prior to delivery, when the membranes ruptured spontaneously. Abbreviations used BPD: bronchopulmonary dysplasia (N)CDAP: (nasal) continuous distending airway pressure CHF: congestive heart failure PDA: patent ductus arteriosus PIE: pulmonary interstitial emphysema RDS: respiratory distress syndrome The infant weighed 1,300 gm and was small for his estimated gestation, which by Dubowitz examination was 34 weeks. The Apgar score was 9 at i and at 5 minutes. On admission, the infant was in moderate respiratory distress and was treated with oxygen and nasal continuous distending airway "pressure. The initial chest radiograph demonstrated diffuse granularity and air trapping. The ifffant was treated with penicillin and gentamicin because of the prolonged rupture of membranes. His condition deteriorated rapidly over the first day, requiring intubation and mechanical ventilation. A pneumomediastinum developed and soon progressed to a pneumopericardium and left-sided pneumothorax, requiring drainage by thoracostomy. Seizures were observed on the second day ~/nd were treaied with phenobarbital. A right-sided tension pneumothorax developed on the third day, requiring drainage.
0022-3476/78/100656+06500.60/0 9 1978 The C. V. Mosby Co.
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Fig. 1.A, With re-expansion ofboth lungs follov,'ing the insertion ofthoracostomy tubes, numerous variably sized cystic collections of interstitial air were seen in the left upper lobe. The large rounded accumulation ofair superimposed on the cardiac silhouette was !oculated in the posterior mediastinum. I B, Progressive enlargement of the interstitial collections occurred, with collapse of the left lower lobe, mediastinal shift to the right, and severe compromise of the right lung. The right mainstem bronchus was selectively intubated, in an unsuccessful attempt tO decompress the left lung and re-expand the right lung. C, A follow-up examination of the chest at one year of age (10 t& months corrected)revealed residual chroni6 pulmonary changes on the fight side. The left lower lobe was well expanded and relatively clear. The heart was slightly enlarged, with elevation of the apex suggesting right ventricular hypertrophy.
Fig. 2.A, Diffuse pulmonary disease was present bilaterally. The right lower lobe was overexpanded, secondary to multiple variably sized cystic collections of interstitial air. B, Progressive enlargement of the cystic interstitial emphysema occurred, with severe mediastinal shift to the left, compromise of the entire left lung, and total atelectasis of 9the right middle and upper lobeS. C, Following surgical resectioh of the right lower lobe, the right middle and upper lobes re-expanded, and the mediastinal st/uctures returned to the midline. At 12 months of age (corrected), there were minimal chronic interstitial and pleural changes withslight overexpansion of the chest. The diagnosis of PIE in the left lung was first made after the tension was relieved and the lung re-expanded (Fig. I, A). After the chest tubes were removed, the PIE persisted with the formation of many large confluent cystic areas. 9 The fight mainstem bronchus was intubated for two days in an unsuccessful attempt to collapse the emphysematous left lung (Fig. 1, B). After the endotracheal tube was repositioned above the carina, a tension pneumothorax on the left recurred, again requiring the placement of a chest tube. The infant could not be weaned from - the respirator. On the eighteenth day of life, because the interstitial air and cysts were still present and the infant was dependent on a respirator, a left upper lobectomy was perfoz'med and ";vas tolerated very ,.,.'ell. Pathologic examination of the left upper lobe revealed an immature lung with chronic cystic interstitial emphysema and secondar~ patchy pulmonary collapse. Some interstitial fibrosis and marked giant cell reaction were also_ present.
Over the next two weeks, the infant was weaned slowly from the respirator. A patent ductus artefiosus and congestive heart failure briefly complicated the recovery, but were controlled by administration of digitalis and restriction of fluids. Another major complication was aphrenic nerve paralysis on the side of the surgery, which resulted in recurrent pulmonary atelectasis. The infant gradually improved over the next two months and was discharged on the seventy ninth day of life. The infant was seen in the follow-up clinic at corrected ages of 3, 6, and 10tAmonths, lie is developmentally within normal limits for both the Bayley and Denver Developmental tests, tie has had no major pulmonary problems and has tolerated mild Upper respiratory infections very well. Chest radiographs (Fig. 1, C) remain abnormal, but have shown sign!ficant improvement over the last year, with restoradan_ of diaphragmatic function. Patient 2. This male infant was born at an outlying hospital to a black, 21-year-old gravida 1 by a normal 7,'aginal delivery. The
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The Journal o f Pediatrics October 1978
Fig. 3.A, Diffuse bilateral pneumonia was secondary to aspiration. Within the left lung there were several cystic collections of interstitial emphysema. B, Progressive overexpansion of the left lung led to anterior herniation and mediastinal shift to the right. The right lung was compromised, but there had been partial resolution of the aspiration pneumonia. C, At 10 months of age, residual chronic pulmonary changes were present, though the left upper lobe and the entire fight lung were normally expanded.
pregnancy was uncomplicated until nine days prior to delivery, when the membranes ruptured spontaneously. The infant weighed 1,200 gm and was estimated by Dubowitz examination to be 30 weeks of gestation. The Apgar score was 2 at I and at 5 minutes. The infant '.vas intubated and given oxygen for approximately 5 minutes before spontaneous respirations were established. Because of continued respiratory distress, he ,,,,'as transferred to the Neonatal Intensive Care Unit at Jackson Memorial Hospital at age 4 hours. On admission, the infant was being ventilated with up to 95% inspired oxygen. The first chest radiograph showed diffuse haziness and was read as compatible with RDS. The infant was treated with penicillin and gentamicin because of the prolonged rupture of membranes, tle initially improved, but on the fourth day had generalized seizures followed by cardiorespiratory arrest. Bilateral pneumothoraees were demonstrated at this time, and were drained by thoracostomy tubes. A chest radiograph demonsrated bilateral PIE, pneumomediastinum, extra pleural air over the diaphragm, and a massive pneumoperitoneum. The chest tubes were removed within the next 48 hours, but the PIE pe~isted (Fig. 2, A). The process ofweaning from oxygen and the ventilator was complicated by the appearance o f a PDA and signs of CHF. The PIE persisted over the next two weeks, with carbon dioxide retention becoming a recurrent problem. By approximately one month of age, the infant was dependent on a respirator. His CttF was kept under control but he could not be adequately nourished because of restriction of fluid intake. The PIE had progressed to form large confluent cysts in the right lower lobe, which caused a marked mediastinal shift, collapse of the fight upper and middle lobes, and severe compromise of the left lung (Fig. 2, B). A fight lower lobectomy was performed on day 35 of age. Pathologic examination of the right lower lobe revealed severe interstitial emphysema with giant cell reaction and focal atelectasis. The infant did very '.,,'ell postoperaiively, and was weaned from the respirator within one week of surgery, tie was discharged on the eighty seventh day of life. The infant has been seen at corrected ages of 3, 6, and 12
months. Developmentally, he is within normal limits on the Denver and Bayley Developmental scales. His chest radiographs continue to show minimal interstitial changes (Fig. 2, C). He has been hospitalized once at age 9 months for an acute episode of wheezing, and wheezing has been a chronic problem. Patient 3. This male infant, the first of twins, was born to a black 20-year-old pfimigravida by normal vaginal delivery. The pregnancy had been uncomplicated until the day prior to admission, when the membranes ruptured spontaneously. The mother developed a fever of I01.6~ at which time blood cultures were done and antibiotic therapy was started at the local hospital, and she was transferred to Jackson Memorial tlospital for delivery. At delivery, the infant weighed, 1,110 gm and was estimated by Dubowitz examination to be approximately 30 weeks of gestation. Apgar scores were 2 and 6 at I and 5 minutes, respectively. The infant was intubated and given oxygen during transfer to the Neonatal Intensive Care Nursery. tte was treated with penicillin and gentamicin because of the prolonged rupture of membranes and maternal fever. The infant's initial chest radiograph was read as normal. Ite was quickly weaned to 25% inspired oxygen, but CDAP alone was unsuccessful because of persistent apnea. Aminophylline therapy controlled the apnea and the infant was then removed from the respirator and the CDAP. tie was transferred to Mr. Sinai Medical Center, a regional secondary care center, on the seventeenth day of life, weighing 1,240 gm and doing well. After approximately two weeks at Mr. Sinai Hospital, he had an episode of aspiration of formula and required intubation and mechanical ventilation. Ite was returned to the Neonatal Intensive Care Unit at Jackson Memorial Hospital, where the admis- . sion che.;t radiograph showed a pneumomediastinum and massive aspiration pneumonia. The infant had recurrent seizures, which were treated with phenobarbital. Mechanical ventilation at high peak pressures and high oxygen concentrations was required for a prolonged period of time. During the acute stage, a PDA ,,~ith CtlF occurred. This was treated medically by diuretics, digoxin, and restriction of fluids.
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By the fifth day after the aspiration, bilateral cystic changes compatible with PIE were seen on chest radiographs (Fig. 3, A). Respiratory distress and CHF were persistent. The trachea was extubated approximately two weeks after the aspiration but progressive emphysema of the left lung resulted in herniation across the mediastinum and secondary atelectasis of the right lung (Fig. 3, B). At 389 weeks postaspiration, his PDA and CHF were persistent and he had continued respiratory distress evidenced by retractions, wheezing, and poor feeding. At 4~Aweeks postaspiration (53 days of life), surgical intervention was considered, lndomethacin was used in an attempt to close the PDA but failed, and medical management was not successful in controlling the heart failure. The infant required reintubation. Intermittent episodes of seizure activity were treated with phenobarbital. While on the respirator, an attempt was made to selectively occlude the left bronchus and allow the compressed right lung to re-expand. Some re-expansion of the right lung occurred, but the left lung failed to decompress. The infant rapidly developed bradycardia and hypoxia. Two additional attempts to collapse the emphysematous left lung were similarly unsuccessful, with rapid clinical deterioration. The infant was examined by bronchoscopy at age 60 days and no intrinsic or extrinsic bronchial obstruction was seen. The PDA persisted, as did occasional seizures. At 78 days, a lung scan demonstrated markedly decreased perfusion to both the right lung, which was mostly collapsed, and to the large, emphysematous left lung. Severe apnea and bradycardia became more frequent. On day 95 of age, a left lower lobectomy and ligation of the PDA were performed. The left lower lobe was diffusely emphysematous, with minimal patchy focal atelectasis on pathologic examination. Postoperatively, the radiologic findings were improved but the mediastinal shift and PIE persisted in spite of the fact that the resected left lower lobe had been the most severely affected. He did well clinically and the trachea was extubated on the second postoperative day. tte subsequently developed a purulent pleural effusion which responded to systemic antibiotic therapy, but because of acute carbon dioxide retention, he again required mechanical ventilation. Seizures recurred with no evidence of meningitis. By one week postoperatively, day 103 of life, the infant no longer required ventilator), support and was feeding well. He was discharged on the one hundred thirtieth day of life (thirty fourth day postoperative). The infant was seen at corrected ages of 3, 6, 9, and 13 months. He is within the normal range in his developmental progress, llis respiratory status remains borderline. He has wheezing, rales and retractions, and some upper airway obstruction. He has had two upper respiratory infections but recovered without incident. His chest radiograph remains abnormal (Fig. 3, C). DISCUSSION Extra alveolar air, which is recognized as a major cau.se of mortality in the neonate,~ can seriously interfere with normal cardiovascular and/or pulmonary function. Large collections of air in the interstitial spaces can splint the lung, making normal respiration imposs!b!e. As air
Surgical resection for puhnonar), interstitial emph)'sema
659
dissects along perivascular channels, blood vessels are compressed and pulmonary circulation is compromised. Macklin and Macklin ~ experimentally demonstrated the pathology of air escape in animals. They showed that pulmonary interstitial emphysema, pneumomediastinum, pneumothorax, pneumopericardium, subcutaneous emphysema, and pneumoperitoneum are all a part of a continumum of dissecting air, initiated by rupture of alveoli. This dissection process is not relieved until the cause of the increased pressure in the alveoli is relieved. PIE is an especially difficult problem because the process itself is self-perpetuating. As air dissects and volume expansion occurs in the interstitial space, blood vessels are compromised and adjacent lung collapses. Macklin postulates that the initial cause of alveolar rupture is not only increased pressure, but also increased shearing force or stretch which occurs in alveoli adjacent to an area of collapse. Therefore, as air collects in the interstitium, causing emphysematous expansion of the involved lung, the adjacent lung collapses due to extrinsic pressure and results in further rupture of alveoli in areas distant to the initial problem. Many reports indicate that congenital pulmonary emphysema and lung cysts are major surgical emergencies in the neonate.5.6 They are usually progressive and compromise pulmonary function early in their course. Rare instances of successful medical management have been reported, T but it is generally agreed that early surgical excision of the involved lobe(s) is mandatory.~, 9 Congenital lesions are usually lobar and spare the rest of the lung, making resection relatively easy and safe. Acquired extra alveolar air, however, is commonly a widespread, bilateral process and radiographs are not always capable of distinguishing if one lobe or the whole lung is involved. The surgical treatment of acqhired extra alveolar air, therefore, is not as universally accepted. Several recent reports have shown that acquired PIE does spontaneously regress, '~ as do pneumatoceles secondary to bacterial pneumonia, in most instances. ~3-'5 The "air block syndrome," as defined by Macklin, '~ includes all forms of extra alveolar air because there is indeed a block of both normal ventilation and circulation. Virtually all manifestations of this syndrome were present in the infants reported here, including tension PIE. All these complications have been successfully treated in the neonate and surgical intervention in this "syndrome" is a rare necessity, except for the placement of thoracostomy tubes. Lung resection for "acquired" air block problems remains a reportable occurrence, tr''9 Cooney et al t9 have recently reported ten infants with severe RDS and PIE, in whom half have required lobectomy. The excised lung had changes such as meta-
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Batter et aL
plasia, hyperplasia, hypertrophy, and fibrosis, which are characteristics of bronchopulmonary dysplasia. The three infants reported here, although having varied etiologies for their PIE, required prolonged ventilation with high peak pressures and high inspired oxygen concentrations, all of which predispose to BPD. tlowever, pathologic examinations showed emphysema with marked giant cell reaction and atelectasis, which is more compatible with chronic PIE than with BPD. Selective bronchial intubation with collapse of the involved lung has recently been reported as being successful in halting the progression of PIE '9-2' Once the pressure gradient is relieved, the progression of the lesion should stop. We attempted selective intubation in two of the three infants, with no success; the remaining lung was not capable of providing the minimum pulmonary stability required. 9It remains difficult to decide when medical management has failed and when surgical intervention is necessary. In our patients, continued aggressive medical management may have caused significant delays in the eventual surgical correction of the problem. These infants were exposed to prolonged artificial ventilation and high concentrations of oxygen. Multiple episodes of pneumothorax were associated with periods of hypoxemia. Each infant had many radiographs, tracheal intubations, and drug therapies. Diagnostic procedures such as bronchography and bronchoscopy are not generally recommended as being helpful, and can be hazardous to an infant with compromised respiratory status. 2-~In one infant, attempts at bronchoscopy led to cardiorespiratory arrest and further deterioration of his clinical status. The questions "Can this small, sick infant withstand major pulmonary resection?" and "Ilow much lung must be resected?" are difficult to anticipate. Pneumonectomy has been done successfully in infants, but these reports concern major localized congenital anomalies in which the remaining lung is completely normal? 3 As with selective bronchial intubation, if the contralateral l u n g i s diseased or partially compromised, pneumonectomy may be fatal. The inability to decide in advance the extent of the disease leads to a reluctance to intervene surgically in acquired disease. Fortunately, lobectomy in each of these infants was sufficient; the rapid recovery of all three was in direct contrast to their complicated presurgical course. With the increased survival of the very sick lowbirth-weight infant, this problem will be encguntered more frequently in all neonatal intensive care units. Just as the questions of when to ligate a PDA and when to explore the abdomen in necrotizing enterocolitis remain
The Journal of Pediatrics October 1978
vigorously disputed, clear guidelines for surgical intervention in PIE will also be difficult to establish. Although PIE is being seen and reported with increasing frequency, most cases do spontaneously regress. Once PIE has progressed to the point of large cyst formation and herniation across the midline, however, spontaneous regression is very unlikely. Even after decompression by pneumothorax or collapse by selective bronchial intubation, the PIE recurs and usually progresses when reexpansion occurs. We suggest that in progressive acquired emphysema, the surgical service be consulted early so that resection can be performed as soon as signs indicate that spontaneous regression is unlikely, and when the risks of recurring complications begin to outweigh the risks of surgery. We are grateful to Yolanda Ruiz for the preparation of this manuscript and to Dr. Eduardo Bancalari for his suggestions. REFERENCES I. Murdock AI, Linsao L, Reid MMc C, Sutton MD, Tilak KS, Ulan DA, and Suyer PR: Mechanical ventilation in the respiratory distress syndrome: A controlled trial, Arch Dis Child 45:624, 1970. 2. Gregory GA: Continuous PPB therapy for neonatal respiratory distress, Hosp Practice 7:100, 1972. 3. Emery JL: Interstitial emphysema, pneumothorax, and "air block" in the newborn, Lancet 1:405, 1956. 4. Macklin MT, and Macklin CE: Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: An interpretation of the clinical literature in the light of laboratory experiment, Medicine 23:281, 1944. 5. Sloan II: Lobar obstructive emphysema in infancy treated by lobectomy, J Thorae Surg 26:1, 1953. 6. Pierce WS, de Paredes CG, Raphaely RC, and Waldhausen JA: Pulmonary resection in infants younger than one )'ear of age, J Thorac Cardiovasc Surg 61:875, 1971. 7. Leonidas JC, I/all RT, and Rhodes PG: Conservative management of unilateral pulmonary interstitial emphysema under tension, J PEDIKrR 87:776, 1975. 8. Grossfeld JL, Clatworthy HW Jr, and Fryer TR: Surgical therapy in neonatal air block syndrome, J Thorac Cardiovasc Surg 60:392, 401, 1970. 9. Grossfeld JL, and Ballantyne TV: Surgical respiratory disorders in infancy and childhood, Curt Probl Pediatr 6:3064, 1976. 10. Coffey J: On the natural regression of pulmonary cysts during early infancy, Pediatrics 11:48, 1953. !1. Harris H: Pulmonary pseudocysts in the newborn infant, Pediatrics 59:199, 1977. 12. Lopez JB, Campbell RE, and Boggs TR: Nonoperative resolution of prolonged localized intrapulmonary interstitial emphysema associated with hyaline membrane disease, J PEDIATR91:653, 1977. 13. Potts WJ, and Riker WL: Differentiation of congenital cysts of the lung and those following staphylococcal pneumonia, Arch Surg 61:684, 1950.
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Surgical resection for pulmonary interstitial emplo.sema
14. Kuhn JP, and Lee SB: Pneumatoceles associated with escherichia coli pneumonia in the newborn, Pediatrics 51:1008, 1973. 15. Papageorgiou A, Bauer CR, Fletcher BD, and Stern L: Klebsiella pneumonia with pneumatocele formation in a newborn infant, Can Med Assoc J 109:1217, 1973. 16. Macklin CC: Transport of air along sheaths of pulmonic blood vessels from alveoli to mediastinum, Arch Intern Med 64:913, 1939. 17. Fletcher BD, Outerbridge EW, YoussefS, and Bolande RP: Pulmonary interstitial emphysema in a newborn infant treated by Iobectomy, PEDIA'rR 54:808, 1974. 18. Magilner AD, Capitanio MA, Wertheimer I, and Burko It: Persistent localized intrapulmonary interstitial emphysema, Radiology 111:379, 1974. 19. Cooney DR, Menke JA, and Allen JE: "Acquired" lobar emphysema: A complication of respiratory distress in premature infants, J Pediatr Surg 12:897, 1977.
20.
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Dickman GL, Short BL, and Krauss DR: Selective bronchial intubation in the management of unilateral pulmonary interstitial emphysema, Am J Dis Child 131:365, 1977. 21. Brooks JG, Bustamante SA, Koops BL, tlelton S, Cooper D, Wesenberg RL, and Simmons MA: Selective bronchial intubation for the treatment of severe localized pulmonary interstitial emphysema in newborn infants, J PEDIA'rR 91:648, 1977. 22. Cohen BE, Passwell J, Jane R, Kalter Y, Cvibab T, and Daleth F: Infantile lobar emphysema, lnt Surg 58:344, 1973. 23. Binet JP, Langlois J, Lesage B, Pottemain M, l-luault G, Saint-Martin J, Conso JF, Miranda R, Patrois R, Cara M, and Rossier A: Pneumonectomie gauche et lobectomie interieure droite, chez un nourrisson porteur de lesions malformatives bulleuses, Presse Med 79:2323, 1971.
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