Pierre Robin syndrome and pulmonary hypertension

Pierre Robin Syndrome and Pulmonary Hypertension By E,H. Dykes, P.A.M. Raine, D.S. Arthur, I.K. Drainer, and D.G. Young Glasgow, Scotland 9 Five infants with Pierre Robin syndrome developed evidence of carbon dioxide retention and congestive cardiac failure despite measures to alleviate upper airway obstruction. Investigations included chest radiography, electrocardiography, echocardiography, and cardiac catheterization; pulmonary hypertension was diagnosed. In two cases raised main pulmonary artery pressures of 40 mm Hg and 120 mm Hg were recorded. Relief of upper airway obstruction was achieved by tracheostomy in three cases and nasopharyngeal intubation in two cases, with reversal of signs of cor pulmonale in each. Four patients progressed well with no recurrence of cardiac problems but one died suddenly one month after apparently successful management by tracheostomy. INDEX WORDS: Pierre Robin syndrome; pulmonary hypertension.

H E P I E R R E Robin syndrome (PRS), or Robin anomalad, consists of micrognathia, glossoptosis, and respiratory obstruction usually associated with cleft palate (CP). The imprecision of this definition and the range of severity of the syndrome lead to wide variations in estimates of incidence, from 1 : 2,000 to 1 : 50,000 live births. One in 8,500 live births was probably an accurate assessment of the incidence of PRS with CP in one particular study ~ as strict criteria for diagnosis were applied; however, up to 40% of cases of PRS do not have CP. In this syndrome, mortality rates of 20% to 30% are common, 14 though 10% has been reported in a large series. 5 Despite a gradual decline in mortality, the condition continues to pose grave risks and demands early, active, and concerted management. At the Royal Hospital for Sick Children, Yorkhill, Glasgow, 59 cases (29 males, 30 females) of moderate or severe PRS have been recognized during the past 27 years. A previous report of 25 cases occurring in the period 1957 to 1964 included 5 deaths. 6 Between 1965 and 1977, 23 cases resulted in 4 deaths. In 1977, the problem of pulmonary hypertension and cor pulmonale was encountered in association with PRS, and in the period 1978 to 1984 a further 4 such associations arose in 10 PRS cases. The presentation, diagnosis, management, and o u t -

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Journal of Pediatric Surgery, Vo120, No 1 (February), 1985: pp 49-52

come of these 5 cases forms the basis of this report. MATERIALS AND METHODS Five babies (4 male, 1 female) presented immediately or shortly after birth with marked degrees of respiratory difficulty due to PRS; four had CP. Details of birth weights, gestation, and associated anomalies appear in Table 1. Each patient subsequently developed raised capillary pCO2 and clinical evidence of cor pulmonale and pulmonary hypertension, confirmed by chest radiography and electrocardiography. Maximum pCO2 (mm Hg) and cardiothoracic ratio (C/T ratio) are shown in Table 2. The case histories follow.

Case 1 A female infant presented at birth with respiratory obstruction, severe micrognathia (Fig 1), and paresis of the soft palate with anteversion of the muscular tissue beneath the posterior edge of the hard palate. Oropharyngea] airway, ventral suspension, and prone nursing maintained an adequate airway and feeding was by nasogastric tube. At three weeks, a degree of cardiac enlargement on chest radiography (Fig 2) and right ventricular hypertrophy with right axis deviation on electrocardiography was noted. Weight was gained slowly with tube feeding but intermittent episodes of aspiration and chest infection occurred. At five months, clinical evidence of congestive cardiac failure and cor pulmonale developed with gross cardiomegaly (Fig 3), hepatomegaly, triple cardiac rhythm, and cyanosis, together with pulmonary crepitations and rapidly rising capillary pCO 2. Endotracheal intubation could not be achieved on account of the grossly abnormal mandible and restricted jaw joint movement, and tracheostomy was necessary to secure the airway. Diuretics, digitalization, and intermittent positive pressure ventilation reversed cardiac failure and pCO2 gradually returned to normal. Cardiac catheterization and angiography excluded a cardiac malformation but confirmed pulmonary hypertension (main pulmonary artery pressure 40 mm Hg). Subsequent progress was good with resolution of evidence of cot pulmonale and no difficulty after removal of the

From the Departments of Paediatric Surgery and Anaesthesia, Royal Hospital for Sick Children, Yorkhill, Glasgow. Presented in Liverpool at the 31st Annual International Congress of the British Association of Paediatric Surgeons, July 25-27, 1984. Address reprint requests to P.A.M. Raine, Department of Paediatric Surgery, Royal Hospital for Sick Children, Yorkhill, Glasgow, G3 8S J, Scotland. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2001-0012503.00/0 49

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DYKES ET AL

Table 1. Birth Weights, Gestation, and Associated Anomalies of PRS Cases Birth Weight (kg)

Gestation (wks)

Associated Anomalies

1 (F.R.)

2.7

40

KlippeI-Fiel

2 (W.L.) 3 (F.B.) 4 (P.F.)

3.6 1.9 3.4

40 37 40

Ureterocele --Kneist Syndrome

5 (J.B.)

2.4

38

V.S.D.

Case

tracheostomy tube at age two; neurological development is normal. Mandibular growth has been disappointing and, at age six, the child awaits surgery for temporomandibular joint ankylosis.

Fig 1. Case 1 - - L a t e r a l head and n e c k radiograph showing severe micrognathia and restricted pharyngeal airway.

Case 2 A male infant with PRS required prone nursing and nasogastric feeding from birth. At ten weeks the infant was referred to R.H.S.C, Yorkhill with persistent upper airway obstruction with episodes of pulmonary aspiration and failure to gain weight. At 15 weeks evidence of hepatomegaly and peripheral and pulmonary edema suggested congestive cardiac failure. Echocardiography revealed right ventricular hypertrophy and excluded a major cardiac malformation. Endotracheal intubation and intermittent positive pressure ventilation with diuretics and digitalis therapy reversed the cardiac failure. However, persistent left lower lobe collapse was investigated by tracheobronchography, which showed narrowing and elongation of the left main bronchus probably due to compression by an enlarged pulmonary artery. Hypercapnia and clinical evidence of pulmonary hypertension recurred when continuous positive airway pressure was removed and cardiac catheterization, while confirming normal cardiac and great vessel anatomy, recorded a main pulmonary artery pressure of systemic systolic levels (120 mm Hg). To alleviate any residual upper airway obstruction, tracheostomy was performed at five months and was followed by slow resolution of signs of pulmonary hypertension. As progress was good, the tracheostomy was removed at eight months but signs of pulmonary hypertension recurred at 18 months and it was reestablished. Following CP repair and second removal of tracheostomy at age four, progress has been uneventful and neurological development is normal.

Case 3 A male second twin with PRS had some evidence of suprasternal and intercostal recession despite nursing in ventral suspension from birth. During the first four weeks, capillary pCO2 slowly rose and evidence of mild pulmonary hypertension appeared. Echocardiography excluded congenital heart disease. A more rapid rise in pCO~ with signs of incipient cardiac failure lead to initial attempts at endotracheal intubation which proved extremely difficult; tracheostomy was therefore performed at 35 days. Thereafter cardiac size reverted to normal and the infant thrived on nasogastric feeding. One month later the infant was found dead in his cot without evidence of asphyxiation or aspiration. Autopsy revealed no other congenital abnormality or clear cause of death; postmortem culture of blood from the heart, of pharyngeal secretions, and of the nasogastric tube grew Klebsiella organisms and raised the possibility of an acute cardiorespiratory arrest secondary to septicemia, although there was no supporting antemortem clinical evidence.

Table 2. Maximum pCO 2 and Maximum Cardiothoracic Ratio of PRS Cases

1 2 3 4 5

Case

Maximum pCO2 (mms Hg)

Maximum C/T ratio (%)

(F.R.) (W.L.) (F.B.) (P.F.) (J.B.)

122 112 105 66 59

75 68 58 72 65

Fig 2. Case 1 - - C h e s t radiograph showing slight cardiomagaly at age 3 weeks.

PIERRE ROBIN AND PULMONARY HYPERTENSION

Fig 3. Case 1--Chest radiograph showing gross cardiomogaly and pulmonary edema at age 5 months.

Case 4 A male infant with features of the Robin anomolad together with metaphyseal dysplasia was found to have the Kneist syndrome. Early respiratory and feeding difficulties required careful prone nursing and nasogastric feeding. A mild increase in capillary pCO2 and evidence of cor pulmonale gradually developed and at two months a nasopharyngeal tube was inserted in addition to a nasogastric tube. The respiratory distress was relieved with slow resolution of cardiomegaly. At four months the nasopharyngeal tube was removed and subsequent progress was good with no further respiratory obstruction.

Case 5

A male infant with PRS was noted to have severeglossoptosis at birth with the tongue displaced into the horse-shoe CP, causing respiratory difficulty. Prone nursing did not completely abolish sternal recession and upper airway obstruction, and at one week a nasopharyngeal tube was inserted. A systoliccardiac murmur characteristic of ventricular septal defect was heard and this was confirmed on echocardiography. A slight increase in pCO2 persisted and was associated with evidence of mild pulmonary artery hypertension. A lip/tongue adhesion was performed and although this partly dehisced, a more anterior position of the tongue tip was maintained. Gradual weight gain and return to normal pCO2allowed removalof the nasopharyngeal tube at four weeks with good progress thereafter. DISCUSSION

Pulmonary hypertension has resulted from upper airway obstruction due to enlarged tonsils and adenoids, 7 Crouzon's disease, s subglottic stenosis, 9 achondroplasia, 1~sleep, ~l laryngotracheomalacia, t2 and facio-auriculo-vertebral sequence. 13 The literature contains a number of single case reports of pulmonary hypertension secondary to PRS, ~4-~8but the association is not widely recorded. Evidence of acquired pulmo-

51

nary hypertension was present in two patients with PRS in a review of 32 deaths in patients with facial clefts; 19 21 had significant congenital cardiac lesions although the incidence of congenital heart disease in a prospective review of 150 facial cleft patients was only 1.3%. 19 Pulmonary hypertension in these circumstances is probably caused by alveolar hypoventilation leading to hypoxia, which is a trigger for pulmonary vascular constriction in sensitive individualsJ 5'~8'2~The mechanism is possibly potentiated by hypercapnia, acidosis, and reflex responses. Pulmonary hypertension results and cor pulmonale and congestive cardiac failure gradually develop. Pulmonary edema cannot be explained by this pathogenesis but may be related to hypoxia and vigorous respiratory efforts producing high negative intrathoracic pressure. ~5'2~ Pulmonary edema was present in cases 1 and 2 and rapidly responded to adequate oxygenation and positive airway pressure. The relief of upper airway obstruction from an early stage is the key to prevention of the dangerous sequence leading to cor pulmonale. Many means of achieving this have been tried with differing enthusiasm and success and each has its strong advocates. Assiduous prone nursing 22 or ventral suspension 6 and carefully supervised oral or tube feeding may be sufficient. The tongue may be prevented from obstructing the pharynx by use of a cleft obturator, 5'23 lip/tongue anastomosis, 3'2425 or Kirschner wire fixation. 26 Nasopharyngeal intubation ~8'27 can provide adequate relief of airway obstruction and a nasooesophageal tube 28 has produced benefit by interrupting build-up of high negative pharyngeal pressure. Tracheostomy has been performed in cases of PRS complicated by pulmonary hypertension with satisfactory reversal of changes 14'16'17 and has been used routinely in some series to alleviate upper airway obstruction. 2'23 In this series, cases 1 and 2 presented with fulminating congestive cardiac failure from cor pulmonale, and intermittent positive pressure ventilation with maintenance of a completely unrestricted airway were essential; tracheostomy was considered mandatory. In case 3, the gradual development of pulmonary hypertension was recognized and endotracheal intubation was elected but proved exceedingly difficult and hazardous.

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A s t h e g o o d results w i t h n a s o p h a r y n g e a l i n t u b a tion 27 h a d not t h e n b e e n r e p o r t e d , t r a c h e o s t o m y was p e r f o r m e d . In cases 4 a n d 5, n a s o p h a r y n g e a l intubation reversed early evidence of pulmonary hypertension satisfactorily; lip/tongue anastomosis p r o b a b l y did not c o n t r i b u t e to this in c a s e 5. O u r p r e f e r e n c e n o w w o u l d be for e a r l y nasop h a r y n g e a l i n t u b a t i o n w i t h r e s o r t to t r a c h e o s t o m y o n l y if d e t e r i o r a t i o n o c c u r r e d . B e f o r e 1977, n i n e d e a t h s h a d o c c u r r e d in 48 P R S cases in this c e n t e r in 20 years. T h e m o r t a l ity r a t e o f 19% c o m p a r e s closely w i t h o t h e r series. 1'2'4 T h e m a j o r i t y o f d e a t h s w e r e d u e to serious a s s o c i a t e d c a r d i a c lesions ~9 b u t episodes o f a s p h y x i a t i o n a n d a s p i r a t i o n w e r e identified. O n e case, h o w e v e r h a d f e a t u r e s o f c o n g e s t i v e

c a r d i a c f a i l u r e and, in r e t r o s p e c t , m a y h a v e developed pulmonary hypertension although the diagnosis was not m a d e . It s e e m s likely t h a t , prior to t h e first r e p o r t in 1969,14 u n r e c o g n i z e d p u l m o n a r y h y p e r t e n s i o n h a d been r e s p o n s i b l e for d e a t h s in P R S . W e c o n s i d e r t h a t c a r e f u l assessm e n t a n d i n v e s t i g a t i o n of t h e possibility o f pulm o n a r y h y p e r t e n s i o n in all P R S cases is w a r r a n t e d a n d t h a t its e a r l y a n d e n e r g e t i c t r e a t m e n t is a d v i s a b l e . ACKNOWLEDGMENT

We wish to thank the Consultant Neonatologists and Paediatricians for expeditious referral of cases, the Cardiac Investigation Unit for expertise in establishing the diagnoses, and Miss June Lawson for typing the manuscript.

REFERENCES

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