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Respiratory distress and neck mass in a neonate
CLINI CAL- PATH O LOGI CAL C O N F E R E N C E * Jay Bernstein. Editor
R e s p i r a t o r y distress a n d n e c k m a s s in a n e o n a t e
David F. Hardwick, M.D., F.R.C.P.(C),** Edward J. Cormode, M.D., F.R.C.P.(C), and David G. Riddell, M.D., F.R.C.P.(C), Vancouver, B.C., Canada
THIS MALE INFANT was born to a para 1, gravida 2, blood type O-Rh negative nidther at term. A previous pregnancy had terminated with the birth of a normal infant at term. This pregnancy had been entirely normal. There was no evidence of isoimmunization. At approximately 40 weeks of gestation there was a spontaneous rupture of the membranes, followed by delivery in seven hours. During the final two hours of labor the fetal heart rate varied from 135 to 165 beats per minute. After a second stage of 10 minutes, the infant was born spontaneously from a left occipito-anterior position. The Apgar scores were 5 at one minute and 6 at four minutes, respectively. Because of inadequate respiratory effort the infant was immediately intubated and given oxygen by positive pressure. He was then extubated at four minutes and transferred to the nursery, where,-during the next four hours, he became cyanosed several times and required ventilatory assistance by bag and mask. The infant was then transferred at five hours of age to the Vancouver General Hospital Intensive Care Nursery. He was intu.bated immediately upon arrival and given ventilatory assistance. Physical examination revealed a gray cyanotic male infant, who weighed 3,270 gin, measured 49 cm in crownheel length, and had a head circumference of 35 cm. The fontanelles and scalp were normal. The eyes were normal with bilateral red reflexes. Mouth and palate were normal. A large, soft, semimobile mass was located in the lower anterior neck. There was no lymphadenopathy. Respirations were 60 per minute, with a shallow and From the Division o f Pediatric Pathology, Department of Pathology, The University o f British Columbia, Vancouver General Hospital, and Children's Hospital *Sponsored by the Pediatric Pathology Club. **Reprint address: Department of Pathology, The University of British Columbia, 2075 Wesbrook Place, Vancouver, B.C. V6T IW5.
gasping pattern, chest retractions, and with very poor air entry bilaterally. The heart rate was a regular 120 beats per minute, and the heart sounds were normal. No murmurs were heard. The abdomen was soft, and the liver edge and spleen tip were just palpable. The kidneys and genitals were normal. There were no abnormalities of skin or extremities. The infant was semiconscious and had a poor Moro reflex and a poor grasp response. Abbreviations used CSF: cerebrospinal fluid HMD: hyaline membrane disease PBI: protein bound iodine Results of investigations done at this time were as follows: Hemoglobin concentration of 16.5 gm/dl; white blood cells 17,300/ram ~ with 26% polymorphonuclears, 7% immature, 3% eosinophils, 4% basophils, 55% lymphocytes, 5% monocytes; blood glucose concentration 40 rag/ dl; values of blood gases (capillary) following intubation were pH 7.25, Pr 19 mm Hg, base deficit 17, actual bicarbonate 11 mEq/1; Urinalysis: specific gravity 1.014, protein 4 + , glucose negative, occasional white blood cells, and many granular and hyaline casts; serum concentration of calcium 8.4 mg/dl; PBI 11/xg/dl; VDRL negative, A roentgenogram of the chest showed the endotracheal tube to be high in the trachea and both lungs well expanded, with slight displacement of the trachea to the right; heart size was normal. The infant was ventilated via a nasotracheal tube and respirator with 40% oxygen, rate 50 per minute, and pressure 25 cm water. He was given an infusion of 10% dextrose in water and 10 mEq of sodium bicarbonate. Color improved and his condition remained stable for the next eight hours. An additional 10 mEq sodium bicarbonate was administered. At the age of 12 hours he had a tonic convulsion that lasted two minutes. The cerebroThe Journal of P E D I A T R I C S Vol. 89, No. 3, pp. 501-505
501
502
Hardwick, Cormode, and Riddell
s p i n a l fluid was x a n t h o c h r o m i c a n d slightly cloudy, with 8,400 r e d b l o o d c e l l s / m m 3 a n d 100 w h i t e b l o o d c e l l s / m m ~ w i t h a differential o f 47% p o l y m o r p h o n u c l e a r cells a n d 53% l y m p h o c y t e s . C o n c e n t r a t i o n o f C S F glucose was 24 mg/dl
a n d p r o t e i n 500 m g / d l . T h e i n f a n t was given
ampicillin and kanamycin. Convulsions and cyanotic p e r i o d s c o n t i n u e d i n t e r m i t t e n t l y . A t age 16 h o u r s h e h a d a c a r d i a c arrest following a c o n v u l s i o n , B l o o d gas values were p H 7.13, Pco~ 18 m m Hg, base deficit 22, actual b i c a r b o n a t e 6.0 m E q / 1 . F o u r e p i s o d e s o/" c a r d i a c arrest o c c u r r e d d u r i n g the n e x t five hours. H e r e c e i v e d 20 m E q o f N a H C O 3 . D e a t h o c c u r r e d at 21 hours. DISCUSSION DR. CORMODE.* A brief resume of the protocol shows that we are dealing with a full-term newborn infant who was asphyxiated at birth. Following the initial resuscitation, the infant remained in poor condition for four hours. He was transferred, in shock, to the Intensive Care Nursery, where he was immediately reintubated. The important physical findings included the brief but very abnormal neurologic examination, the midline mass in the lower neck, and the respiratory distress, which may have been a reflection of shock, airway obstruction, or lung disease. The infant's course was complicated at the age of 12 hours by convulsions, which continued thereafter, and at 16 hours by the first of five cardiac arrests. He died at 21 hours of age. In my discussion I plan to identify the clinical problems, to discuss each problem individually, and then to tie them together to explain his death. Problem 1: Rh-negative mother. This was the mother's second pregnancy. We are told that there was no serologic evidence of isoimmunization. The infant was delivered at term, and there was no enlargement of the liver or spleen. Hemoglobin concentration was 16.5 gm/dl. Therefore, I do not think that Rh-sensitization played a role in the infant's difficulties. Problem 2: Perinatal asphyxia. The only sign of fetal distress was the irregularity of the fetal heart rate for the two hours before delivery. Apgar scores of 5 at one minute and 6 at four minutes, respectively, are evidence of intrauterine asphyxia. The causes of antenatal asphyxia are many. They include maternal factors, such as compression of aorta and inferior vena cava when the mother lies in supine position, tetanic uterine contractions, 9 hypotension secondary to anaesthesia with hyperventilation, and toxemia; placental factors, such as premature separation and abruption; and fetal causes, such as occlusion or compression of the umbilical cord and fetal hypotension secondary to drugs that cross the placenta. We are not given any clues that suggest an etiology for this infant's antenatal asphyxia. Problem 3: Respiratory distress. This infant would seem to have had two patterns of respiratory distress. The infant did not appear initially to be making appropriate respiratory efforts, an observation confirmed in part by the low Apgar scores. There are many explanations for the problem, but the most common *Department of Pediatrics, The University of British Columbia.
The Journal of Pediatrics September 1976
perhaps is depression of the central nervous system. Depression may be secondary to asphyxia, which he had, to analgesic or enaegthetic agents administered to mother, or to trauma from misapplied forceps or precipitate delivery. The other pattern of respiratory distress with tachypnea, gasping, indrawing, and poor air entry would indicate disease within the respiratory tract. The most common cause of this at birth would be hyaline membrane disease in the premature infant. As we are told, he was born at term and the measurements of growth seem to confirm this. I do not feel, therefore, that H M D is a contributing factor. Choanal atresia has been ruled out by the passage of a nasotracheal tube. Laryngomalacia, laryngeal webs, and vocal cord paralysis should all have been diagnosed at the time of laryngoscopy for intubation. Also the fact that the child continued to have some respiratory distress while intubated would suggest to me that these were not present. Obstruction from external masses is a factor and will be discussed under Problem 4. Other possible causes of respiratory distress in this infant include aspiration of amniotic fluid, intrauterine pneumonia, diaphragmatic hernia, pneumothorax, and congenital heart disease. The normal chest roentgenogram makes these possibilities unlikely. There was no evidence clinically of heart failure. I feel that of the causes listed above the intrauterine asphyxia is the most likely cause of this infant's respiratory difficulties, compounded by Problem 4, a neck mass. Problem 4: Neck mass. We are told the infant had a large mass, which was soft and semimobile in the lower anterior neck. We are not told if the infant had stridor when the tube was not in place. The only investigation reported to determine the origin of the mass was a PBI of 11 #g/dl. The normal range at birth is reported to be 7 to 10 ~g/dl and at one week 7 to 12 ~g/dl. I am willing, therefore, to accept this value as normal. It would have been helpful to have had a lateral roentgenogram of the neck to see if this mass were compressing the trachea and to see if the mass contained any calcifications that might suggest a teratoma o f the thyroid gland. The mass was in the midline, which would militate against a cystic hygroma or branchial cyst, both occurring more laterally. It could be a hemangioma, but I think that the mass is most likely related to the thyroid gland. It may be a thyroglossal cyst, an ectopie thyroid, or a goiter. We are given no history o f maternal ingestion of goitrogens or of a low- or high-iodine intake. We are given no family history of goiters. The protocol does not suggest the infant was a cretin, and the fontanelle was reported to be normal; cretins commonly have a large fontanelle. H0rthle cell tumors, adenocarcinomas, and teratomas have all been described in this age group, but are exceedingly rare. Infants born to mothers with thyrotoxicosis may also develop goiters on the basis of placental transfer o f long-acting thyroid stimulation; however, our maternal history rules this out. In summary, I feel that the mass in the neck is of thyroid origin, most likely a benign thyroid goiter, and that it was causing extrinsic compression of the trachea, further aggravating the asphyxia and acidosis, which this infant had been subjected to in utero and which was never properly corrected.
Volume 89 Number 3
Problem 5: Urine abnormalities. The urine is reported as having specific gravity of 1.014, protein content of 4 + , and many granular casts. The fact that the infant was excreting urine at all is encouraging in view of potential renal damage from prolonged hypoxemia and hypotension. It would be of further importance to know the exact volumes of urine excreted. I feel this infant had sufficient asphyxia and hypotension to account for impaired renal perfusion. Problem 6: Metabolic acidosis. The first laboratory evidence of acidosis was noted after the intubation at 4 hours of age. He had a pH 7.25, a Pco~ 19 m m Hg, a base deficit of 17, and an actual bicarbonate of 11 mEq/1. The low Pco~ suggests that he was initially easily ventilated, which is against an obstructive component to the respiratory distress. The large base deficit and low actual bicarbonate suggest a metabolic origin for the acidosis. At no time are we given values o f Po~. In view of the repeated mention of cyarrosis, however, I assume he was severely hypoxic. 1 therefore feel that the most likely cause of his acidosis is a lactic acidosis secondary to hypoxia and that we need not consider the various organic acidemias. Problem 7: Convulsions. Convulsions were first noted at 12 hours of age. Blood glucose and calcium concentrations were normal on admission. Examination of cerebrospinal fluid showed 8,400 red blood cells and 100 white blood cells/mm 3. Bacteriologic studies are not available. Concentrfitions of cerebrospinal fluid glucose and protein were 25 mg/dl and 500 mg/dl, respectively. In bloody lumbar punctures, the results can be difficult to interpret. There are more white blood cells than one would expect to see on the basis of the peripheral white blood cell count. The differential is normal, however, and the glucose concentration is within normal limits. The protein concentration is elevated. We are not told if the specimen was centrifuged in an attempt to differentiate an old form a recent hemorrhage. The history does not suggest prolonged rupture of membranes, prolonged labor, or foul amniotic fluid. Any of these might suggest an intrauterine infection with meningitis. The history does, however, confirm severe asphyxia. I feel that the convulsions were secondary to the asphyxia. In view of the blood in the cerebrospinal fluid, however, there is a possibility of intracerebral bleeding as the origin of the convulsions. I would like at this point, to consider the bicarbonate therapy that the infa m was given. Finberg warned in 1967 of the dangers of infusion of hyperosmolar solutions such as sodium bicarbonate. A number of potentially deleterious effects, such as renal damage and intracranial hemorrhage, may occur following the infusion of hypertonic solutions. The precise danger point will vary with the state of the patient, the concentration of the hyperosmolar solution, the nature of the solute, and the rate of administration. Maximum safe tolerance for a normally hydrated subject would be in the order of an increase of 24 mosmol/kg water over 4 hours. Three milliequivalents per kilogram of body weight of sodium bicarbonate, given intravenously, will raise the osmolality by 7.5 mosmol/kg of body water. Therefore, three such, infusions over a four-hour period will reach the probable tolerance level of a healthy animal. The sequence of events after a sudden, large rise in osmolality will be: (1) expansion of
Respiratory distress and neck mass
5 03
vascular volume, (2) shrinking of cells, (3) reduction in volume and pressure of the CSF, (4) capillary dilatation and possible cerebral hemorrhage, and (5) shift of hydrogen ions out of desiccated ceils producing acidemia. With the expansion of extracellular fuids there is a dilution of extracellular buffers and a release of protons from intracellular buffers such as hemoglobin. This infant received 20 mEq of sodium bicarbonate over a seven- to eight-hour period from the time of admission to the Intensive Care Nursery until the first cardiac arrest. This would be at the upper limit of safety proposed by Finberg. We are told that 20 mEq of bicarbonate were infused over the last few hours of life. i f he did not already have a cerebral hemorrhage, this could very well cause one. In summary, I feel that intrauterine asphyxia caused his initial respiratory depression. He was inadequately resuscitated at birth and went on to suffer continued hypoxia because of airway obstruction secondary to extrinsic compression by the neck mass, probably a goiter. Convulsions and renal abnormalities were secondary to asphyxia. At age 15 hours he had a cardiac arrest. Attempts to resuscitate, following the arrest, resulted in an overdose of sodium bicarbonate, with the possibility of a subsequent cerebral hemorrhage.
Final clinical diagnosis Intrauterine asphyxia Thyroid trachea
goiter
causing
mechanical
obstruction
of
Severe h y p o x i a with irreversible m e t a b o l i c acidosis Cerebral hemorrhage AUTOPSY DR. D. F. HARt~WmK.* The infant was normally developed (weight 3,270 gm), except for the obvious swelling in his neck. The thyroid gland was markedly enlarged, weight 18.5 gm (normal 2.4 gm), and was adherent to the trachea, encroaching upon its lumen inferior to the cricoid cartilage. The lungs weighed 59 gm combined (normal 57 gm) and appeared atelectatic and granular on cut section. There was no gross evidence of pulmonary interstitial emphysema. The pleural spaces were free of air. The cardiovascular system was normal. All other organs appeared grossly normal and were of normal weight. In particular, the liver and spleen were normal. Examination of the central nervous system showed a small (5 ml), left-sided, subdural hematoma and a modest, diffuse, subarachnoid hemorrhage. Sectioning showed 10 ml of blood in the ventricles, with hemorrhage in the area of the right vena terminalis, thus confirming Dr. Cormode's suspicion. Microscopically, the thyroid gland was hyperplastic with small acini and very ~ttle colloid. There was no evidence of inflammation. Thyroid tissue could be seen penetrating and extending welt into the tracheal lumen (Fig. 1). Bruising of the lumenal aspect of the intratracheat thyroid was severe. The lungs were congested, and hyaline membranes were noted in all lung fields. Subpleural and inter*Professor and Head, Pediatric Pathology, The University of British Columbia.
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The Journal of Pediatrics September 1976
O Fig. 1. Intratracheal thyroid. Note the intratracheal location of the thyroid tissue (arrows). The lumen of the trachea is markedly reduced, stitial perivascular air spaces, representing pulmonary interstitial emphysema, were noted. The liver and spleen were n o r m a l showing only normal amounts of extramedullary hematopoiesis and no stainable iron. The kidneys were substantially immature, having many glomeruli still being formed at the capsular surface. Despite the abnormal urinary findings, the remaining histologic picture was normal. All pre- and postmortem cultures of blood and CSF were negative. The unusual feature of this case is the goiter. Benign thyroid goiters in infants unassociated with hyper- or hypothyroidism are unusual. Iodine, antithyroid medication, and goitrogens ingested by pregnant women have all on occasion produced goiters in newborn infants. Most of these infants are hypothyroid. Discussion of intratracheal location of goiters comes mostly from the European literature. It is not known whether thyroid tissue becomes entrapped within the developing trachea or whether it actually invades into the trachea. The tissue may be found anywhere within the trachea, but usually is around the posterolateral aspect of the larynx. In over two-thirds of cases there is a goitrous enlargement of the normally placed thyroid tissueF -~ Dr. Cormode has captured the basic themes of this case. Some amplification of his comments seems to be in order. The cause of the intrauterine asphyxia was unknown, and there were no significant clinical signs of impending trouble. The early respiratory distress was further complicated by the effects of repeated intubation on an already partially obstructed trachea. We often see edema, ulceration, and inflammation secondary to prolonged intubation. The presence of hyaline membranes in this 16-hourold infant may represent H M D or oxygen administration plus ventilation. It is worthwhile noting that there was a dramatic increment in pressure required to ventilate this child shortly before he died. This is almost certainly due to the presence of pulmonary interstitial emphysema.
We concur with Dr. Cormode's assessment of the dangers of osmotic overload and the potential danger of subependymal plate hemorrhage as occurred in this patient. The infant received 70 mEq of bicarbonate over his short lifetime. Simmons and associates ~ in a retrospective study correlated intracranial hemorrhage with hypernatremia due to excessive bicarbonate administration. Another etiology for subependymal plate hemorrhages proposed by Cole and associates ~' suggests that impeded venous return from the head from whatever cause produces a transudation of fluid and finally blood across the terminal veins.
Final pathological diagnosis
Intratracheal thyroid goiter Respiratory distress syndrome (hyaline disease) Intracranial hemorrhages Pulmonary interstitial emphysema
membrane
REFERENCES
1. Finberg L: Dangers to infants caused by changes in osmolal concentration, Pediatrics 40:1031, 1967. 2. Schaffer AJ, and Avery ME: Diseases of the newborn, ed 3, Philadelphia, 1971, WB Saunders Company, p 449. 3. Smith JD, and Cager CR: Simple goiter in infancy and childhood, J Okla State Med Assoc 59:622, 1966. 4. Bongiovanni AM, Eberlein WR, Thomas PZ, and Anderson WB: Sporadic goiter in the newborn, J Clin Endocrinol Metab 16:146, 1956. 5. Carswelt F, Kerr MM, and Hutchison JH: Congenital goiter and hypothyroidism produced by maternal ingestion of iodides, Lancet 1:1241, 1970. 6. Hassan AI, Aref GH, and Kassen AS: Congenital iodide-
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induced goiter with hypothyroidism, Arch Dis Child 43:702, 1968. 7. Randolph J, Grunt JA, and Vawter GF: Medical and surgical aspects of intratracheal goiter, N Engl J Med 268:457, 1963. 8. Simmons MA, Adcock EW, Bard H, and Battaglia FC:
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Hypernatremia and intracranial hemorrhage in neonates, N Engl J Med 291:6, 1974. 9. Cole VA, Durbin GM, Olaffson A, Reynolds EOR, Rivers RPA, and Smith JF: Pathogenesis of intraventricular hemorrhage in newborn infants, Arch Dis Child 49:722, 1974.
R e s p i r a t o r y distress a n d n e c k m a s s in a n e o n a t e
David F. Hardwick, M.D., F.R.C.P.(C),** Edward J. Cormode, M.D., F.R.C.P.(C), and David G. Riddell, M.D., F.R.C.P.(C), Vancouver, B.C., Canada
THIS MALE INFANT was born to a para 1, gravida 2, blood type O-Rh negative nidther at term. A previous pregnancy had terminated with the birth of a normal infant at term. This pregnancy had been entirely normal. There was no evidence of isoimmunization. At approximately 40 weeks of gestation there was a spontaneous rupture of the membranes, followed by delivery in seven hours. During the final two hours of labor the fetal heart rate varied from 135 to 165 beats per minute. After a second stage of 10 minutes, the infant was born spontaneously from a left occipito-anterior position. The Apgar scores were 5 at one minute and 6 at four minutes, respectively. Because of inadequate respiratory effort the infant was immediately intubated and given oxygen by positive pressure. He was then extubated at four minutes and transferred to the nursery, where,-during the next four hours, he became cyanosed several times and required ventilatory assistance by bag and mask. The infant was then transferred at five hours of age to the Vancouver General Hospital Intensive Care Nursery. He was intu.bated immediately upon arrival and given ventilatory assistance. Physical examination revealed a gray cyanotic male infant, who weighed 3,270 gin, measured 49 cm in crownheel length, and had a head circumference of 35 cm. The fontanelles and scalp were normal. The eyes were normal with bilateral red reflexes. Mouth and palate were normal. A large, soft, semimobile mass was located in the lower anterior neck. There was no lymphadenopathy. Respirations were 60 per minute, with a shallow and From the Division o f Pediatric Pathology, Department of Pathology, The University o f British Columbia, Vancouver General Hospital, and Children's Hospital *Sponsored by the Pediatric Pathology Club. **Reprint address: Department of Pathology, The University of British Columbia, 2075 Wesbrook Place, Vancouver, B.C. V6T IW5.
gasping pattern, chest retractions, and with very poor air entry bilaterally. The heart rate was a regular 120 beats per minute, and the heart sounds were normal. No murmurs were heard. The abdomen was soft, and the liver edge and spleen tip were just palpable. The kidneys and genitals were normal. There were no abnormalities of skin or extremities. The infant was semiconscious and had a poor Moro reflex and a poor grasp response. Abbreviations used CSF: cerebrospinal fluid HMD: hyaline membrane disease PBI: protein bound iodine Results of investigations done at this time were as follows: Hemoglobin concentration of 16.5 gm/dl; white blood cells 17,300/ram ~ with 26% polymorphonuclears, 7% immature, 3% eosinophils, 4% basophils, 55% lymphocytes, 5% monocytes; blood glucose concentration 40 rag/ dl; values of blood gases (capillary) following intubation were pH 7.25, Pr 19 mm Hg, base deficit 17, actual bicarbonate 11 mEq/1; Urinalysis: specific gravity 1.014, protein 4 + , glucose negative, occasional white blood cells, and many granular and hyaline casts; serum concentration of calcium 8.4 mg/dl; PBI 11/xg/dl; VDRL negative, A roentgenogram of the chest showed the endotracheal tube to be high in the trachea and both lungs well expanded, with slight displacement of the trachea to the right; heart size was normal. The infant was ventilated via a nasotracheal tube and respirator with 40% oxygen, rate 50 per minute, and pressure 25 cm water. He was given an infusion of 10% dextrose in water and 10 mEq of sodium bicarbonate. Color improved and his condition remained stable for the next eight hours. An additional 10 mEq sodium bicarbonate was administered. At the age of 12 hours he had a tonic convulsion that lasted two minutes. The cerebroThe Journal of P E D I A T R I C S Vol. 89, No. 3, pp. 501-505
501
502
Hardwick, Cormode, and Riddell
s p i n a l fluid was x a n t h o c h r o m i c a n d slightly cloudy, with 8,400 r e d b l o o d c e l l s / m m 3 a n d 100 w h i t e b l o o d c e l l s / m m ~ w i t h a differential o f 47% p o l y m o r p h o n u c l e a r cells a n d 53% l y m p h o c y t e s . C o n c e n t r a t i o n o f C S F glucose was 24 mg/dl
a n d p r o t e i n 500 m g / d l . T h e i n f a n t was given
ampicillin and kanamycin. Convulsions and cyanotic p e r i o d s c o n t i n u e d i n t e r m i t t e n t l y . A t age 16 h o u r s h e h a d a c a r d i a c arrest following a c o n v u l s i o n , B l o o d gas values were p H 7.13, Pco~ 18 m m Hg, base deficit 22, actual b i c a r b o n a t e 6.0 m E q / 1 . F o u r e p i s o d e s o/" c a r d i a c arrest o c c u r r e d d u r i n g the n e x t five hours. H e r e c e i v e d 20 m E q o f N a H C O 3 . D e a t h o c c u r r e d at 21 hours. DISCUSSION DR. CORMODE.* A brief resume of the protocol shows that we are dealing with a full-term newborn infant who was asphyxiated at birth. Following the initial resuscitation, the infant remained in poor condition for four hours. He was transferred, in shock, to the Intensive Care Nursery, where he was immediately reintubated. The important physical findings included the brief but very abnormal neurologic examination, the midline mass in the lower neck, and the respiratory distress, which may have been a reflection of shock, airway obstruction, or lung disease. The infant's course was complicated at the age of 12 hours by convulsions, which continued thereafter, and at 16 hours by the first of five cardiac arrests. He died at 21 hours of age. In my discussion I plan to identify the clinical problems, to discuss each problem individually, and then to tie them together to explain his death. Problem 1: Rh-negative mother. This was the mother's second pregnancy. We are told that there was no serologic evidence of isoimmunization. The infant was delivered at term, and there was no enlargement of the liver or spleen. Hemoglobin concentration was 16.5 gm/dl. Therefore, I do not think that Rh-sensitization played a role in the infant's difficulties. Problem 2: Perinatal asphyxia. The only sign of fetal distress was the irregularity of the fetal heart rate for the two hours before delivery. Apgar scores of 5 at one minute and 6 at four minutes, respectively, are evidence of intrauterine asphyxia. The causes of antenatal asphyxia are many. They include maternal factors, such as compression of aorta and inferior vena cava when the mother lies in supine position, tetanic uterine contractions, 9 hypotension secondary to anaesthesia with hyperventilation, and toxemia; placental factors, such as premature separation and abruption; and fetal causes, such as occlusion or compression of the umbilical cord and fetal hypotension secondary to drugs that cross the placenta. We are not given any clues that suggest an etiology for this infant's antenatal asphyxia. Problem 3: Respiratory distress. This infant would seem to have had two patterns of respiratory distress. The infant did not appear initially to be making appropriate respiratory efforts, an observation confirmed in part by the low Apgar scores. There are many explanations for the problem, but the most common *Department of Pediatrics, The University of British Columbia.
The Journal of Pediatrics September 1976
perhaps is depression of the central nervous system. Depression may be secondary to asphyxia, which he had, to analgesic or enaegthetic agents administered to mother, or to trauma from misapplied forceps or precipitate delivery. The other pattern of respiratory distress with tachypnea, gasping, indrawing, and poor air entry would indicate disease within the respiratory tract. The most common cause of this at birth would be hyaline membrane disease in the premature infant. As we are told, he was born at term and the measurements of growth seem to confirm this. I do not feel, therefore, that H M D is a contributing factor. Choanal atresia has been ruled out by the passage of a nasotracheal tube. Laryngomalacia, laryngeal webs, and vocal cord paralysis should all have been diagnosed at the time of laryngoscopy for intubation. Also the fact that the child continued to have some respiratory distress while intubated would suggest to me that these were not present. Obstruction from external masses is a factor and will be discussed under Problem 4. Other possible causes of respiratory distress in this infant include aspiration of amniotic fluid, intrauterine pneumonia, diaphragmatic hernia, pneumothorax, and congenital heart disease. The normal chest roentgenogram makes these possibilities unlikely. There was no evidence clinically of heart failure. I feel that of the causes listed above the intrauterine asphyxia is the most likely cause of this infant's respiratory difficulties, compounded by Problem 4, a neck mass. Problem 4: Neck mass. We are told the infant had a large mass, which was soft and semimobile in the lower anterior neck. We are not told if the infant had stridor when the tube was not in place. The only investigation reported to determine the origin of the mass was a PBI of 11 #g/dl. The normal range at birth is reported to be 7 to 10 ~g/dl and at one week 7 to 12 ~g/dl. I am willing, therefore, to accept this value as normal. It would have been helpful to have had a lateral roentgenogram of the neck to see if this mass were compressing the trachea and to see if the mass contained any calcifications that might suggest a teratoma o f the thyroid gland. The mass was in the midline, which would militate against a cystic hygroma or branchial cyst, both occurring more laterally. It could be a hemangioma, but I think that the mass is most likely related to the thyroid gland. It may be a thyroglossal cyst, an ectopie thyroid, or a goiter. We are given no history o f maternal ingestion of goitrogens or of a low- or high-iodine intake. We are given no family history of goiters. The protocol does not suggest the infant was a cretin, and the fontanelle was reported to be normal; cretins commonly have a large fontanelle. H0rthle cell tumors, adenocarcinomas, and teratomas have all been described in this age group, but are exceedingly rare. Infants born to mothers with thyrotoxicosis may also develop goiters on the basis of placental transfer o f long-acting thyroid stimulation; however, our maternal history rules this out. In summary, I feel that the mass in the neck is of thyroid origin, most likely a benign thyroid goiter, and that it was causing extrinsic compression of the trachea, further aggravating the asphyxia and acidosis, which this infant had been subjected to in utero and which was never properly corrected.
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Problem 5: Urine abnormalities. The urine is reported as having specific gravity of 1.014, protein content of 4 + , and many granular casts. The fact that the infant was excreting urine at all is encouraging in view of potential renal damage from prolonged hypoxemia and hypotension. It would be of further importance to know the exact volumes of urine excreted. I feel this infant had sufficient asphyxia and hypotension to account for impaired renal perfusion. Problem 6: Metabolic acidosis. The first laboratory evidence of acidosis was noted after the intubation at 4 hours of age. He had a pH 7.25, a Pco~ 19 m m Hg, a base deficit of 17, and an actual bicarbonate of 11 mEq/1. The low Pco~ suggests that he was initially easily ventilated, which is against an obstructive component to the respiratory distress. The large base deficit and low actual bicarbonate suggest a metabolic origin for the acidosis. At no time are we given values o f Po~. In view of the repeated mention of cyarrosis, however, I assume he was severely hypoxic. 1 therefore feel that the most likely cause of his acidosis is a lactic acidosis secondary to hypoxia and that we need not consider the various organic acidemias. Problem 7: Convulsions. Convulsions were first noted at 12 hours of age. Blood glucose and calcium concentrations were normal on admission. Examination of cerebrospinal fluid showed 8,400 red blood cells and 100 white blood cells/mm 3. Bacteriologic studies are not available. Concentrfitions of cerebrospinal fluid glucose and protein were 25 mg/dl and 500 mg/dl, respectively. In bloody lumbar punctures, the results can be difficult to interpret. There are more white blood cells than one would expect to see on the basis of the peripheral white blood cell count. The differential is normal, however, and the glucose concentration is within normal limits. The protein concentration is elevated. We are not told if the specimen was centrifuged in an attempt to differentiate an old form a recent hemorrhage. The history does not suggest prolonged rupture of membranes, prolonged labor, or foul amniotic fluid. Any of these might suggest an intrauterine infection with meningitis. The history does, however, confirm severe asphyxia. I feel that the convulsions were secondary to the asphyxia. In view of the blood in the cerebrospinal fluid, however, there is a possibility of intracerebral bleeding as the origin of the convulsions. I would like at this point, to consider the bicarbonate therapy that the infa m was given. Finberg warned in 1967 of the dangers of infusion of hyperosmolar solutions such as sodium bicarbonate. A number of potentially deleterious effects, such as renal damage and intracranial hemorrhage, may occur following the infusion of hypertonic solutions. The precise danger point will vary with the state of the patient, the concentration of the hyperosmolar solution, the nature of the solute, and the rate of administration. Maximum safe tolerance for a normally hydrated subject would be in the order of an increase of 24 mosmol/kg water over 4 hours. Three milliequivalents per kilogram of body weight of sodium bicarbonate, given intravenously, will raise the osmolality by 7.5 mosmol/kg of body water. Therefore, three such, infusions over a four-hour period will reach the probable tolerance level of a healthy animal. The sequence of events after a sudden, large rise in osmolality will be: (1) expansion of
Respiratory distress and neck mass
5 03
vascular volume, (2) shrinking of cells, (3) reduction in volume and pressure of the CSF, (4) capillary dilatation and possible cerebral hemorrhage, and (5) shift of hydrogen ions out of desiccated ceils producing acidemia. With the expansion of extracellular fuids there is a dilution of extracellular buffers and a release of protons from intracellular buffers such as hemoglobin. This infant received 20 mEq of sodium bicarbonate over a seven- to eight-hour period from the time of admission to the Intensive Care Nursery until the first cardiac arrest. This would be at the upper limit of safety proposed by Finberg. We are told that 20 mEq of bicarbonate were infused over the last few hours of life. i f he did not already have a cerebral hemorrhage, this could very well cause one. In summary, I feel that intrauterine asphyxia caused his initial respiratory depression. He was inadequately resuscitated at birth and went on to suffer continued hypoxia because of airway obstruction secondary to extrinsic compression by the neck mass, probably a goiter. Convulsions and renal abnormalities were secondary to asphyxia. At age 15 hours he had a cardiac arrest. Attempts to resuscitate, following the arrest, resulted in an overdose of sodium bicarbonate, with the possibility of a subsequent cerebral hemorrhage.
Final clinical diagnosis Intrauterine asphyxia Thyroid trachea
goiter
causing
mechanical
obstruction
of
Severe h y p o x i a with irreversible m e t a b o l i c acidosis Cerebral hemorrhage AUTOPSY DR. D. F. HARt~WmK.* The infant was normally developed (weight 3,270 gm), except for the obvious swelling in his neck. The thyroid gland was markedly enlarged, weight 18.5 gm (normal 2.4 gm), and was adherent to the trachea, encroaching upon its lumen inferior to the cricoid cartilage. The lungs weighed 59 gm combined (normal 57 gm) and appeared atelectatic and granular on cut section. There was no gross evidence of pulmonary interstitial emphysema. The pleural spaces were free of air. The cardiovascular system was normal. All other organs appeared grossly normal and were of normal weight. In particular, the liver and spleen were normal. Examination of the central nervous system showed a small (5 ml), left-sided, subdural hematoma and a modest, diffuse, subarachnoid hemorrhage. Sectioning showed 10 ml of blood in the ventricles, with hemorrhage in the area of the right vena terminalis, thus confirming Dr. Cormode's suspicion. Microscopically, the thyroid gland was hyperplastic with small acini and very ~ttle colloid. There was no evidence of inflammation. Thyroid tissue could be seen penetrating and extending welt into the tracheal lumen (Fig. 1). Bruising of the lumenal aspect of the intratracheat thyroid was severe. The lungs were congested, and hyaline membranes were noted in all lung fields. Subpleural and inter*Professor and Head, Pediatric Pathology, The University of British Columbia.
504
Hardwick, Cormode, and Riddell
The Journal of Pediatrics September 1976
O Fig. 1. Intratracheal thyroid. Note the intratracheal location of the thyroid tissue (arrows). The lumen of the trachea is markedly reduced, stitial perivascular air spaces, representing pulmonary interstitial emphysema, were noted. The liver and spleen were n o r m a l showing only normal amounts of extramedullary hematopoiesis and no stainable iron. The kidneys were substantially immature, having many glomeruli still being formed at the capsular surface. Despite the abnormal urinary findings, the remaining histologic picture was normal. All pre- and postmortem cultures of blood and CSF were negative. The unusual feature of this case is the goiter. Benign thyroid goiters in infants unassociated with hyper- or hypothyroidism are unusual. Iodine, antithyroid medication, and goitrogens ingested by pregnant women have all on occasion produced goiters in newborn infants. Most of these infants are hypothyroid. Discussion of intratracheal location of goiters comes mostly from the European literature. It is not known whether thyroid tissue becomes entrapped within the developing trachea or whether it actually invades into the trachea. The tissue may be found anywhere within the trachea, but usually is around the posterolateral aspect of the larynx. In over two-thirds of cases there is a goitrous enlargement of the normally placed thyroid tissueF -~ Dr. Cormode has captured the basic themes of this case. Some amplification of his comments seems to be in order. The cause of the intrauterine asphyxia was unknown, and there were no significant clinical signs of impending trouble. The early respiratory distress was further complicated by the effects of repeated intubation on an already partially obstructed trachea. We often see edema, ulceration, and inflammation secondary to prolonged intubation. The presence of hyaline membranes in this 16-hourold infant may represent H M D or oxygen administration plus ventilation. It is worthwhile noting that there was a dramatic increment in pressure required to ventilate this child shortly before he died. This is almost certainly due to the presence of pulmonary interstitial emphysema.
We concur with Dr. Cormode's assessment of the dangers of osmotic overload and the potential danger of subependymal plate hemorrhage as occurred in this patient. The infant received 70 mEq of bicarbonate over his short lifetime. Simmons and associates ~ in a retrospective study correlated intracranial hemorrhage with hypernatremia due to excessive bicarbonate administration. Another etiology for subependymal plate hemorrhages proposed by Cole and associates ~' suggests that impeded venous return from the head from whatever cause produces a transudation of fluid and finally blood across the terminal veins.
Final pathological diagnosis
Intratracheal thyroid goiter Respiratory distress syndrome (hyaline disease) Intracranial hemorrhages Pulmonary interstitial emphysema
membrane
REFERENCES
1. Finberg L: Dangers to infants caused by changes in osmolal concentration, Pediatrics 40:1031, 1967. 2. Schaffer AJ, and Avery ME: Diseases of the newborn, ed 3, Philadelphia, 1971, WB Saunders Company, p 449. 3. Smith JD, and Cager CR: Simple goiter in infancy and childhood, J Okla State Med Assoc 59:622, 1966. 4. Bongiovanni AM, Eberlein WR, Thomas PZ, and Anderson WB: Sporadic goiter in the newborn, J Clin Endocrinol Metab 16:146, 1956. 5. Carswelt F, Kerr MM, and Hutchison JH: Congenital goiter and hypothyroidism produced by maternal ingestion of iodides, Lancet 1:1241, 1970. 6. Hassan AI, Aref GH, and Kassen AS: Congenital iodide-
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induced goiter with hypothyroidism, Arch Dis Child 43:702, 1968. 7. Randolph J, Grunt JA, and Vawter GF: Medical and surgical aspects of intratracheal goiter, N Engl J Med 268:457, 1963. 8. Simmons MA, Adcock EW, Bard H, and Battaglia FC:
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Hypernatremia and intracranial hemorrhage in neonates, N Engl J Med 291:6, 1974. 9. Cole VA, Durbin GM, Olaffson A, Reynolds EOR, Rivers RPA, and Smith JF: Pathogenesis of intraventricular hemorrhage in newborn infants, Arch Dis Child 49:722, 1974.