Arch. Dis. Childh., 1967, 42, 659.

Transient Respiratory Distress Syndrome in the Newborn *

The variable duration and severity of the the infant had been breathing 100/o 02 by mask at respiratory distress syndrome (RDS) make it 10 I./min. for 15 minutes, the initial arterial sample was difficult to assess any therapeutic regime. We have obtained. Subsequently, if the infant's condition observed 12 infants who at age 4 hours had clinical permitted, arterial Po2 was measured, with the breathing room air for 15 minutes. Blood was and biochemical findings indicative of moderate to infant analysed for pH and carbon dioxide tension (Paco.,) by severe respiratory distress syndrome but who the interpolation method (Astrup, J0rgensen, Siggaard improved rapidly with a standard therapeutic Andersen, and Engel, 1960) and the base deficit (negative regime, their respiratory distress disappearing or base excess) calculated from a nomogram (Siggaard becoming minimal during the first day of life. We Andersen, 1962). The base deficit values were corrected describe the clinical, acid-base, and blood-gas for oxygen saturation and the effect of increases in course of these infants. For comparison, we also PaCo2 (Dell, Engel, and Winters, 1966). The arterial studied a group of 19 distressed premature newborns oxygen tension (Pao2) was determined with a modified who initially manifested a similar clinical and bio- Clark electrode (Radiometer-Beckman) calibrated with water and maintained at 38 C. All chemical picture, but in whom the respiratory tonometred readings were corrected for temperature differences and distress syndrome persisted beyond age 30 hours Pao2 for non-linearity of the electrode at oxygen tensions despite the same therapeutic regime. For the above 200 mm. Hg. Minimum colonic temperature purposes of comparison, we refer to those infants at the time of the initial sample was 36 0 C. Arterial with minimal or no respiratory distress at age 18 pH values were converted to hydrogen ion concentration hours as the transient respiratory distress syndrome for averaging and the mean values reconverted to pH group (TRD), and those whose respiratory distress for presentation. The 12 infants in the TRD group had initial clinical persisted beyond age 30 hours as the moderate-severe infants respiratory distress syndrome group (RDS). (It scores between 4 and 7 at age 4 hours. The 19 a in the were selected the basis of clinical RDS group on happened that there were no infants whose respira- distress score between 4 and 7 at the same age. As can tory distress resolved between 18 and 30 hours of be seen from Table II, the mean birthweight, gestational age.) age, and five-minute Apgar scores of both groups of Procedures Jnd Methods infants are comparable. Four of the RDS infants Infants who manifested idiopathic respiratory distress subsequently died. None of the infants had clinical were clinically evaluated on the basis of a scoring system findings suggestive of aspiration syndrome (Schaffer, given in Table I. This scoring system, 0 to 10, has 1960), pneumothorax, or pneumomediastinum (Malan significant linear correlation with the alveolar-arterial and Heese, 1966). Po2 gradient, arterial hydrogen ion concentration, and Paco2 (Downes, Vidyasagar, Morrow, and Boggs, 1967). TABLE I If, over a 2-hour period, an infant maintained a score of Clinical Respiratory Distress Scoring System 4 or more, and other causes of respiratory distress were not evident, a presumptive diagnosis of idiopathic 2 1 0 Score respiratory distress syndrome was made. Umbilical Respiratory rate artery catheterization was then performed and the 80 or apnoea 60-80 60 (breaths/min.) In air In 40% 02 None .. Cyanosis catheter inserted 10 to 14 cm., depending on the length Retractions Moderate-severe Mild None .. of the infant, so that its distal tip was in the thoracic Grunting Audible without Audible with .. None stethoscope stethoscope aorta below the ductus arteriosus (Dunn, 1966). After Air entry
Received March 10, 1967. * Supported by NIH Grants, Nos. NB 04828 and NB 02367.

(crying)

..

Clear

Delayed or
decreased

Barely audible

659

660

Downes, Arya, Morrow, and Boggs

Clinical and Arterial Blood Data: Transient Respiratory Distress Syndrome

(wk.)

Apgar at 5 min.
2-8 hr.

RDS Score
8-18 hr.
3 2 1 2 3 3
1 3 3 2 1 3

P.02 (mm. Hg)

F,02

F,02 100%
2-8 hr.
-

F,02

210/

2-8 hr.
-

20-30 hr.

TRD

1 2 3 4 5 6 7 8 9 10 11 12 .

.2070 .1620 .2100 .1820 .2390 .2590 .2250 .1420 .1720 .1590 .1480 .1770
1901 12 11
2017 19 141 n.s. 2080 18 67 t

35 32 32 38 ? 35 37 30 31 31 30 32 33 11 34 16

8 7 5 10 10 9 8 ?
9 5 8

5 5 4 4 7 6 4 4 4 6 7 7 5-4 12
-

3 0
1 2 3 1 3 2 2

0 0

61 55 49 76 78 70 73 63 25
-

390 435 345 305 285 270 390 310 74 67 287 10 28

76 60
67 60
-

80
-

51 63
-

74 65 8 3-8

Mean .. Number S.E.

8 10
-

2 2 12
-

12

1 6

61 9 5-5 46 17 13 <0-02 79 9

RDS Mean .. .. .. Number.. .. .. S.E. TRD vs RDS: p .. Controls Mean Number S.E. .. TRD vs Normal: p ..
*

0*8 na.
35 17 1
at

8 16 -

5-8 19 0

5-3 19 0

5-1 15 0

_ 70 9 48
n.s.

62
n.s.

APaCO2

(PaCO2 at 2-8 hr.) (PaCo2

8-15 hr.).

t Base excess at 2-8 hr. before intravenous NaHCO3.

Both groups of infants received equivalent therapy with high oxygen concentrations, sufficient to maintain the Pao2 at 70 to 100 mm. Hg if possible, intravenous NaHCO3 in a dose calculated to correct the base deficit in order to maintain the arterial pH above 7 30, and an intravenous infusion of 5% glucose. The skin temperature was maintained at 36 h0 .50 C. In 17 premature infants, who were otherwise normal and were maintained at the neutral temperature, arterialized capillary blood provided control data for arterial pH, PaCo2, and Pao2. The mean PaOs values from arterialized blood agreed closely with the umbilical artery data in full-term infants at comparable ages (Prod'hom, Levison, Cherry, Drorbaugh, Hubbell, and Smith, 1964).

Results The initial clinical score, Pao2, and acid-base status for each patient were determined at 2-8 hours, 8-18 hours, and 20-30 hours of age. The results of these serial studies are presented in Table II. The TRD infants had a mean initial score of 5. At an average age of 12 hours this had decreased below 4 in every case with a mean score of 2. By an average age of 24 hours the mean score further decreased to 1 -5 (Table II). The infants in the RDS group had an initial mean score of 6 which decreased to 5 by the average age of 12 hours, and all of these infants still had a score of 4 or greater beyond age 30 hours.

The initial PaO2 values obtained during inhalation of 1000% 02 had a mean of 287 mm. Hg in the TRD group and 251 mm. Hg in the RDS group. These means were not significantly different. However, after breathing room air for at least 10 minutes, the TRD group had a mean PaO2 of 61 mm. Hg, compared to a mean of 46 mm. Hg in the RDS group. These means are significantly different (p <0 02). The mean Pao2 of the TRD group at 2-8 and 20-30 hours during air breathing is not significantly different from that of the control premature infants. Therefore, the PaO2 during air breathing may prove to be a useful though not absolute guide in distinguishing these two groups of infants early in their illness. The TRD infants had an initial mean PaCo2 of 62 mm. Hg, hardly different from the mean of 57 mm. Hg in the RDS group. By an average age of 12 hours the mean PaCO2 had decreased to 41 mm. Hg in the TRD group, a reduction of 21 mm. Hg in only 8 hours. This PaCO2 is significantly lower (p<0 05) than the mean of 53 mm. Hg in the RDS group. The mean PaCo2 remained at 41 mm. Hg in the TRD group at 24 hours of age, a level again significantly lower (p <0 05) than the mean of 51 mm. Hg in the RDS group, but significantly higher (p<0 001) than in the controls.

Transient Respiratory Distress Syndrome in the Newborn

661

Il
Respiratory Distress Syndrome, and Control Premature Newborns
(

PaCO2 (mm. Hg)

A\P,tC02*
20-30 hr. 8-18 hr.

pH
I~~~~~~~~~~~~~~~~~~~

Base Excess (mEq,/l-)t

2-8 hr.

8-18 hr.

2-8 hr.

8-18 hr.

2-8 hr.

8-18 hr.

20-30 hr.
+2-8 +5 -5

77 47 61 61 53
I so

48

33 37 38 44 49 42
14 1)

48 46 60 92
Q0

45 40 38 56
A1 ,,

42 43 40 42 45 39 'Ar 0,) 36
34 38 48
47 =.

- 15 -40 _9 -17 - 12 -11

7 -26 7 -17 7 -25 7 -22 7 -16 7 -25

7 -39 7 -43 7 -32 7 -36 7 -34 7 -39

7 -19 7 -28 7 -26 6 -99

7 -36 7 -34
7 -35

7 -25

%Q

vo'

7 -.AQ

7 / -AA *4u 7 -43 7 -36 7 -38 7 -41

7 -41 7 -44 7-34 7 -40 7 -36 7 -42

-3 -4 +1 -5 -5-7 -1 -8 -5-3 -2 -9 )o.A -Z-U

-4 -0 +1-5 5-5 +1 -2 + 1 -7 +1 -8 A
_'7.
+ 0-2

- 3-4 +1 -8 + 1-5 +1-6

-A.4

10*9 4-2 0-3 -6-4

-3 -3 -3 -5 -2 -7
t A -

''L

-A .1 _, -'-L

+0-3 -5-0 -1-5 5 +6+ :

62 12

5-0

41 12
2-0

41 12
1-0

-21

12 4 7

7 -20 12
0-03

7 36 12
0-01

7 -39 12
0-01

-3-8 12
0-9

-1 -6 12
0-9

+0-9 12

1.0

57 19 5-5 n.s.
38 17 1-6

53 19 4-8 <0 05
33 6 2-8 <0-05

51 16 4-8 <0-05
32 17 1-0 <0-001

-4-5 19 4-6 <0-02

7-19 19 0-02 n.s.

7-30 19 0-02 <0-02

<0-01

7-31 16 0-02
7-37 17 0-01 n.s.

-5-9 19 0 6 n.s. -6-4 17 0-4 <0-02

-1 -3 19 0 9
n.s.

-0-2
n.s.

16 1-2

<0*001

-6-0 6 0-4 <0-001

-5 7 17 0-5 <0-001

Values corrected for effect of raised PaCO2 (Dell et al., 1966).

non-significant.

The initial mean arterial pH of 7 * 20 in the TRD group was essentially the same as that of 7-19 in the RDS group. By mean age 12 hours, the pH of the TRD group had risen to 7-36 following intravenous NaHCO3. This level was equal to that of the control premature infants at this age, and significantly higher (p <0 02) than the mean of 7 30 in the RDS group. The persistence of a lower pH in the RDS group was attributable to the high Paco2. At age 24 hours the TRD group had a mean pH of 7 39, a value again equal to that of control infants, and significantly higher (p <0 01) than the mean of 7-31 in the RDS group. The mean initial base deficit (or negative base excess) of the TRD group was 3 *8 mEq/l., a value not significantly less than the mean of 5 9 mEq/l. in the RDS group. After the initial sample, the TRD and RDS infants received a single intravenous injection or rapid infusion of NaHCO3 in a dose calculated to correct completely the base deficit, and to raise the arterial pH above 7 30. Subsequently, both groups received intermittent injections of NaHCO3 calculated to keep the arterial pH above 7 * 30. This therapy resulted in a negligible average base deficit in both groups of patients at 8-15 and 20-30 hours of age. The mean base deficit of about 6 mEq/l. in our control premature infants

throughout the period 0-30 hours compares with a value of about 4 mEq/l. found by Bucci, Scalamandre, Savignoni, and Mendicini (1965) and of about 2 mEq/l. found by Malan, Evans, and Heese (1965). Chest x-ray films obtained in 6 of the TRD infants showed hyperaeration and, in 2 cases, the reticulo-granular pattern usually associated with RDS. As can be seen from Table II, Cases 11 and 12 in the TRD group had initial clinical scores of 7, a Pao2 less than 100 mm. Hg in 100% 02, and an arterial pH value of 7 * 08 and 6 * 99. The following description of one of these exceptional cases illustrates how rapidly recovery can occur when the infant receives the therapy outlined above.
Case Report (Case 12) This 1770 g. infant was the product of an apparently normal pregnancy, except for premature rupture of the membranes at 32 weeks' gestation, followed within 60 hours by an uncomplicated vaginal delivery. The amniotic fluid was normal and no resuscitation was required. The 1- and 5-minute Apgar scores were 8. At 1 hour, the baby had a clinical respiratory distress score of 6, despite an inspired 02 concentration of 50% and restoration of skin temperature to 35. 5 C. By

662

Downes, Arva, Morrow, and Boggs

of patients could lead to misinterpretation of their dramatic improvement as an effect of the new therapy. Summary Twelve premature newborns at age 4 hours had respiratory distress syndrome which, though clinically and biochemically of moderate to severe degree, had practically disappeared by 18 hours. Infants with this transient form of respiratory distress (TRD) could not be distinguished at age 4 hours from a group comparable in weight and gestational age with typical respiratory distress syndrome (RDS) persisting beyond age 30 hours, and sometimes proving fatal. Arterial P02 during air breathing tended to be somewhat higher in the TRD group, but arterial pH, Pco2, and base deficit initially showed changes of similar degree in both TRD and RDS groups. Both groups received equivalent therapy, including oxygen and intravenous sodium bicarbonate. Whereas in the TRD group by age 18 hours the average arterial Comments Pco2 had fallen by 21 mm. Hg and pH had risen to Boston, Geller, and Smith (1966), in a study of control levels, in the RDS group, a moderately 51 infants with RDS, divided their patients at about severe respiratory acidosis persisted throughout 4 hours of age into a 'high risk' group (mortality the first 30 hours. The existence of a transient form of respiratory 74-81%) and a 'low risk' group, on the basis of an arterial pH above (and equal to) or below 7 * 20, or a distress should be taken into account when any new PaO2 above (and equal to) or below 100 mm. Hg therapy for RDS is to be evaluated. during 100% 02 breathing. Using the arterial pH criterion, one-half of our TRD infants would have REFERENCES been classified in the 'high risk' group, whereas only Astrup, P., J0rgensen, K., Siggaard Andersen, O., and Engel, K. (1960). The acid-base metabolism: a new approach. Lancet, two (Cases 11 and 12) would have been so designated1, 1035. on the basis of the PaO2. This experience casts Avery, M. E., Gatewood, 0. B., and Bramley, G. (1966). Transient tachypnea of newborn. Amer. J. Dis. Child., 111, 380. doubt on the arterial pH as a reliable early criterion Boston, R. W., Geller, F., and Smith, C. A. (1966). Arterial blood for the assignment of risk. gas tensions and acid-base balance in the management of the respiratory distress syndrome. J. Pediat., 68, 74. 2 in TRD Only infants the group had 5-minute Bucci, G., Scalamandre, A., Savignoni, P. G., and Mendicini, M. Apgar scores below 7, and though this does not (1965). Acid-base status of 'normal' premature infants in the eliminate intrauterine asphyxia during labour as a first week of life. Biol. Neonat. (Basel), 8, 81. R., Engel, K., and Winters, R. W. (1966). A computer model cause of transient respiratory distress, it seems Dell,for the in vivo titration curve and its relevance to the acid-base unlikely that the asphyxia was extreme at the time changes in respiratory distress syndrome (RDS). Abstracts of the American Pediatric Society Meeting, p. 13. of delivery. A low birthweight for gestational age J. J., Vidyasagar, D., Morrow, G. M., and Boggs, T. R. occurred in only 2 of the TRD infants (Cases 4 and Downes, (1967). Clinical score with acid-base and blood gas correlations in RDS. Abstracts of the Society for Pediatric Research, 7), making this an improbable predisposing factor. p. 159. The infants with transient tachypnoea, described Dunn, P. M. (1966). Localization of umbilical catheter by postrecently by Avery, Gatewood, and Bramley (1966), mortem measurement. Arch. Dis. Childh., 41, 69. A. F., Evans, A., and Heese, H. de V. (1965). Serial Malan, are not comparable to our patients. acid-base determinations in normal premature and full-term We conclude that there are some infants who infants during the first 72 hours of life. ibid., 40, 645. and Heese, H. de V. (1966). Spontaneous pneumothorax in initially manifest the clinical and biochemical -,the newborn. Acta paediat. (Uppsala), 55, 224. picture of moderate or severe respiratory distress, Prod'hom, L. S., Levison, H., Cherry, R. B., Drorbaugh, J. E., Hubbell, J. P., Jr., and Smith, C. A. (1964). Adjustment of but who recover within the first 18 hours of life ventilation, intrapulmonary gas exchange, and acid-base balance after therapy with oxygen, sodium bicarbonate, and during the first day of life. Pediatrics, 33, 682. intravenous fluids. In any investigation of a new Schaffer, A. J. (1960). Diseases of the Newborn, p. 76. W. B. Saunders, Philadelphia. form of therapy to be used early in the respiratory Siggaard Andersen, 0. (1962). The pH-log PCO2 blood acid-base distress syndrome, failure to recognize this group nomogram revised. Scand. J. clin. Lab. Invest.,.14, 598.

3 hours, the clinical score had risen to 7. Analysis of arterial blood at that time gave a PaCO2 of 99 mm. Hg, a pH of 7 -08, and a base deficit of 4 mEq/l. The Pao2 was 67 mm. Hg during 100% 02 breathing. A Pao2 during air breathing was not obtained because of the clinical condition. The inspired oxygen concentration was subsequently maintained above 90%. At age 31 hours, an intravenous infusion of 5% glucose was started, with the immediate injection of 5 mEq NaHCO3, followed by the slow infusion of a further 2 mEq over the next 6 hours. There was rapid improvement, and at age 8 hours the inspired oxygen concentration could be reduced to 60%. At age 10 hours the clinical score had fallen to 3, associated with a decrease in PaCO2 to 41 mm. Hg, a reduction of 58 mm. Hg over 7 hours. Concomitantly, the arterial pH rose to 7 39 and the base deficit was completely corrected. The Pao2 increased to a level of 290 mm. Hg in 60% 02. At age 20 hours the infant had a clinical score of 0, and the PaO2 during air breathing was 74 mm. Hg, normal for this age, and the subsequent course was uneventful.