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Transcutaneous monitoring of oxygenation: What is normal?
Transcutaneous monitoring of oxygenation: What is normal? We examined 55 infants on 1t9 occasions, from birth to 6 months, to obtain normal data and to establish guidelines for the m a n a g e m e n t of oxygendependent infants with chronic lung disease. Transcutaneous oxygen tension (tcPo2) and saturation (tcSao2) were monitored during four states: awake, feeding, quiet sleep, and active sleep. Lowest values (mean • SD) for tcSao2 were recorded in a! l states during the first week of life: a w a k e 96.2% _+ 2.6%, feeding 91.2% • 3.7%, quie t sleep 93.2% • 2.9%, and active sleep 92.1% _+ 2.9%. After the first Week the results were affected b y state rather than age, with differences observed between a w a k e and feeding (P <0.0001), a w a k e and asleep (P <0.00001), and quiet sleep and active sleep (P <0.001). The findings for tcpo2 were less consistent and probably affected by the characteristics of skin. In the first week, values were as follows: a w a k e 83.5 _+ 10.1 mm Hg, feeding 73.4 • I0.I mm Hg, quiets!eep 78.5 • 10.9 mm Hg, and active Sleep 73.4 • 11.4 mm Hg. Subsequently, only the state effect remained, and significant differences existed between a w a k e and feeding (P ~0.0001) and a w a k e and asleep (P <0.00001). We conclude that transcutaneous blood gas measurements are affected b y state of the infant. (J PEDIATR1986;108:365-371)
Jacqueline Y. Q. Mok, M.D., F. John McLaughlin, M.B., D.Ch., Marjeta Pintar, B.Sc., R.N.,Hendrik Hak, M.D., Rudolfo Amaro-Galvez, M.D., and Henry Levison, M.D. From the Department of Pediatrics, The Hospital for Sick Children, Toronto
Sequential studies of respiratory rate measured in the same normal infants in the first 6 months of life show that this physiologic variable follows a specific pattern, being highest in the first week, then declining to 3 months, with no further changes.~ The increased resPiratory rate in the first week is attributed t o a pliable rib cage with resultant decrease in tidal volume. It is not unreasonable to postulate that changes in oxygenation will also occur with age. However, scant information exists on oxygen regulation from birth to 6 months, because until recently oxygen data could not be measured noninvasively. In our report of 11 term infants studied sequentially, transcutaneou s oxygen tension was found to rise significantly between 1 week and Submitted for publication July 1, 1985; accepted Aug. 28, 1985. Reprint requests: Henry Levison, M.D., The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
1 month of age. 2 The authors commented on the wide interand intrasubject variability, but the study group was small. tcP02 has an established role in the management of critically ill pediatri c patients 3 and those with cfironic lung disease4 or congenital heart disease? The technique is simple, noninvasive, and reliable, but has minor disadvantcPo2 tcSao2
Transcutaneous oxygen tension Transcutaneous oxygen saturation
tages in that the response time is slow, the electrode requires frequent recalibration, and repositioning is necessary to avoid thermal skin injury? Arterial oxygen saturation of hemoglobin can be measured continuously and directly by using a pulse oximeter, which has been evaluated in normal adults 7 and in critically ill pediatric patients), 9 A home oxygen program has existed at The Hospital for
365
366
M o k et al.
The Journal o f Pediatrics March 1986
T a b l e I. Clinical data in infants at time of monitoring
Monitoring interval
infant
Age (wk)
1 week 6 weeks 3 months 6 months
30 34 37 18
1 6 -+ 0.82 12.3 + 0.77 25.8 _+ 1.80
Skinfold (ram) 4.70 6.76 7.24 7.28
+ 1.03 _+ 1.45 • 1.60 + 1.12
Length (cm) 51.0 56.2 6t.3 69.5
+ 2.27 + 2.45 _+ 2.67 • 4.58
Weight (kg) 3.32 4.82 6.03 7.83
_+ 0.42 + 0.56 _+ 0.82 _+ 1.03
Study period (min) 50.8 73.8 69.9 77.7
_+ 16.2 + 21.1 + 22.5 • 32.9
Data represent mean _+SD.
lable
II. Interbaby variation
Age TcPoz (ram Hg) <1 week 6 weeks 3 months 6 months TcSaQ (%) <1 week 6 weeks 3 months 6 months
Asleep
Feeding
Quiet sleep
Active sleep
64.0-97.5 68.0-96.3 69.3-95.5 61.3-94.3
56.8-90.5 70.0-94.5 69.3-93.8 62.7-91.7
58.5-96.2 53.0-92.3 53.I-86.9 54.3-86.2
50.4-94.7 53.2-93.3 54.0-86.5 60.9-83.5
91.8-100 95.0-99.0 91.5-100 95.0-100
83.3-97.2 88.5-99.0 92.5-99.0 93.4-98.5
87.4-98.3 89.4-98.1 89.0-97.6 88.4-98.6
86.1-98.4 87.5-98.5
88.0-97.0 89.5-96.5
Data represent mean minimum and maximum values observed in 55 infants, at each age and state.
Sick Children, Toronto, for babies with chronic lung diseaseJ ~ Infants are weaned from oxygen when tcPoz is >60 m m Hg during all activities. This arbitrary level was chosen because no data are available on the optimum level of tcPo2 in the term infant, after the newborn period. The danger exists that some of the infants may be weaned from oxyge n too soon, with resultant hypoxic pulmonary vasoconstriction and cor pulmonal e. Moreover, chronic hypoxemia has been shown to have adverse effects on many aspects Of cognitive function." We therefore examined healthy term infants, to establish normal d a t a for tcPo2 and tcsao2 values during and after the neonatal period. We also assessed whether tcsao2 monitoring could be a s reliable as tcPo2 in these infants, to establish guidelines for the management of chronic lung disease in infants receiving supplemental oxygen. METHODS Fifty-five healthy infants (26 boys) without cardiorespiratory disorders were examined. Mean birth weight was 3.39 kg (range 2.05 to 4.50 kg), and gestational age 39.8 weeks (range 37 to 42 weeks). All infants were free of respiratory tract infections during and within 6 weeks of the study. Informed consent was obtained from parents, and the study was approved by the H u m a n Experimentation Committee of the hospital. Studies were performed in the first week of life while babies were in the newborn nursery. Parents brought
infants for further studies to the Sleep Laboratory of the hospital, at about 6 weeks, 3 months, and 6 months of age. All infants were seen during the day. Before each study, the baby's weight, length, and infrascapular skinfold thickness were obtained (Table I). The tcPo2 electrode, tcSao2 sensor, and abdominal band were then applied. Observations were made by two observers in a dimly lit room, with the infant awake, feeding, and asleep. The infants slept unrestrained, either supine in the crib or held semisupine. Recording. tcPo 2 was monitored using a Servomed oxymonitor electrode (Litton Datamedix, Sharon, Mass.) heated to 44 ~ C and applied to the anterior chest wall. Readings were taken after 10 to 20 minutes, when a stable plateau was reached. A continuous digital and a graphic recording of tcPo2 were displayed. The electrode was calibrated in vitro before each study, using the zero solution and room air. The membrane was changed at least once per week. A pulse oximeter (Nellcor Inc., Hayward, Calif.) was used to measure tcSao2. The instrument probe was applied to the infant's palm or digit, and consisted of a lightemitting diode (wavelengths 660 to 940 rim) and a photo cell detector that measured the light absorption characteristics of oxygenate d hemoglobin on a pulsati!e basis. No calibration was required, tcSao2 values were calculated by a m!croprocessor and displayed digitally. A concomitant heart rate was also displayed. The instrument was operated
Volume 108 Number 3
on mode 2, which computed the beat-to-beat variation of tcSao~ and heart rate. Respiratory patterns were monitored using induction plethysmography (Respitrace, Ambulatory Monitoring Inc., Ardsley, N.Y.), ~2 with only an abdominal band applied. No attempt was made to calibrate th e recording of respiration. Sleep state was determined by one observer, using the criteria of Prechtl, ~3 categorizing behavioral pattern in conjunction with respiratory patterns. Quiet sleep was defined as a relaxed state with eyes closed without rapid eye movements, with regular respirations and no gross body movements except for occasional startles. Active sleep was recorded when rapid eye movements were observed with eyes closed, respirations were irregular, and frequent small movements of the limbs, face, and head occurred. When the criteria were not met, the baby was said to be in indeterminate sleep. All data (tcPo2, tcSao2, heart rate, and respiratory patterns) were continuously recorded on a four-channel recorder (Hewlett-Packard Co., Andover, Mass.) at a paper speed of 5 mm/sec. Apart from th e sleep states, all other behaviors, such as crying or startles and including nursing interventions, were charted on the paper. Data evaluation. To avoid interobserver variation, all records were analyzed by one person. Periods when the baby was crying or was handled were excluded from analysis. From the continuous record, four clearly defined states were usually noted: awake, feeding, quiet sleep, and active sleep. Data from indeterminate sleep are not presented. The mean tcPo2 and tcSao2 were noted for each minute, from which the mean values for each state were calculated for each baby. Subsequently, group means and standard error of the mean were computed. Statistical analysis. Statistical analysis was performed using the Statistical Library for the Hewlett-Packard Series 200 computers. Two-tailed independent sample Student t tests were used to compare differences between two samples. Developmental trends and the effects of state on tcPoz and tcSao2 were assessed with a two-way unbalanced analysis of variance. Treatment contrasts were applied for comparisons on a specified factor, with another factor held constant. RESULTS One hundred nineteen studies were performed in 55 infants. Thirty-eight (69%) underwent two or more studies. The wide variation in recordings obtained among the babies is shown in Table II, and was most apparent in tcPo2 data. Fig. 1 shows the group means for tcPo2 and tcSao2
Transcutaneous oxygenation
AWAKE
FEEDING
367
QUIET SLEEP
ACTIVE SLEEP
9-1s
16-~o
TRANSCUTANEOUS PO l (rnm Hg) 90
85
80
75
70
65
|
<1
4-s AGE (WEEKS)
TRANSCUTANEOUS S~JO~.(•) 100
99 98 97 96 95 94
93 92 91 9O
Q
<1
4-8
9-15
AGE(WEEKS)
16-50
Fig. 4. Mean _SEM tcPo2 (A) and tcSao2 (B) versus age.
plotted as a function of age and state. When group means for each age and state were compared, a trend emerged. In the first week of life, tcSa02 levels were lowest for all states, with little change thereafter, tcPoz levels in the first week were less consistent, being higher for awake and for asleep than at subsequent ages. Because tcP02 and tcSa02 showed state-related characteristics that appeared homogenous after the first week, two-way analysis of variance was performed for all ages, and then repeated when data for the first week were excluded. For all data, a significant interaction effect (P <0.05 and P <0.0005 for tcPoz and tcSa02, respectively) was seen between the age at study and the state of the infant. After the first week, analyses of variance showed that for both tcP02 and tcSa02, no interaction effect existed between age and state; age alone did not have an effect on the measurements, but significant state effects were seen (P <0.0000l). To assess the differences in tcPoz and tcSa02 with different states, multiple comparisons were performed
3 68
M o k et al.
The Journal of Pediatrics March 1986
1001 TcPO= (mmHg) 0/~
! ~
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~ Respirati~I ~ F i g . 2. tcPa02, tcSao2, heart rate, and respirations in a 6-week-old healthy infant, during quiet sleep (A), followinga sigh (B), during active sleep (C), and during periodic breathing (D).
using contrasts. For tcPo2, significant differences existed between awake and feeding (P <0.0001), and awake compared with asleep (P <0.00001). No significant difference was found between quiet and active sleep (P = 0.28). tcSao2 values were significantly different when awake was compared with feeding (P <0.00001), awake with asleep (P <0.00001), and quiet with active sleep (P <0.01). Variation with state, Fig. 2 shows samples from a representative sleep record of a 6-week-old baby. In all infants, a clearly demonstrable pattern was noted during quiet sleep (Fig. 2, A) for tcSao2, heart rate, and respirations. In quiet sleep these values remained regular and stable, except following a sigh (Fig. 2, B). The irregularity of respirations and fluctuations in tcSao2 were seen during active sleep (Fig. 2, C), with changes seldom reflected by tcPo2 measurements. Fluctuations were also seen during periodic breathing (Fig. 2, D), defined as three respiratory pauses of >__3 seconds, interrupted by respirations for <20 secondsJ 4 We observed periodic breathing in seven infants, on eight
occasions, at age 6 weeks (five infants) and 3 months (three infants). None was observed during the first week or at 6 months. It occurred in quiet sleep as well as active sleep, with the total time spent ranging from 23 seconds to 61/2 minutes. During an episode of periodic breathing, tcSao2 fell 25.9% ___7.4% from baseline, with tcPo2 falling 17.3% _+ 5.2%. The tcPo2 recording tended to drift downward rather than reflect instantaneous changes of periodic breathing. The duration of tcSao2 below 85% ranged from 3 to 131 seconds. A typical record obtained within the first week during feeding is shown in Fig. 3. Of 19 babies who fed during the first week, all had a decrease in oxygenation at the start of feeding. Mean decline in tcPo2 was 17% + 10%, with a decrease of 20% _+ 11% from baseline seen in tcSao2. With continued feeding, oxygenation improved (Fig. 3, B). At 6 weeks, deoxygenation still occurred at the start of a feed, observed in 24 of 26 babies who fed. tcPo2 levels fell 10% • 9%, and tcSao2 16% _ 9% from baseline.
Volume 1 0 8 Number 3
Transcutaneous oxygenation
369
TcP02 100 1 (mmHg) 0 i/
~"" -
ROOm
TeSa02
(%)
J ~ | 50 ~-
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s sec
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100 1 TcP02 (mmHg) /
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Fig. 2. Continued.
DISCUSSION Three relatively discrete stages of dev'elopent have been recognized during studies of respiratory rate from birth to 6 months of life1: the newborn period, early infancy (1 to 3 months), and later infancy. The first week of life was considered unlike any subsequent age. Our data confirm these observations, so we chose to examine our data from the first week separately. From 1 to 6 weeks, oxygenation improved in all states. Values were clearly related to state, with the highest values observed during wakefulness. From 6 weeks on, the infants appeared stable, although the state effect remained. During the first week of fife, our mean tcPo2 for quiet sleep~and active sleep are comparable to those of 77.0 and 70.5 mm Hg, respectively, obtained by Martin et alJ 5 However, another study 2 reported 11 infants with slightly lower values of about 67.5 mm Hg for both quiet sleep and active sleep. Our skinfold thickness data (Table I) show the significant elevation in this measurement from week 1 to week 6, with little increase thereafter. We were unable to correlate skinfold thickness with tcPao2, because we
realized that on the basis of our data, if we correlated skinfold thickness with tcPa02 measurements while awake, we would find no correlation. However, if we chose to correlate skinfold thickness with tcPao2 measurements during quiet sleep, we would find a positive correlation (Fig. 1). The interdependence of sleep state and respiratory control mechanisms in newborn infants is well documented.16, iv During active sleep, diaphragmatic and intercostal muscle tone is lost. In addition to a decrease in functional residual capacity, there is paradoxical "sucking in" of the rib cage; these explain the decline in oxygenation during active sleep in our babies in the first week, an observation also documented by others} .'5 Our infants continued to show significant desaturation in sleep compared with the awake state, even at 6 months (toP02 difference 7 mm Hg, tcSa02 2.8%). Previous work in normal adolescents, using ear oximetry, showed a tcSao2 decrease of only 1.1% from awake to asleep.IS The minimal decrease observed in adolescents and the higher baseline levels when compared with infants are presumably the
37 0
M o k et al.
The Journal o f Pediatrics March 1986
'~176 t
(mmHg) 0
TcSa02
I
~
(o/o)
I
I
- !:: .
so~
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'~
-
-"
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I
Respiration 1 ~
Fig. 3. Continuous record obtained during feeding in 1-week-old infant. Note recovery in oxygenation with continued feeding. result of a more stable rib cage and efficient respiratory pump. Apart from the effect of state on oxygenation, our data also show a wide variation between babies in the same state. Logistically, it was impossible to study all states sequentially in many infants. However, subanalyses performed in some infants who were studied in more than one state on more than one occasion showed that withinsubject variation was less than intersubject variation. Although periodic breathing has been reported to be a risk factor in sudden infant death, TM it is also recognized in normal preterm and term infants. '9-z~The incidence in term babies within the first 48 hours of life was reported as 25%. 19 During the first week our babies were usually studied after 48 hours, and this might explain the fact that no periodic breathing was observed. In our older infants, the incidence of periodic breathing was 14.5%, which is lower than that described by Richards et al. 2~ However, these authors used less stringent criteria to define periodic breathing, so that 69% to 80% of infants were reported to have periodic breathing during the first 6 months. The striking changes in tcSa0z that we observed during periodic breathing have not been previously documented. Alterations in breathing pattern during oral feeding
have been described in preterm 2z and, more recently, in term infants.23 We observed breathing patterns similar to those described by Mathew et al., 23 but cannot comment in detail because our study was not designed to measure ventilation. Of note, however, it the marked decline in oxygenation at the start of feeding seen in healthy babies in the first week of life. This finding supports previous work in experimental animals and infants indicating that carotid body function is not fully mature at birth. 24'25 Maturity with postnatal age is seen by the smaller decline in oxygenation from 6 weeks on. Our data also illustrate the dangers of oral feeding in babies with cardiorespiratory disorders. Our study was limited in that physiologic means were not used to stage sleep; nevertheless, behavioral observation, documented by one person, in conjunction with respiratory patterns, probably provide a reasonably accurate assessment of sleep state. We have found tcSao2 monitoring to be more sensitive than tcPo2, as it reflected events on a pulsatile basis, tcSao2 was also more accurate because it is not affected by skin characteristics or electrode temperature. The only disadvantage of the tcSao2 sensor is its extreme sensitivity to movement. In an active
Volume 108 Number 3
baby, m o v e m e n t artifacts are sensed. This problem is usually overcome d u r i n g sleep; otherwise the i n s t r u m e n t can be operated on a less sensitive mode. In applying these data to babies with chronic lung diseas e and oxygen dependency, account must be t a k e n of the wide r a n g e of values in normal babies, T h e fact t h a t in quiet sleep tcP02 levels <55 m m Hg were observed in some infants suggests t h a t our a r b i t r a r y level of 60 m m H g for 0xygen-dependent babies m a y be too high. T h e i m p o r t a n c e of considering states of the infant, whether monitoring oxygenation or evaluating ventilation, is apparent. We thank Mary Corey for assistance with statistical analysis; and all the infants and parents, who willingly participated in the study. REFERENCES 1. Hoppenbrouwers T, Harper RM, Hodgman JE, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life. II. Respiratory rate and variability as a function of state. Pediatr Res 1978;12:120125. 2. Carse EA, Wilkinson AR, Whyte PL, Henderson-Smart D J, Johnson P. Oxygen and carbon dioxide tensions, breathing and heart rate in normal infants during the first six months of life. J Dev Physiol 1981;3:85-100. 3. Huch R, Huch A, Albani M, Gabriel M, Schulte FJ, Wolf H, Rupprath G, Emmrich P, Stechele U, Duc G, Bucher H. Transcutaneous Po2 monitoring in routine management of infants and children with cardi0respiratory problems. Pediatrics 1976;57:681-690. 4. Philip AGS, Peabody JL, Lucey JF. Transcutaneous Po2 monitoring in the home management of bronchopulmonary dysplasia. Pediatrics 1978;61:655-657. 5. Gidding SS, Rosenthal A, Moorehead C. Transcutaneous oxygen monitoring: its use in the treatment of outpatients with congenital heart disease. Am J Dis Child 1985;139:288291. 6. AsonYe UO, Vidyasagar D. Clinical application of continuous transcutaneous Po2 monitoring. In: Lauersen NH, Hochberg H, eds. Clinical perinatal biochemica mon toting. Baltimore: Williams & Wilkins, 1981:205-2t9. 7. Yelderman M, New W Jr. Evaluation of pulse oximetry. Anesthesiology 1983;59:349-352. 8. Deckardt R, Steward DJ. Non-inyasive arterial hemoglobin oxygen situation versus transcutaneous oxygen monitoring in the preterm infant. Crit Care Med 1984;12:935-939. 9. Fanconi S, Doherty P, Edmonds JF, Barker GA, Bohn DJ. Pulse oximetry in pediatric intensive Care: comparison with measured saturations and transcataneous oxyget~ tension. J PEDIATR 198,5;107 362-366
Transcutaneous oxygenation
37 1
10. Campbell AN, Zarfin Y, Groenveld M, Bryan MH. Low flow oxygen therapy in infants. Arch Dis Child I983;58:795-798. 11. Ncwburger JW, Silbert AR, Buckley LP, Fyler DC. Cognitive function an d age at repair of transpositio n of the great arteries in children. N Engl J Med 1984;310:1495-1499. 12. Duffty P, Sprier L, Bryan MH, Bryan MH, Bryan AC. Respiratory induction plethysmography (Respitrace): an evaluation of its use in the infant. Am Rev Respir Dis 1981 ; 123:542-546. 13. Prechtt HFR. The behavioural states of the newborn infant (a review): Brain Res 1974;76:185-212~ 14. Kelly DH, Shannon DC. Periodic breathing in infants with near miss sudden infant death syndrome. Pediatrics 1979;63:355-360. 15. Martin R J, Okken A, Rubin D. Arterial oxygen tension during active and quiet sleep in the normai neonate. J PEDIATR 1979;94:271-274. 16. Finer NN, Abroms IF, Taeusch HW Jr. Ventilation and sleep states in newborn infants. J PEDIATR 1976;89:100-108. 17. Muller NL, Gulston D, Cad e D, Whitton J, Froese A B, Bryan MH, Bryan AC. Diaphragmatic muscle fatigue in the newborn. J Appl Physiol 1979;46:688-695. 18. Tabachnik E, Multer NL, Bryan AC, Levison H. Changes in ventilation and chest wall mechanics during sleep in normal adolescents. J AppI Physiol 1981 ;51:557-564. 19. Fenner A; Schalk U, Hoenicke H, Wendenburg A, Roehling T. periodic breathing in premature and neonatal babies: incidence, breathing pattern, respiratory gas tensions, response to changes in the composition of ambient air. Pediatr Res 1973;7:174-183. 20. Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life. Ill. Incidence of apnea and periodic breathing. Pediatrics 1977;60:4J 8-425. 21. R~chards JM, Alexander JR, Shinebourne EA, de Swiet M, Wilson A J, Southall DP. Sequential 22 hour profiles of breathing patterns and heart rate in 110 full-term infants during their first 6 months of life. Pediatrics 1984;74:763777. 22. Shivapuri CR, Martin R J, Carlo WA, Fanaroff AA. Decreased ventilation in preterm infants during oral feeding. J PED~Aa'R 1983;!03:285-289. 23. Matthew OP, Clark ML, Pronske ML, Luna-Solarzano HG, Peterson MD. Breathing pattern and ventilation during oral feeding in term newborn infants. J PEDIA'rR 1985;106:810813. 24. Blanco CE, Dawes GS, Hanson MA, MczCooke HB. The resl~onse to hypoxia of arterial chemoreceptors in fetal sheep and newborn lambs. J PhysioI (Lond) 1984;351:25-37. 25. Gurwitz D, Spriet LL, Bryan MH, Bryan AC. Carotid body function in siblings of S1DS [abstract]. Pediatr Res I980;14:643.
Jacqueline Y. Q. Mok, M.D., F. John McLaughlin, M.B., D.Ch., Marjeta Pintar, B.Sc., R.N.,Hendrik Hak, M.D., Rudolfo Amaro-Galvez, M.D., and Henry Levison, M.D. From the Department of Pediatrics, The Hospital for Sick Children, Toronto
Sequential studies of respiratory rate measured in the same normal infants in the first 6 months of life show that this physiologic variable follows a specific pattern, being highest in the first week, then declining to 3 months, with no further changes.~ The increased resPiratory rate in the first week is attributed t o a pliable rib cage with resultant decrease in tidal volume. It is not unreasonable to postulate that changes in oxygenation will also occur with age. However, scant information exists on oxygen regulation from birth to 6 months, because until recently oxygen data could not be measured noninvasively. In our report of 11 term infants studied sequentially, transcutaneou s oxygen tension was found to rise significantly between 1 week and Submitted for publication July 1, 1985; accepted Aug. 28, 1985. Reprint requests: Henry Levison, M.D., The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
1 month of age. 2 The authors commented on the wide interand intrasubject variability, but the study group was small. tcP02 has an established role in the management of critically ill pediatri c patients 3 and those with cfironic lung disease4 or congenital heart disease? The technique is simple, noninvasive, and reliable, but has minor disadvantcPo2 tcSao2
Transcutaneous oxygen tension Transcutaneous oxygen saturation
tages in that the response time is slow, the electrode requires frequent recalibration, and repositioning is necessary to avoid thermal skin injury? Arterial oxygen saturation of hemoglobin can be measured continuously and directly by using a pulse oximeter, which has been evaluated in normal adults 7 and in critically ill pediatric patients), 9 A home oxygen program has existed at The Hospital for
365
366
M o k et al.
The Journal o f Pediatrics March 1986
T a b l e I. Clinical data in infants at time of monitoring
Monitoring interval
infant
Age (wk)
1 week 6 weeks 3 months 6 months
30 34 37 18
1 6 -+ 0.82 12.3 + 0.77 25.8 _+ 1.80
Skinfold (ram) 4.70 6.76 7.24 7.28
+ 1.03 _+ 1.45 • 1.60 + 1.12
Length (cm) 51.0 56.2 6t.3 69.5
+ 2.27 + 2.45 _+ 2.67 • 4.58
Weight (kg) 3.32 4.82 6.03 7.83
_+ 0.42 + 0.56 _+ 0.82 _+ 1.03
Study period (min) 50.8 73.8 69.9 77.7
_+ 16.2 + 21.1 + 22.5 • 32.9
Data represent mean _+SD.
lable
II. Interbaby variation
Age TcPoz (ram Hg) <1 week 6 weeks 3 months 6 months TcSaQ (%) <1 week 6 weeks 3 months 6 months
Asleep
Feeding
Quiet sleep
Active sleep
64.0-97.5 68.0-96.3 69.3-95.5 61.3-94.3
56.8-90.5 70.0-94.5 69.3-93.8 62.7-91.7
58.5-96.2 53.0-92.3 53.I-86.9 54.3-86.2
50.4-94.7 53.2-93.3 54.0-86.5 60.9-83.5
91.8-100 95.0-99.0 91.5-100 95.0-100
83.3-97.2 88.5-99.0 92.5-99.0 93.4-98.5
87.4-98.3 89.4-98.1 89.0-97.6 88.4-98.6
86.1-98.4 87.5-98.5
88.0-97.0 89.5-96.5
Data represent mean minimum and maximum values observed in 55 infants, at each age and state.
Sick Children, Toronto, for babies with chronic lung diseaseJ ~ Infants are weaned from oxygen when tcPoz is >60 m m Hg during all activities. This arbitrary level was chosen because no data are available on the optimum level of tcPo2 in the term infant, after the newborn period. The danger exists that some of the infants may be weaned from oxyge n too soon, with resultant hypoxic pulmonary vasoconstriction and cor pulmonal e. Moreover, chronic hypoxemia has been shown to have adverse effects on many aspects Of cognitive function." We therefore examined healthy term infants, to establish normal d a t a for tcPo2 and tcsao2 values during and after the neonatal period. We also assessed whether tcsao2 monitoring could be a s reliable as tcPo2 in these infants, to establish guidelines for the management of chronic lung disease in infants receiving supplemental oxygen. METHODS Fifty-five healthy infants (26 boys) without cardiorespiratory disorders were examined. Mean birth weight was 3.39 kg (range 2.05 to 4.50 kg), and gestational age 39.8 weeks (range 37 to 42 weeks). All infants were free of respiratory tract infections during and within 6 weeks of the study. Informed consent was obtained from parents, and the study was approved by the H u m a n Experimentation Committee of the hospital. Studies were performed in the first week of life while babies were in the newborn nursery. Parents brought
infants for further studies to the Sleep Laboratory of the hospital, at about 6 weeks, 3 months, and 6 months of age. All infants were seen during the day. Before each study, the baby's weight, length, and infrascapular skinfold thickness were obtained (Table I). The tcPo2 electrode, tcSao2 sensor, and abdominal band were then applied. Observations were made by two observers in a dimly lit room, with the infant awake, feeding, and asleep. The infants slept unrestrained, either supine in the crib or held semisupine. Recording. tcPo 2 was monitored using a Servomed oxymonitor electrode (Litton Datamedix, Sharon, Mass.) heated to 44 ~ C and applied to the anterior chest wall. Readings were taken after 10 to 20 minutes, when a stable plateau was reached. A continuous digital and a graphic recording of tcPo2 were displayed. The electrode was calibrated in vitro before each study, using the zero solution and room air. The membrane was changed at least once per week. A pulse oximeter (Nellcor Inc., Hayward, Calif.) was used to measure tcSao2. The instrument probe was applied to the infant's palm or digit, and consisted of a lightemitting diode (wavelengths 660 to 940 rim) and a photo cell detector that measured the light absorption characteristics of oxygenate d hemoglobin on a pulsati!e basis. No calibration was required, tcSao2 values were calculated by a m!croprocessor and displayed digitally. A concomitant heart rate was also displayed. The instrument was operated
Volume 108 Number 3
on mode 2, which computed the beat-to-beat variation of tcSao~ and heart rate. Respiratory patterns were monitored using induction plethysmography (Respitrace, Ambulatory Monitoring Inc., Ardsley, N.Y.), ~2 with only an abdominal band applied. No attempt was made to calibrate th e recording of respiration. Sleep state was determined by one observer, using the criteria of Prechtl, ~3 categorizing behavioral pattern in conjunction with respiratory patterns. Quiet sleep was defined as a relaxed state with eyes closed without rapid eye movements, with regular respirations and no gross body movements except for occasional startles. Active sleep was recorded when rapid eye movements were observed with eyes closed, respirations were irregular, and frequent small movements of the limbs, face, and head occurred. When the criteria were not met, the baby was said to be in indeterminate sleep. All data (tcPo2, tcSao2, heart rate, and respiratory patterns) were continuously recorded on a four-channel recorder (Hewlett-Packard Co., Andover, Mass.) at a paper speed of 5 mm/sec. Apart from th e sleep states, all other behaviors, such as crying or startles and including nursing interventions, were charted on the paper. Data evaluation. To avoid interobserver variation, all records were analyzed by one person. Periods when the baby was crying or was handled were excluded from analysis. From the continuous record, four clearly defined states were usually noted: awake, feeding, quiet sleep, and active sleep. Data from indeterminate sleep are not presented. The mean tcPo2 and tcSao2 were noted for each minute, from which the mean values for each state were calculated for each baby. Subsequently, group means and standard error of the mean were computed. Statistical analysis. Statistical analysis was performed using the Statistical Library for the Hewlett-Packard Series 200 computers. Two-tailed independent sample Student t tests were used to compare differences between two samples. Developmental trends and the effects of state on tcPoz and tcSao2 were assessed with a two-way unbalanced analysis of variance. Treatment contrasts were applied for comparisons on a specified factor, with another factor held constant. RESULTS One hundred nineteen studies were performed in 55 infants. Thirty-eight (69%) underwent two or more studies. The wide variation in recordings obtained among the babies is shown in Table II, and was most apparent in tcPo2 data. Fig. 1 shows the group means for tcPo2 and tcSao2
Transcutaneous oxygenation
AWAKE
FEEDING
367
QUIET SLEEP
ACTIVE SLEEP
9-1s
16-~o
TRANSCUTANEOUS PO l (rnm Hg) 90
85
80
75
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65
|
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TRANSCUTANEOUS S~JO~.(•) 100
99 98 97 96 95 94
93 92 91 9O
Q
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AGE(WEEKS)
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Fig. 4. Mean _SEM tcPo2 (A) and tcSao2 (B) versus age.
plotted as a function of age and state. When group means for each age and state were compared, a trend emerged. In the first week of life, tcSa02 levels were lowest for all states, with little change thereafter, tcPoz levels in the first week were less consistent, being higher for awake and for asleep than at subsequent ages. Because tcP02 and tcSa02 showed state-related characteristics that appeared homogenous after the first week, two-way analysis of variance was performed for all ages, and then repeated when data for the first week were excluded. For all data, a significant interaction effect (P <0.05 and P <0.0005 for tcPoz and tcSa02, respectively) was seen between the age at study and the state of the infant. After the first week, analyses of variance showed that for both tcP02 and tcSa02, no interaction effect existed between age and state; age alone did not have an effect on the measurements, but significant state effects were seen (P <0.0000l). To assess the differences in tcPoz and tcSa02 with different states, multiple comparisons were performed
3 68
M o k et al.
The Journal of Pediatrics March 1986
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using contrasts. For tcPo2, significant differences existed between awake and feeding (P <0.0001), and awake compared with asleep (P <0.00001). No significant difference was found between quiet and active sleep (P = 0.28). tcSao2 values were significantly different when awake was compared with feeding (P <0.00001), awake with asleep (P <0.00001), and quiet with active sleep (P <0.01). Variation with state, Fig. 2 shows samples from a representative sleep record of a 6-week-old baby. In all infants, a clearly demonstrable pattern was noted during quiet sleep (Fig. 2, A) for tcSao2, heart rate, and respirations. In quiet sleep these values remained regular and stable, except following a sigh (Fig. 2, B). The irregularity of respirations and fluctuations in tcSao2 were seen during active sleep (Fig. 2, C), with changes seldom reflected by tcPo2 measurements. Fluctuations were also seen during periodic breathing (Fig. 2, D), defined as three respiratory pauses of >__3 seconds, interrupted by respirations for <20 secondsJ 4 We observed periodic breathing in seven infants, on eight
occasions, at age 6 weeks (five infants) and 3 months (three infants). None was observed during the first week or at 6 months. It occurred in quiet sleep as well as active sleep, with the total time spent ranging from 23 seconds to 61/2 minutes. During an episode of periodic breathing, tcSao2 fell 25.9% ___7.4% from baseline, with tcPo2 falling 17.3% _+ 5.2%. The tcPo2 recording tended to drift downward rather than reflect instantaneous changes of periodic breathing. The duration of tcSao2 below 85% ranged from 3 to 131 seconds. A typical record obtained within the first week during feeding is shown in Fig. 3. Of 19 babies who fed during the first week, all had a decrease in oxygenation at the start of feeding. Mean decline in tcPo2 was 17% + 10%, with a decrease of 20% _+ 11% from baseline seen in tcSao2. With continued feeding, oxygenation improved (Fig. 3, B). At 6 weeks, deoxygenation still occurred at the start of a feed, observed in 24 of 26 babies who fed. tcPo2 levels fell 10% • 9%, and tcSao2 16% _ 9% from baseline.
Volume 1 0 8 Number 3
Transcutaneous oxygenation
369
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DISCUSSION Three relatively discrete stages of dev'elopent have been recognized during studies of respiratory rate from birth to 6 months of life1: the newborn period, early infancy (1 to 3 months), and later infancy. The first week of life was considered unlike any subsequent age. Our data confirm these observations, so we chose to examine our data from the first week separately. From 1 to 6 weeks, oxygenation improved in all states. Values were clearly related to state, with the highest values observed during wakefulness. From 6 weeks on, the infants appeared stable, although the state effect remained. During the first week of fife, our mean tcPo2 for quiet sleep~and active sleep are comparable to those of 77.0 and 70.5 mm Hg, respectively, obtained by Martin et alJ 5 However, another study 2 reported 11 infants with slightly lower values of about 67.5 mm Hg for both quiet sleep and active sleep. Our skinfold thickness data (Table I) show the significant elevation in this measurement from week 1 to week 6, with little increase thereafter. We were unable to correlate skinfold thickness with tcPao2, because we
realized that on the basis of our data, if we correlated skinfold thickness with tcPa02 measurements while awake, we would find no correlation. However, if we chose to correlate skinfold thickness with tcPao2 measurements during quiet sleep, we would find a positive correlation (Fig. 1). The interdependence of sleep state and respiratory control mechanisms in newborn infants is well documented.16, iv During active sleep, diaphragmatic and intercostal muscle tone is lost. In addition to a decrease in functional residual capacity, there is paradoxical "sucking in" of the rib cage; these explain the decline in oxygenation during active sleep in our babies in the first week, an observation also documented by others} .'5 Our infants continued to show significant desaturation in sleep compared with the awake state, even at 6 months (toP02 difference 7 mm Hg, tcSa02 2.8%). Previous work in normal adolescents, using ear oximetry, showed a tcSao2 decrease of only 1.1% from awake to asleep.IS The minimal decrease observed in adolescents and the higher baseline levels when compared with infants are presumably the
37 0
M o k et al.
The Journal o f Pediatrics March 1986
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Fig. 3. Continuous record obtained during feeding in 1-week-old infant. Note recovery in oxygenation with continued feeding. result of a more stable rib cage and efficient respiratory pump. Apart from the effect of state on oxygenation, our data also show a wide variation between babies in the same state. Logistically, it was impossible to study all states sequentially in many infants. However, subanalyses performed in some infants who were studied in more than one state on more than one occasion showed that withinsubject variation was less than intersubject variation. Although periodic breathing has been reported to be a risk factor in sudden infant death, TM it is also recognized in normal preterm and term infants. '9-z~The incidence in term babies within the first 48 hours of life was reported as 25%. 19 During the first week our babies were usually studied after 48 hours, and this might explain the fact that no periodic breathing was observed. In our older infants, the incidence of periodic breathing was 14.5%, which is lower than that described by Richards et al. 2~ However, these authors used less stringent criteria to define periodic breathing, so that 69% to 80% of infants were reported to have periodic breathing during the first 6 months. The striking changes in tcSa0z that we observed during periodic breathing have not been previously documented. Alterations in breathing pattern during oral feeding
have been described in preterm 2z and, more recently, in term infants.23 We observed breathing patterns similar to those described by Mathew et al., 23 but cannot comment in detail because our study was not designed to measure ventilation. Of note, however, it the marked decline in oxygenation at the start of feeding seen in healthy babies in the first week of life. This finding supports previous work in experimental animals and infants indicating that carotid body function is not fully mature at birth. 24'25 Maturity with postnatal age is seen by the smaller decline in oxygenation from 6 weeks on. Our data also illustrate the dangers of oral feeding in babies with cardiorespiratory disorders. Our study was limited in that physiologic means were not used to stage sleep; nevertheless, behavioral observation, documented by one person, in conjunction with respiratory patterns, probably provide a reasonably accurate assessment of sleep state. We have found tcSao2 monitoring to be more sensitive than tcPo2, as it reflected events on a pulsatile basis, tcSao2 was also more accurate because it is not affected by skin characteristics or electrode temperature. The only disadvantage of the tcSao2 sensor is its extreme sensitivity to movement. In an active
Volume 108 Number 3
baby, m o v e m e n t artifacts are sensed. This problem is usually overcome d u r i n g sleep; otherwise the i n s t r u m e n t can be operated on a less sensitive mode. In applying these data to babies with chronic lung diseas e and oxygen dependency, account must be t a k e n of the wide r a n g e of values in normal babies, T h e fact t h a t in quiet sleep tcP02 levels <55 m m Hg were observed in some infants suggests t h a t our a r b i t r a r y level of 60 m m H g for 0xygen-dependent babies m a y be too high. T h e i m p o r t a n c e of considering states of the infant, whether monitoring oxygenation or evaluating ventilation, is apparent. We thank Mary Corey for assistance with statistical analysis; and all the infants and parents, who willingly participated in the study. REFERENCES 1. Hoppenbrouwers T, Harper RM, Hodgman JE, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life. II. Respiratory rate and variability as a function of state. Pediatr Res 1978;12:120125. 2. Carse EA, Wilkinson AR, Whyte PL, Henderson-Smart D J, Johnson P. Oxygen and carbon dioxide tensions, breathing and heart rate in normal infants during the first six months of life. J Dev Physiol 1981;3:85-100. 3. Huch R, Huch A, Albani M, Gabriel M, Schulte FJ, Wolf H, Rupprath G, Emmrich P, Stechele U, Duc G, Bucher H. Transcutaneous Po2 monitoring in routine management of infants and children with cardi0respiratory problems. Pediatrics 1976;57:681-690. 4. Philip AGS, Peabody JL, Lucey JF. Transcutaneous Po2 monitoring in the home management of bronchopulmonary dysplasia. Pediatrics 1978;61:655-657. 5. Gidding SS, Rosenthal A, Moorehead C. Transcutaneous oxygen monitoring: its use in the treatment of outpatients with congenital heart disease. Am J Dis Child 1985;139:288291. 6. AsonYe UO, Vidyasagar D. Clinical application of continuous transcutaneous Po2 monitoring. In: Lauersen NH, Hochberg H, eds. Clinical perinatal biochemica mon toting. Baltimore: Williams & Wilkins, 1981:205-2t9. 7. Yelderman M, New W Jr. Evaluation of pulse oximetry. Anesthesiology 1983;59:349-352. 8. Deckardt R, Steward DJ. Non-inyasive arterial hemoglobin oxygen situation versus transcutaneous oxygen monitoring in the preterm infant. Crit Care Med 1984;12:935-939. 9. Fanconi S, Doherty P, Edmonds JF, Barker GA, Bohn DJ. Pulse oximetry in pediatric intensive Care: comparison with measured saturations and transcataneous oxyget~ tension. J PEDIATR 198,5;107 362-366
Transcutaneous oxygenation
37 1
10. Campbell AN, Zarfin Y, Groenveld M, Bryan MH. Low flow oxygen therapy in infants. Arch Dis Child I983;58:795-798. 11. Ncwburger JW, Silbert AR, Buckley LP, Fyler DC. Cognitive function an d age at repair of transpositio n of the great arteries in children. N Engl J Med 1984;310:1495-1499. 12. Duffty P, Sprier L, Bryan MH, Bryan MH, Bryan AC. Respiratory induction plethysmography (Respitrace): an evaluation of its use in the infant. Am Rev Respir Dis 1981 ; 123:542-546. 13. Prechtt HFR. The behavioural states of the newborn infant (a review): Brain Res 1974;76:185-212~ 14. Kelly DH, Shannon DC. Periodic breathing in infants with near miss sudden infant death syndrome. Pediatrics 1979;63:355-360. 15. Martin R J, Okken A, Rubin D. Arterial oxygen tension during active and quiet sleep in the normai neonate. J PEDIATR 1979;94:271-274. 16. Finer NN, Abroms IF, Taeusch HW Jr. Ventilation and sleep states in newborn infants. J PEDIATR 1976;89:100-108. 17. Muller NL, Gulston D, Cad e D, Whitton J, Froese A B, Bryan MH, Bryan AC. Diaphragmatic muscle fatigue in the newborn. J Appl Physiol 1979;46:688-695. 18. Tabachnik E, Multer NL, Bryan AC, Levison H. Changes in ventilation and chest wall mechanics during sleep in normal adolescents. J AppI Physiol 1981 ;51:557-564. 19. Fenner A; Schalk U, Hoenicke H, Wendenburg A, Roehling T. periodic breathing in premature and neonatal babies: incidence, breathing pattern, respiratory gas tensions, response to changes in the composition of ambient air. Pediatr Res 1973;7:174-183. 20. Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life. Ill. Incidence of apnea and periodic breathing. Pediatrics 1977;60:4J 8-425. 21. R~chards JM, Alexander JR, Shinebourne EA, de Swiet M, Wilson A J, Southall DP. Sequential 22 hour profiles of breathing patterns and heart rate in 110 full-term infants during their first 6 months of life. Pediatrics 1984;74:763777. 22. Shivapuri CR, Martin R J, Carlo WA, Fanaroff AA. Decreased ventilation in preterm infants during oral feeding. J PED~Aa'R 1983;!03:285-289. 23. Matthew OP, Clark ML, Pronske ML, Luna-Solarzano HG, Peterson MD. Breathing pattern and ventilation during oral feeding in term newborn infants. J PEDIA'rR 1985;106:810813. 24. Blanco CE, Dawes GS, Hanson MA, MczCooke HB. The resl~onse to hypoxia of arterial chemoreceptors in fetal sheep and newborn lambs. J PhysioI (Lond) 1984;351:25-37. 25. Gurwitz D, Spriet LL, Bryan MH, Bryan AC. Carotid body function in siblings of S1DS [abstract]. Pediatr Res I980;14:643.