• No results found

Apneic Spells and Sleep States in Preterm Infants

N/A
N/A
Protected

Academic year: 2020

Share "Apneic Spells and Sleep States in Preterm Infants"

Copied!
8
0
0

Loading.... (view fulltext now)

Full text

(1)

Apneic

Spells

and Sleep

States

in Preterm

Infants

M. Gabriel, M.D., M. Albani, M.D., and F. J. Schulte, M.D.

From the Department of Pediatrics, University of Gottingen, GOttingeti. West Geniiani,

ABSTRACT. The incidence of apneic spells during different

sleep states, active sleep, quiet sleep, and undifferentiated

sleep was determined in eight preterm infants of 30 to 35

weeks’ conceptional age, by means of a polygraphic

recording technique. They were free of perinatal and

post-natal complications other than apnea. During their active or

rapid eye movement (REM) sleep they showed significantly

more apneic episodes which were also longer lasting and

they were accompanied by bradycardia of a greater severity.

The organization of the immature nervous system with a

preponderance of inhibitory synaptic connections and the

additional inhibition of spinal motoneurons during REM

sleep are likely to be the cause of apneic spells in otherwise

“normal” preterm infants. Pediatrics, 57:142-147, 1976,

NEONATE, APNEA, RESPIRATION, SLEEP.

Bryan and Bryan’ recently described thoracic wall instability in newborn infants during active or rapid eye movement (REM) sleep. In 86% of

preterm infants of less than 37 weeks’

conception-al age Fenner et a!.2 observed periodic breathing

which occurred most frequently while the babies

were in REM sleep. Daily et al.3 found apneic

spells occurring when respiration was periodic,

from which one can assume that the infants were in active sleep.

There is ample evidence from both animal experiments’ and studies in human infants5 that spinal motoneurons are subjected to strong descending inhibitory influences during active sleep. If-as is to be expected-respiratory moto-neurons are included in this inhibition, the main-tenance of regular respiration must be more

difficult during active than during quiet sleep. As

preterm babies spend a much longer time asleep and a much higher percentage of this time in active or HEM sleep than older infants,67 REM

sleep inhibitory mechanisms on respiratory

motoneurons may play an important role in the

preterm baby’s difficulties in breathing.

Thus, in this study the distribution of 493

apneic spells between active or REM and quiet or non-REM sleep was investigated in eight infants

by means of a polygraphic monitoring

tech-nique.

METHODS

Subjects

Eight preterm infants of a gestational age range of 28 to 34 weeks and birthweights between 990 and 2,100 gm were investigated at a conceptional age (gestational age plus age from birth) of 31 to 35 weeks (Fig. 1) with postnatal age varying between 2 and 48 days. The gestational age was calculated from the first day of the mother’s last

menstrual period until birth. Infants were

included in this study only when their mothers were certain about their last menses and when the

Dubowitz et a!.’ score revealed a similar

conceptional age estimate. The infants were care-fully selected on the basis that the pregnancy, birth, and postnatal period were uneventful, except for the premature delivery. Only one infant had a bilirubin level of 14.4 mg/100 ml, probably due to heavy bruising of the lower extremities during delivery; in this instance an exchange transfusion was performed. Neurolog-ical and physical examinations in the postnatal period and at the time of discharge were appro-pnate for conceptional age. On each baby one to four polygraphic recordings were performed with a total of 19 investigations.

Recording Technique

A polygraphic sleep recording of two to four

(Received March 26; revision accepted for publication June

5, 1975.)

Supported by grant SFB 33 from the Deutsche

Forschungs-gemeinschatt.

ADDRESS FOR REPRINTS: (MG.)

(2)

weeks

I

asP.

28 29 30 31 32 33 34

S I I I

-n

.

..

I-

#{149}

F

.

39

69

62

-. 53

101

-. 99

26

F

#{149}

44

FIG. 1. Gestational age and age at time of recording (closed circles). a.sp. = total of apneic

spells recorded for each preterm infant.

hours in duration was obtained from each baby lasting for about two interfeeding intervals.

During the recording the infants were kept under

the usual incubator conditions at neutral

temper-ature and breathing room air. Polygraphic

record-ings were done on an eight-channel Schwartzer EEG machine and consisted of (1) respiration,

registered by a thermistor attached to the infant’s

nose and, additionally, by carbon dioxide

estima-tion via a tube in the epipharyngeal space; (2)

heart rate, recorded by conventional

electrocar-diogram; (3) facial and body activity, contin-uously observed during the recording and

mdi-cated by a code on the paper write-out; (4)

observed rapid eye movements, registered by a

push-button device; (5) EEG, recorded with

silver/silver-chloride stick-on electrodes in a

montage of four bipolar leads from bilateral

frontocentral and frontotemporal regions. The

electrode resistance was about 4 to 5 kohms; time

constant, 0.3 second with a high frequency filter

at 70 c/sec.

Visual Analysis of Polygraphic Recordings

All records were visually analyzed

page-by-page (20-second epoch):

Respiration-Respiration was counted and the

ratio of the longest/shortest breath-to-breath

interval was calculated for each 20-second epoch

as an indicator of respiratory regularity. Pauses of

more than ten seconds were coded as apnea. Most

of the apneic spells ceased spontaneously and

some were terminated by manual stimulation;

none of them required artificial ventilation.

Heart Rate-Preceding each apneic episode,

the heart rate was calculated and a decrease of at

least 10% during the apneic episode was indicated as cardiac slowing; a heart rate of below 100 beats per minute was coded as bradycardia.

EEG-The maturational changes in EEC

patterns during sleep in preterm infants were first described by Dreyfus-Brisac.’ According to a

special EEC pattern coding system, introduced

by Parmelee et aL” and extended by Schulte et

steep state mm S 0 /. S 0

AS

Q

S

UDS

138 ± 41

37 14

30 ± 7

65 8

18 ± 4

15 8

FIG. 2. Mean and SD (minutes and percentage) for each active or REM sleep (AS), quiet sleep

(QS), and undifferentiated sleep (UDS) calculated from 19 polygraphic recordings of eight

preterm infants.

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(3)

x x

. .

x x

x .

x x

x S

80 AS

x

60

40

20

s/S

ioo

80

QS

60

40

20

S/. 100

80

UDS

60

40

S x #{149}

20 ,#{248}x:x:.:.xxe:x: f

record - number

FIG. 3. The distribution of apneic episodes of more than ten seconds in duration during AS, QS,

and UDS. The percentage of total sleep time (X) is compared with the percentage of apneic

episodes (closed circles) occurring during a given sleep state. Individual figures are given for each

of the 19 recordings as well as for the mean and SD calculated from all recordings.

S = significant at the P < .001 level.

0/0 100 . .

.

. .

. o T S.

, x x X

x x

x

xXXXIXI:X

I

.-,---. ...#{149}.

-

_._., . . ..,‘. 1#{149}1 i.i#{149}.

a!.,” the EEC pattern predominant within each 20-second epoch was identified. Thus, we were able to recognize special EEC patterns indicative for active or REM sleep and others indicative for quiet or non-REM sleep.

Definition of Sleep States

Three subsequent 20-second epochs were combined for the identification of sleep states, which were defined as follows:

Quiet Sleep-Paroxystic EEG with long-lasting

bioelectric blackouts without any rapid eye movements.

Active Sleep-Non-paroxystic although fre-quently discontinuous EEC with rapid eye move-ments and/or body movements.

Every one-minute sleep-epoch which could not thus be identified as either active or quiet sleep was classified as undifferentiated sleep.

RESULTS

Nineteen polygraphic investigations of eight

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(4)

sleep

state

actual

- ratio ofa.sp.

estimated records (n)

AS

Q

S

UDS

129 ± 0.17 S. 0.

0.42

0.22

S. 0.

1.03 0.46 S. 0.

19

11

15

FIG. 4. In 19 recordings of eight preterm infants during AS an excess of 29% apneic spells (asp.)

occurred in respect to what was estimated from the AS proportion of total sleep time. During QS

in eight recordings, no apneic spells were observed. In the remaining 1 1 recordings only 42% of

the apneic spells were encountered from what was estimated on the basis of QS proportion of

total sleep time. During UDS the actual incidence and the estimate of apneic spells was almost

identical.

infants gave a total of 3,971 minutes of recording

time with 209 ± 53 minutes per record.

Sixty-five percent of the time was spent in clearcut

active or REM sleep, 18% in quiet sleep, and 15%

in imdifferentiated sleep (Fig. 2). Regularity of

respiration indicated by the longest/shortest

breath-to-breath interval ratio was significantly

greater in quiet sleep than in active sleep with

ratios of 2.29 ± 2.01 and 4.48 ± 3.09

respective-ly.

A total of 493 apneic spells were recorded, with

a mean of 26 per record and a range between 6

and 76. The duration of the apnea varied from 10

to more than 60 seconds with cardiac slowing in

65%. Only in two recordings of two different infants, both older than four weeks postnatal age, did all the apneic spells last less than 20 seconds. Cardiac slowing occurred in 198 out of the 370 short apneic spells with a duration of 10 to 20 seconds and in 51 of these apneic episodes heart rate fell below 100 beats per minute.

Seventy-nine percent of the 493 apneic spells occurred during active sleep (65% of total sleep time), only 6% during quiet sleep (18% of total sleep time), and 15% during undifferentiated sleep (15% of total sleep time) (Fig. 3). A signifi-cant excess of 29% ± 17% more apneic spells occurred during active sleep than was to be

sleep

state

apnoeic

spe

I Is

(n)

totaL

with

with

cardiac slowing bradycardia

AS

Q S

UDS

390

29

74

252

15

41.

103

(61)

4 (27)

16

FIG. 5. Number of apneic spells with cardiac slowing (decrease in heart rate of more than 10%)

and with bradycardia (heart rate below 100 beats/mm) in respect to different sleep states.

Numbers in parentheses = bradycardia/cardiac slowing X 100.

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(5)

Sleep

state

apnoeic

spells(n)

total <2Osec 20-39sec 4Osec

AS

QS

UDS

390

29

74

294

25

51

74

4

13

22

-10

FIG. 6. Number of apneic spells of different durations in respect to different sleep states.

expected from the active/total sleep ratio. Very few apneic spells occurred during quiet sleep. In eight recordings from four infants no apneic spells

were encountered during well-defined quiet sleep

states. In the remaining 1 1 recordings the

mci-dence of apneic episodes during quiet sleep reached only 42% ± 22% of what was expected from the quiet/total sleep ratio. The appearance of apneic spells during undifferentiated sleep showed no significant deviation from the expected value, although four recordings did not

show any episodes in undifferentiated sleep (Fig.

4).

Cardiac slowing was more frequently observed with apneic spells during active sleep (65%) than during quiet sleep (52%). Furthermore, during active sleep in 41% of the apneic spells with cardiac slowing, pronounced bradycardia (heart rate below 100 beats per minute) occurred in comparison with only 27% during quiet sleep (Fig. 5).

Apneic spells of longer than 20 seconds in duration tended to be less frequent in quiet sleep than in other sleep states; the difference, however, was not significant. None of the 32 apneic spells lasting more than 40 seconds occurred during quiet sleep (Fig. 6).

DISCUSSION

Sleep States

The exact definition of sleep states in very immature preterm infants is rather difficult, for, in contrast to older infants and adults, differences in the EEC patterns are less striking, rapid eye movements under closed lids are often easily

missed, small body movements occur in both

sleep states, tonic chin muscle activity cannot

always be encountered during quiet sleep, and

respiration may remain irregular even when all

other parameters are indicative of quiet sleep.’2 We, therefore, defined sleep states according to two parameters which are the most reliable in this age group, i.e., EEC and eye movements.

Regu-larity of respiration, although not used as a

parameter for the definition of sleep in this study, was nevertheless well in agreement with the identification of either well-defined active sleep or quiet sleep. Furthermore, the distribution of sleep states found in this study is similar to that reported in the literature.7

Apneic Spells

The frequency of apneic spells in preterm infants depends on how they are defined. It is noteworthy that apnea of more than 10 seconds in duration occurred in each of our eight infants and many times in each of our 19 polygraphic record-ings. The incidence of such apneic spells has not yet been reported for otherwise “normal” infants of 30 to 35 week’s conceptional age. In Daily et

al.’s study,’ six out of 12 low-birthweight infants without other perinatal or postnatal complica-tions had apneic spells of more than 20 seconds in duration. Our method of long polygraphic

mom-toring appears to reveal more apneic episodes than previously reported, even if we only rely on those longer than 20 seconds.

Since pronounced bradycardia does occur in apneic spells of 10 to 20 seconds in duration, we included all apneic episodes longer than ten seconds. Respiratory pauses of less than ten seconds in duration are usually thought to be of no pathological significance as they are not connected with bradycardia.2-

REM Sleep and Apnea

(6)

more often, they are more frequently connected

with cardiac slowing and severe bradycardia, and

they tend to be longer lasting during active than quiet sleep. These findings can be explained by

the well-known inhibitory influences acting on

spinal motoneurons and primary afferents during

active or REM Whereas during active

sleep small and insignificant muscle twitchings

frequently occur as an expression of the brain

stem noise,’’ all major motor activity is success-fully inhibited. This inhibition, in all groups,

interferes with proprioceptive reflex control of

intercostal muscles and probably with other affer-ents involved in regulating ventilation and,

there-fore, with respiration which becomes irregular

with short pauses.

COMMENT

In the premature baby the inhibition of

respi-ratory motoneurons during REM sleep becomes

particularly effective for two reasons: (1) The

more immature the infant the more time it spends

in active sleep and only few epochs can be

regarded as clearcut quiet sleep. From 32 weeks’

conceptional age to three months after term, the

percentage of quiet sleep increases from about

20% to about 60% of total sleep time.’-

Further-more, during the same maturational period total

sleep time decreases from over 18 to about 14

hours per day. Thus, the time the baby is obliged

to overcome REM sleep inhibition of spinal

respiratory motoneurons becomes much less with

increasing age and maturity. (2) One of the most

important morphological features of central nervous system immaturity is the lack of dendritic arborization and axodendritic synaptic

connec-tions.’5 Thus, we have to assume that synaptic

excitatory drive on respiratory neurons in both brain stem and spinal cord is much weaker in preterni than in term infants. Furthermore,

axoso-matic synaptic connections tend to be more

inhibitory than excitatory and thus exhibit a powerful control of neuronal cell activity.’ In preterm infants, this inhibition is enhanced because of the small overall synaptic connections due to minor arborization.

As a result of these morphological events

during maturation, it is difficult for the preterm infant to maintain a strong excitation of

respira-tory neurons over a long time or with a regular

recurrence rate.

The rhythmic excitation of respiratory neurons, the maintenance of this excitation over a certain period of time to allow a full inspiration, and finally the synchronization of a large motoneuron

pool to guarantee strong muscle power have to

counteract inhibitory mechanisms, which are the

stronger the more immature the infant is. For

reasons based on both structure and function of

the normal but immature brain, it is

understand-able that even without additional risk factors the preterm infant often fails to breath and that it

fails more frequently in active or REM rather

than in quiet sleep.

REFERENCES

1. Bryan AC, Bryan MH: Respiratory control in newborn

infants. Read before the Congress for Perinatal

Medicine, Berlin, 1974.

2. Fenner A, Schalk U, Hoenicke H, ci’ at: Periodic

breathing in prelnattire and neonatal babies:

mci-dence, breathing pattern, respiratory gas tensions,

response to changes in the composition of ambient

air. Pediatr Res 7: 174, 1973.

3. Daily WIR, Klaus M, Meyer HBP: Apnea in premature

infants: Monitoring, incidence, heart rate changes,

and an effect of environmental temperature.

Pediat-rics 43:510, 1969.

4. Pompeiano 0: Muscular afferents and motor control

during sleep. In, Granit R (ed):Muscular Afferents

and Motor Control. Stockholm, Almquist &

\Viksell, 1966, l 415.

5. Prechtl HFR, Viach V, Lenard HG, Kerr-Grant 1):

Exteroceptive and tendon reflex in various

behav-ioral states in the newborn infant. Biol Neonat

11:159, 1967.

6. Roffwarg HP, Mnzio IN, Dement WC: Ontogenetic

development of the human sleep-dream cycle.

Science 152:604, 1966.

7. Parmelee All, Wenner Wil, Akiyama Y, ci’ at: Sleep

states in prelnature infants. Dev Med Child Neurol

9:70, 1967.

8. Dubowitz LMS, Dubowitz V, Goldberg C: Clinical

assessment of gestational age in the newborn infant.

J Pediatr 77:1, 1970.

9. Dreyfus-Brisac C: The electroencephalogram of the

premature infant. World Neurol 3:5, 1962.

10. Parmelee AH, Schulte FJ, Akiyama Y, et at: Maturation

of EEG activity during sleep in premature infants.

Electroencephalogr Clin Neurophysiol 24:319, 1968.

11. Schulte FJ, Michaelis R, Nolte R, et at: Brain and

behavioural maturation in newborn infants of

diabetic mothers: I. Nerve conduction and EEG

patterns. Neuropaediatrie I :24, 1969.

12. Dreyfus-Brisac C: Ontogenesis of sleep in human

prenia-ture after 32 weeks of conceptional age. Dcv

Psychobiol 3:91, 1970.

13. Avery ME: The lung and its disorders in the newl)orn

infant. In, Major Problems in Clinical Pediatrics, ed

3. Philadelphia, WB Saunders Co, 1974, vol 1.

14. Prechtl HFR, Lenard HG: A study of eye movements in

sleeping newborn infants. Brain Res 5:477, 1967.

15. Purpura DP, Schade IP: Growth and maturation of the

brain. In, Progress in Brain Research. Amsterdam,

Elsevier Publishing Go, 1964, vol 4.

16. Eccles IC: The Inhibitory Pathways of the Central

Nervous System. Liverpool, Liverpool University

Press, 1969, pp 101-104.

ACKNOWLEDGMENT

We wish to thank Miss L. Michaelis, Mr. P. Patzig, and

Mr. H. %Vulbrand, without whose skillful technical assistance

this study could not have been completed.

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(7)

1976;57;142

Pediatrics

M. Gabriel, M. Albani and F. J. Schulte

Apneic Spells and Sleep States in Preterm Infants

Services

Updated Information &

http://pediatrics.aappublications.org/content/57/1/142

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

Information about ordering reprints can be found online:

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(8)

1976;57;142

Pediatrics

M. Gabriel, M. Albani and F. J. Schulte

Apneic Spells and Sleep States in Preterm Infants

http://pediatrics.aappublications.org/content/57/1/142

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1976 by the

been published continuously since 1948. Pediatrics is owned, published, and trademarked by the

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

References

Related documents

That’s why it is used in various drug delivery systems like drug targeting, controlled release and permeation enhancement of drugs 9.. Disadvantages

It has been shown that after the experimental animals were injected with the cerebrospinal fluid irradiated with ultraviolet radiation in the area of biologically-active

There were specified the differences in the behavior of individual lanthanides in REE composition of formations and their factions - the acid extract (1.8% HCl), taken as a

scheme based on traditional encryption scheme with increase in algorithm rounds to encrypt the digital image but these schemes are not appropriate for encrypting the DICOM

Wireless Sensor Network (WSN) is a dense network consisting of little and light-weight nodes, which are broadcasted over the system in giant numbers by the

A user can fire Tiny-SQL queries (similar to SQL queries) to the base station. These queries are distributed to all the relevant nodes in the WSN from the base station that

The review carried out in the present article, evidences the validity of the use of the TPSR model as an intervention programme with children and young people through physical

Basic components of the new generation R744 VAC system of the bus are numbered between 1 to 6 in Fig. The working principle of the R744 VAC system based on the refrigerant’s