Europ. J. Pediat. 122, 257--261 (1976) 9 by Springer-Verlag 1976

Cardiac Showing and Respiratory Arrest in Preterm Infants* M. Gabriel a n d M. A l b a n i Department of Pediatrics II, University of G6ttingen, G6ttingen I~eeeived March 22, 1976

Abstract. Changes in respiration and heart rate during sleep states have been recorded by a polygraphic device in healthy preterm infants. Cardiac slowing/bradycardia often coincide with respiratory arrest/apnea. Bradycardia starts early during apneic spells. The incidence of respiratory arrest and cardiac slowing and their simultaneous occurrence is significantly increased by the active or REM sleep state. The physiologic, inhibitory mechanisms of active sleep suggest a neurogenic etiology of episodes of cardiac slowing/bradycardia and/or respiratory arrest/apnea in prematures. Key words: Preterm infants - - Bradyeardia - - Apneic spells - - Active sleep - - Neuronal inhibition. L o n g - t e r m electrocardiographic m o n i t o r i n g has shown a high incidence of s p o n t a n e o u s b r a d y c a r d i a in p r e t e r m i n f a n t s [8, 11 ]. B r a d y c a r d i a also occurs d u r i n g long lasting apneas [2], b u t even brief apneic spells often show m a r k e d cardiac slowing [4]. The close correlation of a p n e a to the state of active or g E M (rapid eye m o v e m e n t ) sleep seems to be i n d i c a t i v e t h a t n e u r o n a l i n h i b i t o r y m e c h a n i s m s m a y p l a y a n i m p o r t a n t role i n the etiology of apneie spells [4]. I t was the purpose of this s t u d y to investigate the coincidence of cardiac slowing a n d r e s p i r a t o r y arrests as well as their d i s t r i b u t i o n w i t h i n the sleep states, a s s u m i n g a c o m m o n n e u r a l i n h i b i t o r y influence on respiration a n d h e a r t rate in the i m m a t u r e subject.

Methods

Subjects Eight preterm but otherwise healthy infants of a gestational age range of 28--34 weeks and birth weights of between 990--2100 g were investigated at a conceptional age (gestational age plus age from birth) of 3i 35 weeks. Neurologic and physical examinations in the postnatal period and at the time of discharge were normal and ~ppropriate for conceptional age. On each baby 1--4 polygraphic recordings were performed with a total of 19 investigations.

Recording Technique and Analysis I~ecording technique of EEG, EKG, respiration, eye and body movements and their analysis were identical as in our previous investigation [4]. Brief comments should therefore be sufficient. Heart rate: Heart rate was counted and a decrease of at least 10% was indicated as cardiac slowing; a heart rate of below 100/rain was coded as bradycardia. The total amount of cardiac slowing, however, includes all the observed bradycardias. * Supported by the Deutsche Forsehungsgemeinschaft SFB 33.

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M. Gabriel and M. Albani

Respiration: Pauses of more than 3 s duration were defined as respiratory arrests and differentiated as apneic spells (respiratory arrest of more than 10 s duration), pauses of periodic breathing [3], and nonperiodic pauses. Nonperiodic pauses were considered only when coinciding with cardiac slowing. Results

A total of 4000 rain of sleep were analyzed from 19 recordings of 8 infants. Seven hundred and seventy-eight episodes of cardiac slowing, 493 apneic spells, and 2450 respiratory pauses of periodic breathing were counted. These events were found in each single record.

1. Cardiac Slowing and Bradycardia Seventy-three percent of episodes of cardiac slowing coincided with respiratory arrest of at least 3 s duration presenting either apneic spells or periodic or nonperiodic pauses. Regarding bradycardia alone, 850//0 of this severe cardiac slowing coincided with respiratory arrests (Table 1). The decrease in heart rate was more severe when episodes of cardiac slowing were connected with respiratory arrests. The incidence of bradyeardia, defined as a heart rate below 100 beats/rain, was 30% in episodes of cardiac slowing connected with respiratory pauses (170 out of 564), but only 14% in such episodes without obvious changes in the respiratory pattern (31 out of 214) (Table 1). Analogous to the fact t h a t we found bradycardia during respiratory arrests of less than 10 s duration, 68~o of bradycardia occurring during apneic spells showed an early onset with the initial 10% reduction of heart rate less t h a n 9 s after respiration ceased. I n all cases of early bradycardia during apneic spells, heart rate and respiration were reestablished rather simultaneously. Eighty-one percent of the episodes with cardiac slowing including bradycardia occurred during active or R E M sleep, although t h a t sleep state represented only 65% of total sleep time. Active sleep revealed a higher incidence of decrease in heart rate, especially for bradycardia, combined with a respiratory arrest than Table 1. Incidence of cardiac slowing/bradycardia in relation to simultaneous respiratory arrest. Percentage of respiratory subgroups is based on all coinciding events as 100%

cardiac slowing n = 778

bradycardia n -- 2 0 1

without respirat, changes

27 % n=21~

15 % .:31

coinciding respirat, arrest

73 =/= n=56~

85 % ~17o

as n o n . periodic periodic opneo

12%

21%

33%

9%

55%

70 %

Neurogenic Apnea and Bradycardia

259

Table 2. Incidence of several parameters in state of active or REM sleep

total

% active

n

/.000 min

sleep cardiac slowi ng

778

in sleep

65

81

without respirat, changes

214

75

coinciding respirat, arrest

564

83

201

bradycardia

78

without respiraf, changes

31

42

coinciding respirat, arrest

170

84

respiratory

arrest as p e r i o d i c b r e a t h i n g as apnoea

2~50 ~93

85 81

Table 3. Occurrence of cardiac slowing/bradyeardia during apneic spells of various duration. In right column, the ratio of early-to-late onset of bradycardia is related to increasing duration of apneas

apnoeic spells and cardiac duration of apnoeic spells [sec]

w i t h cardiac

slowing

O/o

slowing

with bradycardia HF l,O

91

86

1.2

< 20

,:370

n~

for cardiac slowing without any change of respiratory pattern (Table 2). Thus, 96% of all periodic respiratory pauses combined with a decrease in heart rate were observed while the infant was in active sleep.

260

M. Gabriel and M. Albani

2. Respiratory Pauses and A pneic Spells The well-known irregularity of respiration during active sleep [9] revealed many nonperiodic, but distinct pauses of more than 3 s duration; however, periodic breathing (85%) and apneas (81%) also occurred predominantly in active sleep (Table 2). Twenty-five percent of apneas started from periodic breathing, 20% with or immediately after rapid eye movements. In the group of respiratory pauses lasting less than 10 s there was no correlation between the duration of the respiratory arrest and the incidence of bradycardia. In apneic spells, however, the incidence of cardiac slowing as well as the percentage of bradycardia increased with longer duration of apneas (Table 3). In spite of the overall high percentage of early onset bradycardia in episodes of respiratory arrest the incidence of bradycardia with late onset increased with the duration of apneie spells (Table 3). Sometimes, both early and late bradyeardia was observed during the same apnea, when early bradycardia was followed by a further decrease in heart rate, while we never saw an initial increase of heart rate during apneie spells. Discussion

A long-term electrocardiographic monitoring of preterm infants reveals a high incidence of cardiac arrythmias [8, it]. During prolonged apneic spells bradycardia is often seen appearing about 15 s after apneic spells started [2, 5, ]1]. Although some decreases in heart rate have been described during respiratory arrests of periodic breathing [5], we found one third of cardiac slowing combined with periodic breathing sometimes even showing bradycardia, ttypoxia as well as "immaturity of the autonomic nervous system" [1, 7, 11] has .been suggested as causing bradycardia in preterm infants. Based on neurophysiologic aspects, however, our results might be indicative of another mechanism : Apneic spells occur predominantly during active sleep [4]. Additionally, other parameters, like short respiratory arrests or spontaneous cardiac slowing, or a combination of both, were found to occur also preferentially during active sleep. Therefore we suggest similar mechanisms as we discussed for the etiology of apneic spells [4]: Besides the linkage of cardiovascular and respiratory "centers" in the brain stem, there is evidence from animal studies, that the inhibitory system descending to preganglionic sympathetic neurones belongs to the descending reticulospinal system which exhibits a strong inhibitory influence on spinal motor reflex path~ way [6, 10]. Therefore the combination of cardiac slowing and respiratory arrests during active sleep may occur because the high activity of this reticulospinal system during active sleep also acts on the spinal sympathetic output. The inhibition of spinal motor reflex pathways causes a respiratory arrest, the decreased sympathetic output reveals cardiac slowing. Since we never saw an increase of heart rate during respiratory arrest, as expected due to the hypoxic response, as well as bradycardia starts early in apnea, only the late bradycardia of long-lasting apneas seems to be caused by hypoxia and hypercapnia. The high percentage of brief respiratory arrests combined with cardiac slowing or even bradycardia during active sleep suggests rather a common central nervous mechanism based

Neurogenic Apnea and Bradycardia

26i

on physiologic properties in a h e a l t h y b u t i m m a t u r e central n e r v o u s system (see also [4]).

Aclcnowledgement. We wish to thank Mr. P. Patzig and Mr. H. Wulbrand for their skilful technical assistance.

References 1. Church, S. C., Morgan, B.C., Oliver, Th. K., Guntheroth, W.G.: Cardiac arrhythmias in premature infants: an indication of autonomic immaturity ? J. Pediat. 71, 542--546 (1967) 2. Daily, W. I. P~., Klaus, M., Meyer, H. B. P.: Apnea in premature infants: monitoring, incidence, heart rate changes, and an effect of environmental temperature. Pediatrics 43, 510--518 (1969) 3. Fenner, A., Schalk, U., t{oenicke, H., Wendenburg, A., l~oehling, T. : Periodic breathing in premature and neonatal babies: incidence, breathing pattern, respiratory gas tensions, response to changes in the composition of ambient air. Pediat. Res. 7, 174--183 (1973) 4. Gabriel, M., Albani, M., Schulte, F. J. : Apnoeic spells and sleep states in preterm infants. Pediatrics 57, 142--147 (1976) 5. Girling, D. J. : Changes in heart rate, blood pressure and pulse pressure during apnoeic attacks in newborn babies. Arch. Dis. Childh. 47, 405--409 (1972) 6. Illert, M., Gabriel, M.: Descending pathways in the cervical cord of cats affecting blood pressure and sympathetic activity. Pfliigers Arch. 83~, 109--124 (1972) 7. Lipton, E.L., Steinschneider, A., Richmond, J. B.: The autonomic nervous system in early life. New Engl. J. Med. 273, 147--153 (1965) 8. Morgan, B. C., Bloom, R. S., Guntheroth, W. G. : Cardiac arrythmias in premature infants. Pediatrics 115, 658 661 (/965) 9. Parmelee, A.H., Wenner, W. H., Akiyama, Y., Schultz, M., Stern, E.: Sleep states in premature infants. Develop. med. Child. Neurol. 9, 70--77 (1967) 10. Pompeiano, 0.: Muscular afferents and motor control during sleep. In: Muscular afferents and motor e}mtrol, Nobel Symposium I ED: R. Granit, pp. 415 436. Stockholm: Almquist & Wiskell, 1966 11. VglimS~ki,J., Tarlo, P.A.: Heart rate patterns and apnea in newborn infants. Amer. J. Obstet. Gynec. 116, 343--349 (1971) Dr. M. Gabriel UniversitS~ts-Kinderklinik NeuropSAiatrische Abteilung Humboldtallee 38 D-3400 GSttingen Federal Republic of Germany

Cardiac slowing and respiratory arrest in preterm infants.

Europ. J. Pediat. 122, 257--261 (1976) 9 by Springer-Verlag 1976 Cardiac Showing and Respiratory Arrest in Preterm Infants* M. Gabriel a n d M. A l b...
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