Cardiac slowing and respiratory arrest in preterm infants

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.Supported by the Deutsche Forschungsgemeinschaft SFB 33.     

Rapid eye movement sleep, motoneurone inhibition, and apneic spells in preterm infants.

Not principally different from the results obtained in more mature subjects, monosynaptic reflex excitability of spinal motoneurones in preterm infants decreases during active sleep. However, in preterm infants the electric reflex response is not abolished, and is not even continuously depressed during the entire active sleep period. Spinal motoneurone inhibition is demonstrable only during certain periods of active sleep, and it is during this state of decreased spinal motoneurone excitability when apneic spells predominantly occur.     

Sleep induced PO2-changes in preterm infants

In seven healthy preterm infants the transcutaneous PO₂ was measured during different sleep states. The tcPO₂ is lower during active sleep than during quiet sleep and shows a higher variability in active sleep. The incidence of apneic spells, which occur predominantly during active sleep, was not found to be correlated to tcPO₂ levels.Supported by the Deutsche Forschungsgemeinschaft, SFB 33This is a part of the thesis     

Infant sleep apnea profile: preterm vs. term infants

By means of polygraphic sleep recording, the sleep apnea profile with respect to the number and duration of inactive, obstructive and mixed apneic episodes as well as periodic breathing has been investigated in infants born preterm at 40, 52 and 64 weeks conceptional age and compared to that of term infants. At 40 weeks preterm infants showed significantly more apnea and periodic breathing compared to term infants. The difference was essentially due to obstructive and mixed apnea in non-REM sleep.There was a sharp decrease in all apneic variables—inactive, obstructive and mixed apnea as well as of periodic breathing—at 52 weeks conceptional age in infants that were previously preterm. Both groups exhibited a rather identical sleep apnea profile at 64 weeks. Two prospectively studied infants in the preterm group later became SIDS victims. One of them might have been identified as being at risk on the basis of his apnea profile compared to the normative data now available.Abbreviations REM rapid eye movements     

REM sleep prevents sudden infant death syndrome

Near-miss events were observed to occur in indeterminate sleep in a preterm infant reaching term at 6 weeks after birth. Moreover, prolonged sleep apnea and periodic respiration were frequently encountered in non-REM sleep. In view of the observation that pathologic sleep apnea occurs in non-REM sleep and the apparently contradictory findings of respiratory depression and more frequent apneas during REM sleep, apneic episodes during REM sleep were analysed in relation to phasic REM events. The frequent occurrence of respiratory pauses in REM burst-free periods of REM sleep suggests that tonic REM mechanisms inhibit respiratory neurons, while phasic REM mechanisms are facilitatory and protect an infant from prolonged sleep apnea.     

Esophageal function of infants with sudden infant death--risk

In 24 patients at risk for SIDS (12 infants with a near miss event and 12 infants with apnea and perioral cyanosis during sleep) respiratory and esophageal function were investigated by impedance pneumography (IP) and esophageal manometry combined with simultaneous pH-monitoring (EMPH). Both groups had ad early pathologic breathing pattern, but did not show any difference in the recorded parameters (number of apneic spells, longest apneic spell, apneic spells longer than 10 seconds, transcutaneous oxygen pressure, mean apnea time). Near miss infants had about 50% more manometric refluxes (15.4 +/- 1.3) than the apnea/cyanosis group (9.9 +/- 2.2). This difference was mainly caused by a significant rise of reflux episodes without pH-change (near miss 8.5 +/- 3.1 versus 2.9 +/- 1.4 in apnea/cyanosis infants). Furthermore, propulsive peristaltic properties after induced swallows were more disturbed in the near miss group (3.3 +/- 1.0 versus 6.1 +/- 1.9). On the other hand, the apnea cyanosis group showed significantly more pH-drops under 4 (6.8 +/- 2.3 vs 2.4 +/- 0.7), which might be due to a more rapid clearance of neutralising milk from the stomach in these infants. In conclusion the study showed that infants with a near miss event in the anamnesis suffer from a more pathologic esophageal motor function when compared with infants with apneic spells and cyanosis during sleep. Near miss infants are also considered to have a delay of gastric clearance.     

Skin blood flow changes during apneic spells in preterm infants

Changes in skin blood flow during apneic spells were determined in 18 preterm infants using a diode laser Doppler flow meter without light conducting fibres. Heart rate, nasal air flow, impedance pneumography, skin and incubator temperature and laser Doppler skin blood flow were recorded simultaneously in each infant. During 212 apneic spells with a duration of 11.6 ± 7.5 s (mean ± S.D.) (range 6.0–48.0 s), the laser Doppler skin blood flow was measured. In all children except one, the majority of the apneic spells was associated with a decrease in skin blood flow. During 155 apneic spells (73%) skin blood flow decreased significantly P < 0.025), the maximum decrease being 16.7 ± 14.8%, 28.5 ± 23.9% and 18.9 ± 16.1% (mean ± S.D.) for central, obstructive and mixed apneic spells, respectively. The decrease in skin blood flow started immediately after the beginning of apneic spells in 71%, the rest started with a mean delay of 3.4 s (range 0.1–7.0 s). No relation was found between the decrease in skin blood flow and the duration of the apneic spells. Thirty-four percent of the apneic spells were accompanied by bradycardia. In apneic spells accompanied by bradycardia the decrease in skin blood flow was not related to the fall in heart rate.     

Relationship between functional residual capacity and oxygen desaturation during short central apneic events during sleep in "late preterm" infants

Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O(2)-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O(2)-desaturation during short central apneic events (>3 s) in "late-preterm" infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 +/- 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O(2)-desaturation (drop in SpO(2) >5% from the baseline, lowest SpO(2) during apnea: 91.4 +/- 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O(2)-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.     

Central hypoventilation during quiet sleep in two infants.

Expired ventilation (VE), tidal volume (VT), frequency (f), and alveolar PCO2 (PACO2) were examined in six normal infants at 41 to 52 weeks post-conceptional age and in two infants who were apneic at birth. Their response to breathing 5% carbon dioxide in air and to 100% oxygen in quiet sleep were compared to those in rapid eye movement (REM) sleep. VE in normal infants was 259 ml/kg/min in REM and 200.2 ml/kg/min in quiet sleep with the difference being due to decreased carbon dioxide production and to decreased dead space. VE increased 34.4 ml/kg/min/mm Hg of PCO2 elevation with 5% carbon dioxide breathing during REM and was not significantly different during quiet sleep. During oxygen breathing VE fell by 32.7% at 30 seconds before increasing again. In the affected infants, VE and PACO2 during REM at 1 and 4 months were normal. At 1 month, during quiet sleep, each infant became apneic and PACO2 rose 9 and 8 mm Hg/min respectively. At this time mechanical ventilation was begun. At 4 months, during quiet sleep, VE was 0.064 and 0.063 ml/kg/min at PACO2 of 66 mm Hg in each infant. The change was due entirely to a decrease in VT to 2.3 and 2.5 ml/kg. At this time 5% carbon dioxide breathing given during normal ventilation in REM produced an abrupt fall in VT to 2.0 and 2.2 ml/kg with no change in frequency. Oxygen breathing during REM at one month had no effect but at 4 months produced apnea requiring mechanical ventilation after one minute. The findings suggest that the ventilatory response to carbon dioxide is (1) important in initiation of extrauterine ventilation and (2) in sustaining ventilation particularly in quiet sleep. It is not necessary in sustaining ventilation awake or in REM sleep and it represents a balance between the stimulatory and depressant effects of carbon dioxide on the central nervous system.     

Apnea associated with regurgitation in infants

To determine whether regurgitation might be a factor in the pathogenesis of apnea in certain infants, we compared the frequency of short and prolonged apnea immediately following regurgitation to that during control periods. Ten infants (nine preterm and one term) with histories of frequent regurgitation and also apneic spells were studied for 2 to 3 hours by monitoring nasal airflow, abdominal respiratory movements, electrocardiogram, pharyngeal pH, and pharyngeal pressure. In six of these infants additional observations were made without the intrapharyngeal recording devices. Fourty-four episodes of regurgitation were observed. Both prolonged apnea (P less than 0.05) and short apnea (P less than 0.01) occurred much more frequently during regurgitation than during the control period; however, the majority of prolonged apneic spells observed were unassociated with regurgitation. The increased frequency of apnea during regurgitation was not related to the presence of intrapharyngeal recording devices. Although nasal regurgitation was frequently associated with short apnea, no prolonged apnea was observed during the seven episodes of nasal regurgitation observed. The 14-fold increase in prolonged apnea frequency immediately following regurgitation supports the hypothesis for a causal relationship between apnea and regurgitation.     

Effect of sleep state and position on the incidence of obstructive and central apnea in infants

Sixty-four infants with a history of apnea were studied to determine the effects of sleeping position and sleep state (rapid eye movement [REM]) v (non-rapid eye movement [NREM]) on the occurrence of central and obstructive apneas. All-night polysomnographic studies were conducted on each infant, and the spontaneous occurrence of central and obstructive apneic events was determined in the prone, supine, and side positions. Sleeping position did not significantly affect the rate or duration of central or obstructive apneas. Furthermore, neither central nor obstructive apneic episodes were significantly altered by sleep state. These data suggest that, in spite of an ostensible predisposition to upper airway obstruction in the supine position and during rapid eye movement sleep, neither sleeping position nor sleep state appears to affect the rate of duration of apneic events.     

Efficacy of caffeine in treatment of apnea in the low-birth-weight infant.

The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea.     

Sleep-related abdominal muscle behavior during partial or complete obstructed breathing in prepubertal children

We have evaluated the influence of nonrapid eye movement (NREM), REM sleep, and arousal on abdominal muscle contractions during snoring and/or obstructive apnea in 10 prepubertal children. All children were known habitual snorers and eight had a sleep apnea index above 10. During stage 3-4 non-REM sleep, non-apneic breathing with snoring was always associated with the presence of expiratory abdominal muscle electromyogram (EMG) discharges. During non-REM sleep apneas, abdominal muscle EMG discharges increased from the beginning to the end of each apnea. Termination of non-REM sleep apnea was marked by an "EEG arousal" in 12% of the apneic events and by a "movement arousal" in the other 88%. The highest abdominal muscle EMG discharge was always observed during the arousal response. During "phasic" REM sleep, abdominal muscle EMG discharges were absent during both nonapneic breathing (with or without snoring) and obstructive apneas. All REM sleep apneas ended with a "movement arousal," during which abdominal muscle EMG discharges were observed. Thus, abdominal muscle EMG discharges associated with "arousal" were seen independent of the immediately preceding sleep state.     

Statistical evaluation of respiratory control in infants to assess possible risk for the sudden infant death syndrome (SIDS)

We examined the application of statistical parameters related to respiratory control in order to assess possible risk for the sudden infant death syndrome (SIDS). The suitability of these parameters was tested in 287 infants between 1 day and 6 months of age. Respiration of the infants was recorded during sleep, and duration and frequency of apneic spells was evaluated. All infants were patients of the department of pediatric surgery, and were free of pulmonary, cardiac or cerebral diseases. Of the investigated infants, 54 were assigned as an at risk group, for they had already had demonstrable serious or life threatening apneas or respiratory problems during anesthesia.We computed the frequency distribution of sleep apnea durations, and calculated the respective probabilities for the occurrence of apnea of a certain duration according to age. By analogy with Shannon's well known definition of average information content we defined an entropy term, which formally agrees with the definition of entropy in thermodynamics. This statistical procedure seems to be well suited for the identification of disorders in respiration control possibly related to a risk for SIDS. All at risk infants were treated with aminophylline, and the respiratory state improved significantly in nearly all cases.In some infants QT intervals were evaluated from the ECG recordings during sleep, but no significant differences between risk and control infants could be demonstrated.This study was supported by the Austrian Research Fund     

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogeny of sleep and awake states in relation to breathing in preterm infants.

This review will focus on the development of behavioural states and breathing during early developmental stages prior to term gestation. Although these behavioural states are immature during early development, their cyclicity is clearly seen. Preterm infants characteristically have a large proportion of indeterminate sleep and small amount of wakefulness. Whereas oxygenation is relatively stable during active and quiet sleep in ventilated preterm infants, indeterminate sleep and arousals are associated with hypoxaemic episodes. Arousals have also been linked to apnoea in spontaneously breathing infants. Since well-defined sleep cycles are beneficial for the oxygenation of preterm infants, we should explore ways to promote their natural sleep while they are exposed to neonatal intensive care. Care practices such as clustering procedures, kangaroo care and optimal positioning have been shown to improve the integrity of sleep. Optimizing the sleep cycling might improve the long-term outcome of preterm infants. More studies in this area are clearly needed.     

Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture

We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term.     

Periodic breathing and apnea in preterm infants

The relationship between periodic breathing and idiopathic apnea of prematurity was investigated. We recorded respiratory impedance, heart rate, pulse oximetry and end-tidal CO2 from 68 untreated infants of less than or equal to 34 wk gestation with a diagnosis of idiopathic apnea of prematurity. Mean birth wt was 1476 g (SD 420) and mean gestational age was 29.9 wk (SD 2.6). Apneas of more than 15 s duration that were associated with hypoxemia or bradycardia were identified by semiautomated analysis of computerized records. A total of 1116 significant apneic spells were identified, only one of which occurred during an epoch of periodic breathing, five others occurred within 2 min of the end of an epoch of periodic breathing. Less than 0.6% of significant apneic spells occur within 2 min of periodic breathing. In all of the 12 infants that were monitored starting in the first 12 h of life, significant apneic spells were identified before 36 h of age and no precipitating factors were identified. Periodic breathing did not occur during the first 48 h of life, a finding that supports the concept that the peripheral chemoreceptor is inactive in the first 48 h of life. Periodic breathing in the premature infant is not a precursor to significant apnea.