Effects of hyperoxia on the arousal response to upper airway obstruction in lambs

Experiments were done to investigate the effects of increased inspired oxygen on the arousal response from sleep to upper airway obstruction in 10 newborn lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticograms, electrooculogram, nuchal and diaphragm electromyograms, and measurements of systemic arterial blood pressure and oxygen saturation (fiberoptic catheter oximeter). A tracheotomy was performed and a fenestrated tracheostomy tube was placed in the trachea. A 5F balloon tipped catheter was inserted into the tube so that airflow could be obstructed by inflating the balloon. No sooner than 3 days after surgery, measurements were made during a control period and during an experimental period of upper airway obstruction; the inspired oxygen fraction was alternated hourly between 0.21 and 0.60. A total of 57 epochs of quiet sleep and 58 epochs of active sleep was obtained in eight lambs. Arousal was significantly delayed (p less than 0.005) during active sleep (21 +/- 6 s; mean +/- 1 SD) compared to quiet sleep (7 +/- 2 s) in room air. Increased inspired oxygen significantly delayed arousal (p less than 0.05) during active sleep (47 +/- 25 s), but had little effect on arousal in quiet sleep (10 +/- 4 s). These results provide evidence that arousal from active sleep following upper airway obstruction in lambs is primarily initiated by a decrease in arterial oxygen. However, arousal from quiet sleep following upper airway obstruction in lambs appears to be initiated by other stimuli.     

Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs

Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.     

Naloxone does not alter the arousal response decrement after repeated exposure to hypoxemia during sleep in lambs.

Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs.     

Nicotine delays arousal during hypoxemia in lambs

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.     

Repeated exposure to rapidly developing hypoxemia influences the interaction between oxygen and carbon dioxide in initiating arousal from sleep in lambs

Experiments were done on 12 lambs to determine if repeated exposure to hypoxemia influences the interaction between oxygen and carbon dioxide in causing arousal response from sleep. Each lamb was anesthetized and instrumented for sleep staging and measurements of arterial Hb oxygen saturation. No sooner than 3 days after surgery, measurements were made in quiet and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing either 5% O2-0% CO2, 5% O2-5% CO2 or 5% O2-10% CO2. Each experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen once the animal aroused from sleep. The lambs were divided into two groups. One group (n = 7) was studied without prior exposure to hypoxemia and the other group (n = 5) was studied after exposure to 5% oxygen during approximately 100 epochs of sleep until they aroused. In lambs not previously exposed to hypoxemia, there was evidence for a slight interaction between oxygen and carbon dioxide in initiating arousal but only from quiet sleep. Repeated exposure to hypoxemia resulted in an arousal response decrement to hypoxemia. In lambs previously exposed to hypoxemia, there was evidence for an interaction between oxygen and carbon dioxide in initiating arousal from both quiet and active sleep (i.e. the time to arousal decreased and the saturation at arousal increased as increasing amounts of carbon dioxide were added to the hypoxic gas mixture).(ABSTRACT TRUNCATED AT 250 WORDS)     

Arousal from sleep during rapidly developing hypoxemia in lambs

Arousal is an important protective response that may prevent severe hypoxemia and death during sleep. However, very little is known about arousal from sleep in response to respiratory stimuli in newborns. Experiments were therefore done to investigate the arousal response from sleep to rapidly developing hypoxemia in eight lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial hemoglobin oxygen saturation. A tracheotomy was done and a tracheostomy tube placed in the trachea so that the fraction of inspired oxygen could be changed quickly. No sooner than 3 days after surgery, measurements were made in quiet sleep and active sleep (AS) during 30-s control periods when the animals were breathing 21% oxygen and during experimental periods of hypoxemia when the animals were breathing either 10, 5, or 0% oxygen in nitrogen. During quiet sleep, arousal occurred at similar arterial hemoglobin oxygen saturations (81 +/- 6% on 10% O2, 80 +/- 5% on 5% O2 and 83 +/- 5% on 0% O2) suggesting that arousal was independent of the rate of change of arterial oxygen. However, during AS arousal occurred at different arterial hemoglobin oxygen saturations (76 +/- 6% on 10% O2, 55 +/- 11% on 5% O2, and 44 +/- 17% on 0% O2) suggesting that arousal was dependent on the rate of change of arterial oxygen. During some epochs of AS, electrocortical signs of cerebral hypoxia and primary apnea occurred before arousal. These data provide evidence that arousal from quiet sleep in response to hypoxemia occurs once an arousal threshold has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)     

Depression of Respiratory Muscles and Defective Responses to Nasal Obstruction during Active Sleep in the Newborn

Henderson-Smart, D. J. and Read, D. J. C. (1976). Aust. paediat. J. , 12, 261–266. Depression of respiratory muscles and defective responses to nasal obstruction during active sleep in the newborn. Rib-cage and abdominal movements were recorded during different sleep stages in 22 healthy babies at ages up to 3 months and in 8 older infants up to 10 months. During active sleep, all babies and 6 infants developed: (i) rib-cage collapse during diaphragmatic descent; (ii) overall deflation of the rib-cage. Oesophageal pressure recordings in 7 babies showed that this paradoxical rib-cage motion was not accompanied by increased negativity of intra-pleural pressure, and was therefore not due to intermittent airway obstruction.
In 7 newborn lambs, the development of rib-cage paradox during active sleep was related to a marked reduction of the electromyographic (EMG) activity of intercostal and abdominal muscles. During quiet sleep, nasal occlusion initiated a strong reflex augmentation of intercostal EMG activity and prompt arousal, whereas in active sleep these defensive responses were absent. A reduction of pulmonary O₂-stores and ventilation may result during active sleep, making the newborn baby vulnerable to a rapid development of hypoxaemia, respiratory depression and sudden infant death (crib-death).     

Infant stress and sleep deprivation as an aetiological basis for the sudden infant death syndrome

SIDS is almost invariably sleep-related. Viable syndrome aetiology must be compatible with its many epidemiologically diverse risk factors, each of which directly or indirectly associates with the creation of psychological and/or physiological infant stress, and the subsequent disruption of normal, contented sleep. During essential deep 'rebound' recovery sleep, arousal ability and upper airway muscle tone decrease further to that in normal sleep, with subsequent upper airway obstruction. When stress impact causes sufficient sleep disruption and physiological fatigue, a failure to arouse and so restore sufficient tone to overcome such obstruction results in sudden, unexpected death. SIDS has therefore many causes which share a final lethal mechanical pathway. Evidence is presented for obstructive apnoea during sleep as being the primary syndrome death mode, for sleep disruption, reduced arousal ability, and infant stress in SIDS, and for risk factor association with the creation of this stress. Specific infant vulnerability in the first 6 months of life to stress predominantly related to total dependency on a carer for gratification of need, and to obstructive sleep apnoea due to normal anatomical, physical, and respiratory immaturity, including rapid physiological fatigue, and peaks in sleep and thermal stress vulnerability, are discussed. Further reasons for the limited age period of SIDS, and for reduced neonatal risk, are given. Prone sleeping risk can relate to positional airway obstruction during normal sleep without prior infant stress. Much of SIDS aetiology appears to concern factors related to socio-economic deprivation and subsequent sub-optimal infant care.     

Effects of carotid body maturation and terbutaline on the laryngeal chemoreflex in newborn lambs

The response to laryngeal chemoreflex (LCR) water stimulation was compared in unanesthetized awake 4- to 10-day-old preterm and 2- to 4-wk-old term lambs before and after infusion of a beta-adrenergic agonist, terbutaline, given pre- and postcarotid body denervation (CBD). Ventilation decreased more in response to LCR stimulation post-CBD in the older lambs. CBD did not change the respiratory response to LCR stimulation in the younger lambs. LCR stimulation resulted in less bradycardia post-CBD in both groups. Terbutaline significantly attenuated the LCR response in the older lambs pre-CBD but not post-CBD. LCR respiratory response was not changed in the younger lambs when terbutaline was infused, pre- or post-CBD. Compared to wakefulness, the LCR response in preterm lambs was greater in sleep not associated with arousal. If arousal occurred, LCR response during sleep did not differ from that during wakefulness. The incidence of arousal decreased markedly after CBD, suggesting that arousal is modified by the carotid bodies. It is concluded that the carotid bodies modify the reflex response to LCR stimulation in 2- to 4-wk-old lambs. During the 1st postnatal wk, preterm lambs have a reduced carotid body function during wakefulness and, therefore, a decreased hypoxic ventilatory response and increased respiratory response to LCR stimulation. The attenuating effect of terbutaline on LCR response is partially related to mature carotid body function.     

The prone sleeping position impairs arousability in term infants

OBJECTIVE: To investigate whether the prone sleeping position impaired arousal from sleep in healthy infants and whether this impairment was related to cardiorespiratory variables, temperature, or age.Study design: Healthy term infants (n = 24) were studied with daytime polysomnography on 3 occasions: 2 to 3 weeks after birth, 2 to 3 months after birth, and 5 to 6 months after birth. Multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both active sleep and quiet sleep when infants slept prone at 2 to 3 weeks and 2 to 3 months, but not at 5 to 6 months. These increases were independent of any sleep position-related change in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation, or heart rate. CONCLUSIONS: The prone position significantly impairs arousal from both active sleep and quiet sleep in healthy term infants. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory variables or body temperature. Decreased arousability from sleep in the prone position provides an important insight into its role as a risk factor for sudden infant death syndrome.     

Detection of sleep associated dysfunctional pharyngeal obstruction in infants

Six infants were referred with symptoms and clinical signs suggesting airway obstruction during sleep. In each case, overnight recordings of arterial oxygen saturation, respiratory movements and end tidal expired carbon dioxide (ETCO₂) showed the presence of abnormal episodes of hypoxaemia related to partial or complete airway obstruction and associated with a specific pattern of the inspiratory movement waveforms. These events and patterns were not found on recordings from 20 age-matched healthy infants and young children. ETCO₂ levels were also abnormally elevated in all six patients when asleep. Fiber-optic upper airway endoscopy excluded structural abnormalities, including significant tonsillar or adenoidal enlargement, but showed an intermittent dysfunctional inspiratory obstruction in the pharynx. Continuous positive airways pressure and tracheostomy were effective in treating this obstruction.Abbreviations CPAP continuous positive airways pressure - ETCO₂ end tidal carbon dioxide - SaO₂ arterial oxygen saturation     

Effects of prior hypoxia exposure, endotoxin and sleep state on arousal ability to airway obstruction in piglets: implications for sudden infant death syndrome

BACKGROUND: Respiratory tract infections may be an important component in many deaths attributed to sudden infant death syndrome (SIDS), although the mechanism of involvement remains unclear. OBJECTIVES: The hypothesis was tested that prolonged hypoxia and a thermogenic state (simulating a fever due to respiratory tract infection) would impair respiratory responsiveness to airway obstruction during sleep. METHODS: Thirty nine piglets aged 5-7 days were exposed to 24 h of moderate hypoxia and/or a low dose of endotoxin derived from Salmonella abortus equi. Responsiveness to complete and subtotal upper airway obstruction was tested during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The end-point for airway obstruction tests was taken as the first protective response, either arousal or initiation of mouth breathing. Responsiveness was assessed as response time and response threshold (measured as respiratory effort, i.e. esophageal pressure swing). RESULTS: All animals demonstrated a thermogenic state following endotoxin delivery (drop in ear temperature of 5.8 +/- 0.2 degrees C and a small but significant increase in rectal temperature). Response time to subtotal airway obstruction was reduced during the heat conserving phase of the fever (thermogenesis; 2.8 +/- 0.5 s compared to 4.3 +/- 0.7 s during pre-endotoxin tests), but markedly increased during the recovery period (20.3 +/- 5.1 compared to 14.0 +/- 2.5 s pre-endotoxin) in NREM sleep. Response threshold was not significantly affected by either endotoxin or hypoxia in NREM sleep. Respiratory responsiveness to subtotal obstruction was markedly reduced during REM sleep (response time 40.3 +/- 10.9 s compared to 14.7 +/- 2.2 s in NREM; response threshold -14.0 +/- 1.3 mm Hg compared to -11.7 +/- 1.0 mm Hg in NREM). CONCLUSIONS: This study has demonstrated in a neonatal animal model that respiratory responsiveness to airways obstruction is delayed during recovery from fever. The findings may have implications for the human infant recovering from a respiratory illness.     

Breathing patterns, oxygen and carbon dioxide levels in sleeping healthy infants during the first nine months after birth

Data on arterial oxygen saturation (SaO2), transcutaneous PO2, pCO2 (tcpO2, tcpCO2) and breathing patterns in sleeping healthy term infants were obtained during the first 9 mo after birth. Forty-four healthy infants, mean GA at birth 40 +/- 1.0 wk, mean BW 3520 +/- 562 g were examined between 2 wk and 9 mo postnatally in a cross-sectional study. SaO2, tcpO2, tcpCO2, heart rate (HR), rib cage and abdominal respiratory movements were recorded during natural nocturnal sleep, stratified for sleep states (active sleep (AS), indeterminate sleep (IS), quiet sleep (QS)). The data on AS and IS were pooled as in previous studies. The variables were analysed with respect to age. SaO2 in AS + IS and QS was 96.1 +/- 1.3%, 96.6 +/- 1.4%, respectively. TcpO2 in AS + IS was 10.6 +/- 1.1 kPa and 10.7 +/- 1.3 kPa in QS, while tcpCO2 in AS + IS was 5.4 +/- 0.3 kPa and 5.4 +/- 0.4 kPa in QS. Neither SaO2 nor tcpO2 was influenced by age. TcpCO2 decreased significantly postnatally. Five infants (11.3%) experienced episodes of hypoxaemia with a mean decrease in SaO2 to 86 +/- 1.5%. In four infants these hypoxaemic episodes were linked to upper airway obstructions. Episodes of SaO2 < 90% in conjunction with a decrease in HR to < 100 bpm were detected in one infant only. Periodic breathing (PB) was observed in 38.6% of infants. Conclusion: Oxygenation and carbon dioxide levels in sleeping healthy term infants were comparable to those reported in older children. Hypoxaemic episodes, if present, are associated with upper airway obstruction. PB, often assumed to be a pathological feature, is a normal breathing pattern in this age group.     

Arterial oxygen tension threshold range for the onset of arousal and breathing in fetal sheep.

Mechanisms for the control of episodic fetal breathing movements or the onset of continuous breathing at birth remain unknown. Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce arousal and continuous breathing. To investigate 1) the threshold range of arterial oxygen tension (PaO2) for the onset of arousal and breathing and 2) the graded response of breathing to various levels of PaO2, we studied 10 fetal sheep between 135 and 142 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, arterial pH, and blood gas tensions. PaO2 threshold was determined through an indwelling O2 sensor catheter. Fetal lungs were distended at a continuous positive airway pressure of 40 cm H2O with 100% N2 or with O2 ranging from 40 to 100% via an in situ endotracheal tube. At the onset of arousal (n = 10), PaO2, arterial carbon dioxide tension, and Hb O2 saturation increased from control values of 21.7 +/- 0.75 torr (2.9 +/- 0.09 kPa), 41.8 +/- 1.1 torr (5.47 +/- 0.15 kPa), and 52.9 +/- 2.6% to 65.6 +/- 9.6 torr (8.74 +/- 1.28 kPa), 46.9 +/- 1.3 torr (6.25 +/- 0.17 kPa), and 92.9 +/- 2.06%, respectively, whereas the pH decreased from 7.31 +/- 0.006 to 7.27 +/- 0.009 (mean +/- SEM; p = 0.001, 0.04, 0.002, and 0.001, respectively). Seven of 10 fetuses breathed continuously. In these fetuses, PaO2 and arterial carbon dioxide tension further increased and pH decreased; however, no further significant increase in Hb O2 saturation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemoglobin desaturation during sleep and daytime in patients with cystic fibrosis and severe airway obstruction

Transcutaneous hemoglobin saturation by pulse oximetry was evaluated during sleep and for 2-3 h during the day in 31 patients with cystic fibrosis (median age 15.2 years; range 7.6-33.6 years) and severe airway obstruction. Pulse oximetry readings were analyzed as a cumulative percentage of time in which oxygen saturation was < 90% during both sleep and daytime. Each patient was also examined using clinical and radiological scores, spirometry and arterial blood-gas analysis. The agreement between arterial and transcutaneous saturation was evaluated in 29 patients. The difference between transcutaneous and arterial saturation was 2.4 +/- 2.0% and it increased as arterial saturation decreased. Clinical and radiological scores and spirometry parameters showed a poor correlation with both overnight and daytime desaturation. An arterial saturation < 94% may indicate a risk of consistent desaturation. This occurred for more than 50% of the time in 11 of 20 patients during sleep and in 5 of 20 patients during daytime hours.     

A review of the anatomy of the upper airway in early infancy and its possible relevance to SIDS

BACKGROUND: Since the danger of prone sleeping in the first 6 months of life has been publicised, there has been a dramatic and consistent reduction in the incidence of sudden infant death syndrome (SIDS). However, unexpected infant deaths and apparent life-threatening events (ALTEs) continue to occur that are clearly not associated with known epidemiological risk factors. AIMS: To review the unique features of the anatomy and function of the upper airway of the young infant which contribute to increased vulnerability to hypoxia in this age group. We discuss the clinical identification of those infants at risk of obstruction or restriction of the upper airway and the management of the 'at risk' infant. CONCLUSIONS: In the era after the "back to sleep" campaigns, it is likely that an increasing proportion of cases of ALTEs and SIDS will be related to obstruction or limitation of upper airway size leading to sleep hypoxia/asphyxia. This type of problem may be anticipated by evaluation and investigation of infants with signs or a clinical history consistent with possible upper respiratory tract compromise, including micrognathia.     

Fever in young lambs: carotid denervation alters the febrile response to a small dose of bacterial pyrogen.

Experiments were done on 13 young lambs to determine if carotid denervation influences the cardiovascular and metabolic responses to i.v. administration of bacterial pyrogen [Salmonella abortus equi (SAE) 0.3 micrograms]. Each lamb was anesthetized with halothane and prepared for measurements of cardiac output, arterial and mixed venous oxygen saturations, and body core temperature. No sooner than 3 d after surgery, measurements were made during a control period and at 10-min intervals for 120 min after i.v. administration of SAE in seven carotid-intact lambs and six carotid-denervated lambs. Administration of SAE produced a short-lived fever of about 1 degrees C in the carotid-intact lambs, whereas no change in body core temperature was observed in the carotid-denervated lambs. In carotid-intact lambs, the rise in body core temperature began approximately 40 min after administration of SAE and continued for approximately 50 min. This rise in body core temperature was preceded by the onset of shivering and an increase in total body oxygen consumption. Carotid denervation produced changes in some of the cardiovascular variables during the control period (i.e. arterial oxygen content, cardiac index, heart rate, and pulmonary blood pressure); however, there were no additional significant changes in any of the metabolic or cardiovascular variables after administration of SAE. The mechanism of these unexpected findings remains to be determined.     

Hypoxic arousal responses in infants with bronchopulmonary dysplasia

Infants with bronchopulmonary dysplasia have a high incidence of sudden, unexplained death in the postneonatal period, yet the cause of these deaths is unknown. Frequent episodes of clinically unsuspected arterial oxygen desaturation have recently been described in infants with bronchopulmonary dysplasia. We hypothesized that infants with bronchopulmonary dysplasia who experience frequent episodes of hypoxia may have abnormal arousal responses to these hypoxic episodes. We studied 12 infants with bronchopulmonary dysplasia at 41.4 +/- 1.3 weeks postconceptional age. Hypoxic arousal responses were performed during quiet sleep at an inspired oxygen tension of 80 mm Hg for a maximum of three minutes or until arousal occurred. Of 12 infants, 11 (92%) aroused normally to the hypoxic challenge. However, all infants required vigorous stimulation and supplemental oxygen after the initial arousal response. Of 12 infants with bronchopulmonary dysplasia, eight (67%) experienced prolonged apnea with bradycardia, and four of 12 (33%) required brief ventilatory assistance (bag and mask) to restore normal breathing. Abnormal pneumographic findings did not predict the occurrence of these prolonged periods of apnea and bradycardia following hypoxia. We conclude that an abnormal response to hypoxia following arousal may lead to prolonged apnea and bradycardia in infants with bronchopulmonary dysplasia. We speculate that the inability to recover from this hypoxia may result in sudden death in these infants.     

Respiratory syncytial virus infection enhances the response to laryngeal chemostimulation and inhibits arousal from sleep in young lambs*

To evaluate the effect of respiratory syncytial virus (RSV) infection on the response to laryngeal chemostimulation (LCS) with water, five lambs were inoculated with human RSV and three lambs were given control media at an age of 3-5 days. During RSV infection, LCS resulted in increased inhibition of minute ventilation and delayed recovery of regular breathing. Sleep further increased the response, and arousal was less likely to occur in active sleep. Two of the five infected lambs needed resuscitation after LCS when arousal was absent. Histological studies showed bronchiolitis and pneumonitis. Laryngeal tastebud morphology was unchanged at 8 days after inoculation. However, infected lambs had disrupted tastebuds 4-6 weeks after infection. Failure to arouse and to terminate reflex apnea may play a role in the pathogenesis of the sudden infant death syndrome associated with respiratory tract infection.     

Transcutaneous oxygen saturation in sleeping infants: prone and supine.

Pulse oximetry was used to measure transcutaneous arterial oxygen saturation in infants aged 2 to 11 months prone and supine in quiet sleep. Groups of healthy infants (n = 34), infants with upper respiratory tract infections (n = 13), and infants with generalised moderately severe lower respiratory tract infections (n = 17) were studied. No clinically important differences were demonstrated in any of these groups, although there was a small advantage in the prone position in the group with lower respiratory tract infection. The effect of posture on infants with more severe lower respiratory tract infection and during active sleep has yet to be determined.