Sleep state organization in the developing piglet during exposure to different thermal stimuli.

Sleep state changes in response to different thermal stimuli were investigated in newborn piglets between 2 and 10 days of age. Test animals were exposed to cold air (7-12 degrees C) and warm air (27-33 degrees C) around the face, while the remainder of the body was kept at first warm (normothermic) then hyperthermic. A separate group of animals was studied under normothermic conditions (control) for the duration of the study. Piglets showed typical changes in sleep state patterns characteristic of rapid maturation over the first 10 days of development. It was found that both the amount of rapid eye movement (REM) sleep and, in some cases, the duration of REM episodes increased in response to facial cooling regardless of rectal temperature. However, hyperthermia with warm air exposure caused a significant decrease in the amount of REM sleep but not in the duration of REM episodes. It is suggested that an infant placed to bed in a cold room or exposed to a draft might also experience a greater amount of REM sleep than an infant placed to sleep in a warm draft-free room.

Thermal balance in infants.

A theoretical model of heat balance is presented that could clarify the matching of babies' wrapping with their environments. Best estimates of metabolic heat input and heat loss by all known routes are defined for 22 parts of the body surface. The variation of these with core temperature, posture, skin vasodilatation, and the onset of sweating are calculated: first, by using presumed skin temperatures and second, by following iterative calculation of the skin temperature and the consequent total heat losses. Calculation of the highest tolerable ambient temperature (HTAT) for a given set of clothes, underbedding, and covers shows that a well-wrapped baby lying face down could have an HTAT 10 degrees C lower than if he/she were lying supine. Representative values for highest and lowest tolerable temperatures (defined in text) are presented for the first 6 mo of life. Retrospective estimation of thermal balance from death-scene data on clothing and bedding can permit assessment of hyperthermia or hypothermia as a contributing cause of death. Recommendations are made on the avoidance of hyperthermia.

Sleep position, autonomic function, and arousal.

AIMS: To investigate and compare heart rate variability (HRV) and responses of heart rate and arousal to head-up tilting in infants sleeping prone and supine. METHODS: Thirty seven healthy infants aged 2-4 months were studied. HRV was measured for 500 beats while they were in a horizontal position. Subjects were then tilted 60 degrees head-up, and heart rate recorded over 1 minute and arousal responses observed. Data were collected during both quiet and active sleep for both prone and supine sleep positions. RESULTS: HRV, as assessed by the point dispersion of Poincaré plots, was significantly reduced in the prone position for both sleep states. Sleep position did not influence the changes in heart rate seen during a head-up tilt. Full awakening to the tilt was common in active sleep but significantly less so in the prone position (15% of prone tests vs 54% supine). Full awakening to the tilt rarely occurred during quiet sleep in either sleep position. CONCLUSION: This study provides some evidence that blunted arousal responses and/or altered autonomic function are a feature of the prone sleeping position. Decreased HRV may be a sign of autonomic impairment. It is seen in many disease states and in infants who later die of sudden infant death syndrome (SIDS).

Respiratory responses to hypoxia/hypercapnia in small for gestational age infants influenced by maternal smoking.

AIM: To determine any variation in the respiratory responses to hypoxia/hypercapnia of infants born small for gestational age (SGA) to smoking and to non-smoking mothers. METHODS: A total of 70 average for gestational age (AGA) infants (>36 weeks gestation, >2500 g, >25th centile for gestational age, and no maternal smoking), and 47 SGA infants (<10th centile for gestational age) were studied at 1 and 3 months of age, in quiet and active sleep. Respiratory test gases were delivered through a Perspex hood to simulate face down rebreathing by slowly allowing the inspired air to be altered to a CO(2) maximum of 5% and O(2) minimum of 13.5%. The change in ventilation with inspired CO(2) was measured over 5-6 minutes of the test. The slope of a linear curve fit relating inspired CO(2) to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). RESULTS: There was no significant difference in VAS between the AGA and SGA infants (0.25 v 0.24). However within the SGA group, VAS was significantly higher (p = 0.048) in the infants whose mothers smoked during pregnancy (0.26 (0.01); n = 24) than in those that did not (0.23 (0.01); n = 23). The change in minute ventilation was significantly higher in the smokers than the non-smokers group (141% v 119%; p = 0.03) as the result of a significantly larger change in respiratory rate (8 v 4 breaths/min; p = 0.047) but not tidal volume. CONCLUSIONS: Maternal smoking appears to be the key factor in enhancing infants' respiratory responses to hypoxia/hypercapnia, irrespective of gestational age.

Arousal responses of the newborn piglet to airways obstruction and rebreathing during normothermia and hyperthermia.

Most experimental studies of arousal to respiratory stressors have been performed under neutral thermal conditions. The present study focussed on arousal responses with the added challenge of heat stress. The subjects were two groups of 10 sedated piglets aged 4-6 days and 2-6 days respectively. Respiratory stimuli (partial and total airways obstruction (AO) or rebreathing (RB) expired gases) were applied during non-rapid-eye-movement (NREM) sleep. Measurements of heart rate, SaO2, intra-pleural pressure or inspired CO2 and O2 were recorded during tests in normothermia and hyperthermia. Hyperthermia significantly shortened the time to arousal. Thus, arousal times from partial and total AO and from RB were: in normothermia, 40.3 +/- 5.8, 9.2 +/- 0.7 and 94.9 +/- 14.7 s respectively; in hyperthermia, 17.8 +/- 3.7, 7.6 +/- 0.9 and 68.5 +/- 9.1 s respectively. Cardio-respiratory variables at arousal were similar in both thermal states. Seven non-sedated piglets were challenged with RB stimuli during normothermia only to determine the influence of sleep state on arousal. Arousal in REM sleep was delayed approximately 2-3-fold (NREM, 41.2 +/- 8.2 s; REM, 88.5 +/- 18.1 s), occurring at a lower SaO2 and higher inspired CO2. It is concluded that arousal from NREM sleep under adverse conditions of hyperthermia shortens the arousal time from asphyxial stimuli induced by AO and RB with no change in the arousal threshold.

Vasoconstriction following spontaneous sighs and head-up tilts in infants sleeping prone and supine.

The cutaneous vasoconstrictor responses following a 60 degrees head-up tilt and a spontaneous sigh were measured in 36 infants at 1 and 3 months age to investigate the effects of age, sleep state and sleep position on these responses. The vasoconstrictor response was determined by a measure of cutaneous blood flow using a laser Doppler flowmeter. The mean reduction in blood flow (vasoconstriction) was 52% following the tilt, and 33% following the sigh. Prone positioning 1-month-old infants as compared to supine, reduced the degree of vasoconstriction following the tilt (P=0.027) and sigh (P=0.026). The supine to prone reduction was: tilt, -11% in quiet sleep (QS) (from 55.1 to 49.1% vasoconstriction) and -18% in active sleep (AS) (from 52.0 to 42.9%) and; sigh, -26% in QS (35-26%), and -15% in AS (31-26%). The degree of vasoconstriction following the sigh was significantly greater in 3- compared to 1-month-old infants (+26%, P=0.040). The mean response to the tilt in the older age group was 12% greater but this did not reach significance (P=0.069). Sleep state did not affect the degree of vasoconstriction but influenced transmission of the response so that latency to minimal vasoconstriction was 1 s shorter in AS than QS. This study provides data on two simple measures of sympathetic activity during sleep that have not previously been described in any detail in infant studies, and add more evidence that autonomic activity is reduced in the prone position compared to supine during sleep.

The prevalence of immature respiratory control in a neonatal population.

Cot death could be the result of chance coincidence of an adventitious challenge and a baby ill-equipped to meet it. This work was designed to test the hypothesis that there is a subpopulation of babies who lack the appropriate responses to hypoxia and hypercapnia which would enable them to overcome the effects of, for instance, nasal obstruction. The responses of 630 babies to air mixtures which induced significant changes in ventilation in the overwhelming majority, were recorded in a short protocol in which both the addition and withdrawal of hypercapnia and of hypoxia were effected. The results of each test were placed in one of five categories; in 13.6% there was no response to hypoxia, and in 2% the ventilation fell in hypoxia to a significant degree. The study confirms the existence of a subgroup of normal babies with little defence to the respiratory loading of mild upper respiratory tract infections.

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.

Diffusional inhomogeneity: gas mixing efficiency in the new-born lung.

1. The results of 105 nitrogen washouts on seventy-six new-born babies are presented; the mean lung volume (functional residual capacity, FRC) of the seventy-six babies measured at more than 1 hr of age was 77.5 +/- 2.9 (S.E. of mean; S.D. = 25.4). 2. The mean gas mixing efficiency was 0.466 +/- 0.0097 (S. E. of mean; S.D. = 0.096). The reasons for the difference between this figure and the normal for adults of 0.66--0.76 are discussed, and it is suggested that the very much greater turnover rate of gas within the lungs is responsible for diffusion inefficiency. 3. Calculations indicate that there is a tenfold fall in diffusion inefficiency for every 9.8 sec turnover time (the time for VE to equal VFRC). In the baby the turnover time is 5--6 sec on average but with a very wide spread; in the adult it is of the order of 30 sec, so that diffusion inefficiency of gas in the lung would be only 0.001 or 0.1%. 4. The significance of this is that the effective alveolar ventilation of the average neonate is less than half the total ventilation (as opposed to two-thirds if deadspace only is considered), becoming a smaller fraction of VE on hyperventilation. This would explain discrepancies in the calculation of alveolar carbon dioxide levels from the output of that gas and the non-deadspace ventilation.

Analysis and interpretation of turning points and run lengths in breath-by-breath ventilatory variables.

Three healthy young male volunteers were studied for 10 min periods of steady-state ventilation under the following conditions: air breathing, 50% inspired oxygen, hyperoxic hypercapnia and hypoxic hypercapnia. Eight variables were recorded breath-by-breath: inspiratory and expiratory tidal volumes, mean flows and durations, total breath duration and expiratory ventilation. Each resulting sequence of breath-by-breath data was analysed in terms of the number of 'turning points' in the sequence and the concomitant mean 'run length' between turning points. The mean run length for all these variables was 1.600, 1.599 and 1.592 in the three subjects. These values are significantly greater than the expected value of 1.5 for random data sequences. There were no consistent significant differences between variables or subjects. Under conditions of hypoxic hypocapnia the mean run length of all variables was found to be 1.666, 1.724 and 1.568 in the three subjects. The two higher values corresponded with periodic breathing of period 10-30 s. These observations are lower than previously published values. A number of ways of interpreting a mean run length of greater than 1.5 are suggested.

Ventilation and sleep state in the new-born.

1. Ventilation, oesophageal pressure and sleep state were measured in fourteen babies between 25 hr and 7 days of age.2. Trunk plethysmograph records showed that respiratory rate and minute volume were significantly higher in REM sleep than non-REM sleep. Tidal volume was not significantly altered.3. Tidal volume, respiratory rate and minute volume were all more variable in each baby in REM sleep, both on breath to breath analysis and over successive 20 sec periods.4. Major oesophageal peristaltic activity was observed in REM sleep only.5. In response to a sharp rise in P(O2) the tidal volume and minute volume fell significantly by the same proportion in both sleep states. Respiratory rate did not change significantly.

Comparison of two methods of determining asphyxial potential of infant bedding.

OBJECTIVE: To establish, with the use of live sedated piglets on a range of bedding surfaces, the possibility of asphyxia when an infant is breathing face down into infant bedding surfaces, and to compare the results with those obtained with a mechanical model. METHODS: Piglets underwent tracheotomy and were attached to a silicon rubber model head of a 3-month-old infant. This was placed face down on bedding surfaces, and respiratory and blood gas data were collected for a 60-minute period. RESULTS: All bedding surfaces but one showed some rebreathing. This was to lower levels than with the mechanical model, but the ranking of the surfaces by level of rebreathing was similar. Two piglets died within the 1-hour experimental time. CONCLUSION: It is confirmed that the data from a mechanical model of rebreathing on different bedding surfaces are matched by those derived from a piglet model that responds normally to asphyxia.

The effect of positive end expiratory pressure on rebreathing and gas dilution in the Ayre's T-piece system--a laboratory study.

The effect of positive end expiratory pressure on the function of the Ayre's T-Piece System was studied using a simple lung model. Positive end expiratory pressure did not effect end tial CO2 during "controlled breathing" but caused an increase during "spontaneous breathing" when fresh gas flow was less than 3 times the minute volume. Gas dilution did not occur under any of the test conditions.

Apnea and rapid eye movement sleep excess in the piglet during recovery from hyperthermia.

This investigation tested the hypothesis that artificially induced mild hyperthermia and recovery from hyperthermia in the developing newborn piglet (2-10 d of age) alter sleep state patterns and respiratory control. Continuous measurements of sleep state, respiratory pattern, carbon dioxide production and oxygen consumption were made before, during, and after a 3-h period of sustained hyperthermia. During hyperthermia, rectal temperatures were raised a mild 1-1.5 degree C above normal, well below the levels likely to cause severe physiologic distress in this species. This resulted in a disruption of the sleep state pattern characterized by a decrease in duration of rapid eye movement (REM) episodes, whereas immediately afterwards, during recovery, the amount of REM sleep increased. In some cases the amount of REM sleep in recovery more than doubled the basal level. Apneas were rarely observed during hyperthermia, but in recovery there was an increase in the total amount of time spent in apnea in both REM and non-rapid eye movement sleep states with a predominance in the REM state. Arousal responses to chemostimulation were not affected at this time. We conclude that the sleeping newborn piglet does indeed show marked changes in sleep state pattern (particularly REM sleep) and in the amount of apnea recorded during and immediately after only a mild increase in core temperature.

Respiratory stimulants in treatment of perinatal asphyxia.

The effects of two analeptic drugs-taloximine and ethamivan-have been studied in asphyxiated fetal and newborn rabbits. In primary apnoea ethamivan reduced the time before the onset of gasping, while during gasping taloximine increased the gasp rate. In secondary apnoea neither drug initiated respiration, though most animals could be resuscitated by using intermittent positive pressure respiration. From these results it is suggested that analeptic drugs have no place in obstetric or neonatal departments.

Oxygen consumption in the newborn piglet during combined cold face/hot body exposure.

There is increasing evidence that hyperthermia can occur in cool climates because of overwrapping and that this practice precedes many deaths labelled as SIDS. We have attempted to test the hypothesis that the interaction of a cold face and a hot body might lead to further hyperthermia in a piglet model. Twelve non-sedated newborn piglets were studied over the first 10 days of development. Oxygen consumption was measured continuously during sleep. Animals were exposed to cold face conditions initially while the animal's body was kept warm and then while the body was hyperthermic. The results show that stimulation of the face with cool ambient air during conditions of raised metabolic activity (hot body) causes a fall in oxygen consumption towards basal levels. These studies do not, therefore, support the hypothesis that a further increase in metabolic rate occurs during combined cold face and hot body exposure in the piglet model.

Endotoxin effects on markers of autonomic nervous system function in the piglet: implications for SIDS.

The hypothesis was tested in 30 newborn piglets that the effects of a low dose of endotoxin (1 microg i.v. bolus; Salmonella abortus equi) would impair autonomic nervous system function. Two tests of autonomic function were performed following external warming (pre-endotoxin) and during endotoxin-generated thermogenesis: (1) analysis of heart rate variability in the time and frequency domains and (2) baroreflex sensitivity measured following intravenous injection of the vasoactive drugs nitroprusside and phenylephrine. Beat-to-beat heart rate variability (SDDeltaRR) fell by 2.2 ms from 7.0 ms before fever (p < 0.05). Low-frequency spectral power fell by 2.4 ms(2) from 4.1 ms(2) before fever (p < 0.05). The sensitivity of the baroreflex to changes in blood pressure induced by the vasoactive drugs decreased during fever by 0.72 ms/mm Hg for the nitroprusside test (p < 0.0005) and by 0.31 ms/mm Hg for the phenylephrine test (p < 0.005). These results indicate that in the piglet the balance of autonomic tone is altered and autonomic responsiveness reduced during the thermogenic phase of a fever. These findings are consistent with known risk factors for sudden infant death syndrome.

The micro-environment of the sleeping newborn piglet covered by bedclothes: gas exchange and temperature.

This study followed the thermal and gaseous micro-environment of the newborn piglet sleeping under two levels of bedding insulation. After 1 h in the piglet's thermal comfort zone, the head of each piglet was covered for 2 h with bedding either 12 mm or 21 mm thick. Body temperature rose rapidly, but the arterial gases showed no change in the direction of asphyxia; with the thicker covering PaO2 was unchanged and PaCO2 fell and pH rose. These changes were despite a small rise in environmental PCO2 and fall in PO2 but were also minimized by the piglet's ability to avoid profound hypocapnia by panting at a very low tidal volume. No significant changes in blood gases occurred with the thinner bedding; the temperature rose markedly but more slowly. It is suggested that human babies submerged under bedclothes for any length of time would be more likely to succumb to the effects of hyperthermia than of asphyxia.

Responses to an increasing asphyxia in infants: effects of age and sleep state.

Infants aged 0-6 months were assessed for respiratory and arousal responses to mild asphyxia during sleep. Ventilatory sensitivity was assessed from the relationship between inspired carbon dioxide (FICO2) and ventilation. Arousal and ventilatory sensitivity were significantly related. Respiratory response increased with age and was greater in quiet sleep than in REM sleep. Arousal occurred more frequently in REM sleep (55/102) than quiet sleep (38/165, P < 0.05) and more frequently at the newborn age (54/117) than at 6 months (13/58, P < 0.05). Arousal in quiet sleep occurred in babies with high ventilatory sensitivities (mean ventilatory asphyxial sensitivity (VAS) 0.476 +/- 0.288) and in REM sleep was more associated with low ventilatory sensitivities (mean VAS 0.194 +/- 0.334, P <0.05). We conclude infants respond to mild asphyxia during sleep with an increase in ventilation, an arousal or both. The exact response is dependent on age and sleep state.

A potential danger of bedclothes covering the face.

Investigations of infants dying unexpectedly have reported up to 28% being found completely under bedding. No detailed physiological studies looking at the possibilities of asphyxia in this situation are available. The aim was to determine the potential for asphyxia under different types and thicknesses of bedding. A mechanical model of a 3-month-old infant's respiratory system was used. Bedding was positioned over the head in a supine position, and inspired carbon dioxide recorded. With a fixed respiratory rate and tidal volume, carbon dioxide accumulation increased with increasing layers of blankets. Up to 8.3% inspired carbon dioxide was recorded with more than four layers of blankets. A cotton sheet between the face and blankets reduced the accumulation by half. An infant found dead under bedding may have been exposed to an asphyxial stress. Suffocation from rebreathing trapped, expired gases can be a cause of death in this situation.