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Biomedical subjects

B T Thach

Publications and source records attributed to B T Thach.

At least 19 recordsLinked to original sources

Maturation and transformation of reflexes that protect the laryngeal airway from liquid aspiration from fetal to adult life.

Several reflexes are initiated in the fetus and newborn when hypochloremic or strongly acidic solutions contact the epithelium that surrounds the entrance to the laryngeal airway. These reflexes, known collectively as the laryngeal chemoreflex (LCR), include startle, rapid swallowing, apnea, laryngeal constriction, hypertension, and bradycardia. Many studies have shown that prolonged apnea associated with the LCR may be life threatening and might conceivably be a cause of sudden infant death syndrome. This certainly may be true, but the concept of a lethal LCR paradoxically contrasts with the view that these several reflexes have an important airway-protective role. As the infant matures, rapid swallowing and apnea become much less pronounced, whereas cough and possibly laryngeal constriction become more prominent. This transformation is primarily related to central neural processing rather than to changes in the airway mucosal "water receptors" that initiate the reflex. The LCR develops in the fetus, in an all-aqueous environment, during a period in which aspiration of amniotic fluid poses a serious threat to life. This and other considerations suggest that the transformation in LCR responses from fetal to adult life can be viewed as functionally appropriate to their primary role in defending the airway from aspiration. The laryngeal "water receptors" that initiate the LCR in infants and adults alike appear to be the primary sensory mechanism for defending the airway from aspiration of liquids.

Adaptation, Physiological↗

Inspired CO(2) and O(2) in sleeping infants rebreathing from bedding: relevance for sudden infant death syndrome.

Some infants sleep facedown for long periods with no ill effects, whereas others become hypoxemic. Rebreathing of expired air has been determined by CO(2) measurement; however, O(2) levels under such conditions have not been determined. To evaluate this and other factors influencing inspired gas concentrations, we studied 21 healthy infants during natural sleep while facedown on soft bedding. We measured gas exchange with the environment and bedding, ventilatory response to rebreathing, and concentrations of inspired CO(2) and O(2). Two important factors influencing inspired gas concentrations were 1) a variable seal between bedding and infants' faces and 2) gas gradients in the bedding beneath the infants, with O(2)-poor and CO(2)-rich air nearest to the face, fresher air distal to the face, and larger tidal volumes being associated with fresher inspired air. Minute ventilation increased significantly while rebreathing because of an increase in tidal volume, not frequency. The measured drop in inspired O(2) was significantly greater than the accompanying rise in inspired CO(2). This appears to be due to effects of the respiratory exchange ratio and differential tissue solubilities of CO(2) and O(2) during unsteady conditions.

Air↗

Sudden infant death syndrome: can gastroesophageal reflux cause sudden infant death?

Although gastric contents in the airways and lungs of sudden infant death syndrome (SIDS) victims is commonly found during postmortem examination, its significance as a sole or contributory cause of death has long been controversial. Currently, most authorities view such aspiration as resulting from "agonal" processes and, therefore, irrelevant to cause of death. Recent clinical and experimental evidence indicates that infants who are near death because of a variety of conditions, frequently "autoresuscitate," which produces rapid and complete recovery. In animal models, aspiration of water or saline into the airways has been shown to prevent autoresuscitation. In light of these findings, aspiration of gastric contents should be reconsidered as a contributory cause of many SIDS deaths.

Forensic Medicine↗

Sleep influences on homeostatic functions: implications for sudden infant death syndrome.

The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The deficits appear to involve alterations in neurotransmitter receptors within regions involved in chemoreception and cardiovascular control. SIDS risk is enhanced by pre- and postnatal nicotine exposure, and possibly by hypoxic experiences. The prone sleeping position plays a significant role in risk, as do head positions that minimize facial escape from enclosed spaces; elevated body temperature may also be a factor. Compensatory mechanisms, including diminished gasping ability, relative failure to arouse to a safer state, or a failure to recruit respiratory efforts to overcome a blood pressure loss have been the object of recent research efforts. The findings suggest that the fatal event involves a neurally-compromised infant, circumstances that challenge vital physiology, most likely during sleep, at a particular developmental period.

Animals↗

Unsafe sleep practices and an analysis of bedsharing among infants dying suddenly and unexpectedly: results of a four-year, population-based, death-scene investigation study of sudden infant death syndrome and related deaths.

BACKGROUND: Prone sleep and unsafe sleep surfaces increase the risk of sudden infant death. Recent epidemiologic studies also suggest that when an infant's head or face is covered by bedding, or when a sleep surface is shared with others, the risk of dying increases. The inference of a causal role for these risk factors is supported by physiologic studies and by the consistent finding that fewer infants die when risk factors are reduced. The prevalence of most of these risk factors in infant deaths in the United States is uncertain. OBJECTIVE: To describe the prevalence of several important risk factors related to sleep practices among a defined population of infants dying suddenly and unexpectedly. METHODS: In this population-based study, we retrospectively reviewed death-scene information and medical examiners' investigations of deaths in the city of St Louis and St Louis County between January 1, 1994 and December 31, 1997. Because of the potential for diagnostic overlap, all deaths involving infants <2 years old with the diagnoses of sudden infant death syndrome (SIDS), accidental suffocation, or cause undetermined were included. RESULTS: The deaths of 119 infants were studied. Their mean age was 109.3 days (range: 6-350). The diagnoses were SIDS in 88 deaths, accidental suffocation in 16, and undetermined in 15. Infants were found prone in 61.1% of cases and were found on a sleep surface not designed for infants in 75.9%. The head or face was covered by bedding in 29.4%. A shared sleep surface was the site of death in 47.1%. Only 8.4% of deaths involved infants found nonprone and alone, with head and face uncovered. CONCLUSIONS: Using detailed death-scene descriptions, we found that similar unsafe sleeping practices occurred in the large majority of cases diagnosed as SIDS, accidental suffocation, and cause undetermined. Considering these diagnoses together may be useful in public health campaigns during a time when there may be diagnostic overlap. Regardless of the diagnosis, recommendations that infants sleep supine on firm sleep surfaces that lessen the risk of entrapment or head covering have the potential to save many lives. Campaigns are needed to heighten awareness of these messages and of the risks of dangerous bedsharing.

Asphyxia↗

Habituation of the infant arousal response.

STUDY OBJECTIVES: Arousal is considered to be an important protective response in a sleeping infant and its depression could leave an infant vulnerable to a life threatening stimulus. We found previously that arousal to a non-respiratory (tactile) stimulus occurs in a sequence of events that begins with spinal, followed by brainstem responses, and then a cortical electroencephalographic (EEG) arousal response. We hypothesized that repeated stimuli would depress the arousal responses by habituation and that spinal and brainstem responses would be more resistant to habituation than cortical responses. PARTICIPANTS: We studied 22 normal infants. INTERVENTIONS: The infants underwent polysomnographic monitoring during a daytime nap. Tactile stimuli was applied to the infants foot at 5-second intervals. MEASUREMENTS AND RESULTS: We found that spinal, brainstem, and cortical responses occurred on the first trial of each test. Repeated trials during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep resulted in a decrease in the incidence of each individual response and eventually elimination of the arousal responses. Cortical responses were eliminated first, followed by brainstem responses and finally spinal responses. The elimination of each of the responses occurred more rapidly during REM sleep that during NREM sleep. CONCLUSIONS: Habituation of the infant arousal sequence occurs with repeated tactile stimulation. There is a serial habituation of responses from the cortical to the spinal level, which occurs more rapidly during REM sleep. Rapid habituation to innocuous stimuli is probably beneficial in avoiding detrimental sleep disruptions. However, in situations requiring the protective functions of arousal, such habituation could be detrimental to an infant.

Arousal↗

Changing infants' sleep position increases risk of sudden infant death syndrome. New Zealand Cot Death Study.

OBJECTIVE: To examine whether the prone sleeping position may increase the risk for sudden infant death syndrome (SIDS), particularly in infants unused to prone sleep. DESIGN: A 3-year (1987-1990) case-control study. SETTING: Nationwide study in New Zealand. SUBJECTS: Four hundred eighty-five infants who died of SIDS and 1800 controls. MAIN OUTCOME MEASURES: Infants were classified as unaccustomed to prone if their usual sleep position was nonprone and they were placed prone for the last sleep. Secondary prone was used to describe infants placed nonprone but found prone. RESULTS: Infants usually and last placed nonprone were at the lowest risk for SIDS (odds ratio [OR], 1.0); those usually and last placed prone were at increased risk (adjusted OR, 4.6; 95% confidence interval, 3.4-6.3). Risk was greatly increased among infants unaccustomed to the prone position (adjusted OR, 19.3; 95% confidence interval, 8.2-44.8). These infants accounted for 8% (31/ 386) of all SIDS deaths. Ninety percent (28/ 31) of infants in this group were found prone, and 71% (20/28) of those found prone were found with their faces turned down into bedding-a position in which asphyxia has been implicated as a mechanism of death. In addition, 138 infants who died of SIDS were last placed nonprone. Forty-seven infants (34%) in this group were found prone (secondary prone), and 60% (28/47) of those found prone were found with their faces turned down into the bedding. This group accounted for 12% of all SIDS deaths. Most of these infants (91% [43/47]) were usually placed nonprone. CONCLUSIONS: Infants placed supine to sleep were at the lowest risk of SIDS, which supports the recommendation that this is the preferred sleeping position for healthy infants. In New Zealand, 20% of SIDS deaths involved lack of experience with the prone sleeping position. Our findings suggest the possibility that an infant's competence in escaping from potentially lethal situations during prone sleep (eg, the face-down position) may be impaired by inexperience in prone sleeping. Great caution should be exercised in placing infants unaccustomed to the prone sleeping position in the prone position.

Case-Control Studies↗

Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation.

"Autoresuscitation" (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.

Age Factors↗

Feeding responses to free-flow formula in term and preterm infants.

OBJECTIVES: Although introducing freely flowing formula into the infant's mouth is a common feeding practice, its effect on feeding behavior is largely unknown. We evaluated the effects of free flow of formula from the nipple on infant feeding activity (sucking, swallowing, ingestion rate) and documented potential adverse behaviors such as cough, restless behavior, drooling, apnea, and bradycardia. METHODS: We studied 13 preterm and 7 term infants. During a feeding, bottle pressure was adjusted every 2 to 3 minutes to increase or decrease free flow from the nipple. RESULTS: Increase in free flow of formula from the nipple caused rapid increases in suck and swallow frequency in term and preterm infants and increased ingestion rate. The response was reversed by decreasing flow and was repeatable throughout the feeding. Peak suck and swallow rates were highest in term infants. Although drooling increased with increased milk flow, no effect of flow on coughing, restless behavior, or apnea was observed. CONCLUSIONS: Free-flow formula is a potent stimulus for feeding activity in both preterm and term infants and is not associated with increased apnea or other adverse behaviors. The ability of the infant to divert excess formula flow by drooling is an efficient airway protective behavior. Reduced maximum suck and swallow frequency may be a primary basis for slow feeding in preterm infants.

Bottle Feeding↗

Characteristics of the infant arousal response.

Arousal is considered to be an important response to a life-threatening stimulus. Recently, it has been shown that the infant arousal response to an elevated inspired CO2 level occurs as a sequence of events involving presumptive brain stem responses before awakening (A. Lijowska, N. Reed, B. Chiodini, and B. T. Thach. Am. J. Respir. Crit. Care Med. 151: A151, 1995; A. S. Lijowska, N. W. Reed, B. A. Mertins Chiodini, and B. T. Thach. J. Appl. Physiol. 83: 219-228, 1997). We wanted to further evaluate the relationship of subcortical reflexes to cortical arousal in infants. We used a nonrespiratory (tactile) stimulus to elicit arousal in infants during non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. We found that a tactile stimulus elicited an arousal sequence that commenced with a spinal withdrawal reflex, was followed by brain stem responses (respiratory and startle responses), and ended in a cortical arousal. The entire pathway or part of it in the order of spinal to cortical responses could be elicited. REM and NREM responses were similar except for significant differences in the latencies of spinal and subcortical reflexes. These observations suggest that the infant arousal response to a tactile stimulus involves a progression of central nervous system activation from the spinal to cortical levels. The different components of the arousal pathway may be important for an infant to respond appropriately to stimuli during sleep without necessarily disturbing sleep.

Arousal↗

Suppression of sigma spindle electroencephalographic activity as a measure of transient arousal after spontaneous and occlusion-evoked sighs and startles.

Defective arousal mechanisms are viewed as contributory to sleep hypopnea disorders and sudden infant death syndrome. Sighs (i.e. augmented breaths) as well as startles have not traditionally been viewed as arousal-related phenomena in infants. We hypothesized that, if sighs and startles are the initial event in a sequential arousal process, then they might be associated with specific EEG activity changes, because activation of the arousal-related ascending reticular activating system can suppress thalamus-generated sigma spindle oscillations. We studied spontaneous sighs and startles and those elicited by briefly occluding the infants face mask airway in 12 normal infants (age 10-19 wk) during non-rapid eye movement sleep. We recorded EEG (C3-P3), ECG, O2 saturation, diaphragmatic electromyography, limb electromyography, and video of the infant. The startle intensity was scored on a scale of 0 to 3 based on video recorded movements. Sleep spindle periodicity was analyzed by using a threshold over a compressed spectral band array. Spontaneous sighs and sleep startles were immediately followed by an interspindle interval prolongation from (mean +/- SEM) 8.0 +/- 0.16 s (control period) to 17.9 +/- 1.45 s after spontaneous sighs, to 23.8 +/- 1.26 s after spontaneous sighs accompanied by startles and to 26.5 +/- 1.45 s after occlusion-related sighs and startles. Furthermore, the intensity of occlusion-evoked startles was positively correlated with the interspindle interval prolongation (p < 0.01). We conclude that spontaneous as well as evoked sighs and startles are immediately followed by a transient sleep spindle suppression. This phenomenon indicates a close linkage between sighs, startles, and reticular formation-related arousal mechanisms.

Airway Obstruction↗

Reflux associated apnea in infants: evidence for a laryngeal chemoreflex.

The mucosa covering the interarytenoid space at the entrance to the larynx contains specialized nerve endings (receptors) that are stimulated when a fluid comes into contact with the mucosal surface. These receptors mediate several aspiration preventive reflex responses, which include swallowing, cessation of breathing, airway constriction or closure, and coughing. The laryngeal receptors are more sensitive to water than to saline, and therefore the combined reflex response to receptor stimulation is termed the "laryngeal chemoreflex." This reflex can be activated during regurgitation of gastric contents into the pharynx, in which case the several components of the reflex serve to prevent intrapulmonary aspiration of gastric fluid. In certain infants a hyperactive laryngeal chemoreflex may cause episodic prolonged apnea. Such reflex-mediated apnea has been implicated in several kinds of prolonged infantile apnea, including apea of prematurity, gastric regurgitation-related apnea, and apnea associated with upper respiratory infection.

Apnea↗

Sequential arousal and airway-defensive behavior of infants in asphyxial sleep environments.

Infants are prone to accidental asphyxiation. Therefore, we studied airway-defensive behaviors and their relationship to spontaneous arousal behavior in 41 healthy sleeping infants (2-26 wk old), using two protocols: 1) infant was rebreathing expired air, face covered by bedding material; and 2) infant was exposed to hypercarbia, face uncovered. Multiple measurements of respiratory and motor activities were recorded (video, polygraph). The infants' response to increasing hypercarbia consisted of four highly stereotyped behaviors: sighs (augmented breaths), startles, thrashing limb movements, and full arousal (eyes open, cry). These behaviors occurred abruptly in self-limited clusters of activity and always in the same sequence: first a sigh coupled with a startle, then thrashing, then full arousal. Incomplete sequences (initial behaviors only) occurred far more frequently than the complete sequence and were variably effective in removing the bedding covering the airway. In both protocols, as inspired CO2 increased, incomplete arousal sequences recurred periodically and with increasing frequency and complexity until the infant either succeeded in clearing his/her airway or was completely aroused. Spontaneous arousal sequences, identical to those occurring during hypercarbia, occurred periodically during sleep. This observation suggests that the infant's airway-defensive responses to hypercarbia consist of an increase in the frequency and complexity of an endogenously regulated, periodically occurring sequence of arousal behaviors.

Arousal↗

Arousals in infants.

Polygraphic studies of stimulus-induced arousals from sleep in young infants have identified a highly consistent sequence of reflex responses occurring during the 2-4 second period prior to full behavioral arousal. The initial responses in this sequence are an augmented breath (sigh) coupled with a sleep startle that is then followed by stereotyped "thrashing" motor activity. Partial arousals, identified by early components of the sequence (a sigh or a sigh plus startle), were frequently elicited. Startles and thrashing activity were identified as having a significant external airway protective function during mild asphyxia induced by covering the infants' nasal and oral airways.

Arousal↗

Effects of upper airway stimulation on swallowing, gasping, and autoresuscitation in hypoxic mice.

Severe hypoxia produces a state of neural depression known as hypoxic coma in which reflex activity is believed to be absent but from which spontaneous recovery ("autoresuscitation") still can occur. We evaluated the swallowing reflex during hypoxic coma by employing mechanical and chemosensory stimuli. BALB/c mice were given 97% N2-3% CO2 to breathe. At onset of coma, a 0.05-ml bolus of saline or water was infused into the pharynx. Unlike mechanical stimulation (sham infusion), fluid infusion usually was followed by rapid swallowing, more so with water than with saline. This model allowed examination of interactions among swallowing, hypoxic gasping, airway fluid removal, and autoresuscitation. Compared with sham infusion, saline and water reduced gasping rate equally. Saline, however, prolonged the process of autoresuscitation more than did water, an effect possibly related to an observed increased retention of saline in the airway. Occasionally, mice failed to swallow after infusions, in which case airway obstruction during gasping and autoresuscitation failure was repeatedly observed. These studies suggest that the swallowing component of the laryngeal chemoreflex is present during hypoxic coma and that swallowing facilitates autoresuscitation when upper airway fluid is present.

Animals↗

Quantifying the potential of infant bedding to limit CO2 dispersal and factors affecting rebreathing in bedding.

Rebreathing may impair ventilation and lead to sudden death among sleeping infants. To estimate the potential for rebreathing imposed by an infant's sleep microenvironment, we developed a mechanical model to assess the rate of CO2 dispersal away from an infant's face. We compared the mechanical model results with changes in arterial blood gases of rabbits. The rabbits breathed into the same microenvironments used for the model studies. In the rabbits, rebreathing (documented by capnometry) caused hypercarbia and in some cases death. The mechanical model consisted of the mannequin head positioned as in the rabbit studies and connected to a 100-ml syringe filled with CO2. CO2 was washed out of the system using 30-ml "breaths" (rate = 15/min). The half times (t1/2) for CO2 dispersal served to quantify the rebreathing potential of 16 items of bedding. The t1/2 values correlated with increments in the rabbits' arterial PCO2 (r = 0.789). The threshold for the increase in the rabbits' arterial PCO2 corresponded to t1/2 values of > or = 18.7 s; the 90% point for lethality in the rabbit model was 28.1 s. The mechanical model was also used to show the independent effects of softness and porosity of bedding on its rebreathing potential. By describing the potential for rebreathing within bedding, the mechanical model should be useful in future quantitative studies of infants' respiratory adaptation to sleep microenvironments.

Animals↗