Effect of alcohol on apnea reflexes in young lambs.

This study examined the effect of alcohol on two apnea reflexes considered to be protective mechanisms through which animals and humans preserve vital functions while they are submerged in water. The laryngeal chemoreflex and the trigeminal diving reflex were studied in unanesthetized 1- to 3-wk-old lambs. Reflex stimulation resulted in reduced ventilation or apnea, bradycardia, hypertension, and blood flow redistribution in the dive pattern. After alcohol, reflex stimulation resulted in increased apnea response, preserved blood flow redistribution, but less hypertension. The onset of regular breathing following laryngeal water stimulation was significantly delayed, after alcohol, and mechanical ventilation was used in three lambs to terminate the prolonged poststimulus apnea. Airway occlusion pressure, an index of neuromuscular inspiratory drive, decreased significantly after alcohol. The study demonstrates a potent effect of alcohol on apnea reflex responses. The effect of alcohol on respiratory drive and on the apnea reflex response should be considered when humans ingest alcohol, in particular by those participating in water sports.

Vaginal disinfection with chlorhexidine during childbirth.

The purpose of this study was to determine whether chlorhexidine vaginal douching, applied by a squeeze bottle intra partum, reduced mother-to-child transmission of vaginal microorganisms including Streptococcus agalactiae (streptococcus serogroup B = GBS) and hence infectious morbidity in both mother and child. A prospective controlled study was conducted on pairs of mothers and their offspring. During the first 4 months (reference phase), the vaginal flora of women in labour was recorded and the newborns monitored. During the next 5 months (intervention phase), a trial of randomized, blinded placebo controlled douching with either 0.2% chlorhexidine or sterile saline was performed on 1130 women in vaginal labour. During childbirth, bacteria were isolated from 78% of the women. Vertical transmission of microbes occurred in 43% of the reference deliveries. In the double blind study, vaginal douching with chlorhexidine significantly reduced the vertical transmission rate from 35% (saline) to 18% (chlorhexidine), (P < 0.000 1, 95% confidence interval 0.12-0.22). The lower rate of bacteria isolated from the latter group was accompanied by a significantly reduced early infectious morbidity in the neonates (P < 0.05, 95% confidence interval 0.00-0.06). This finding was particularly pronounced in Str. agalactiae infections (P < 0.0 1). In the early postpartum period, fever in the mothers was significantly lower in the patients offered vaginal disinfection, a reduction from 7.2% in those douched using saline compared with 3.3% in those disinfected using chlorhexidine (P < 0.05, 95% confidence interval 0.01-0.06). A parallel lower occurrence of urinary tract infections was also observed, 6.2% in the saline group as compared with 3.4% in the chlorhexidine group (P < 0.01, 95% confidence p interval 0.00-0.05). This prospective controlled trial demonstrated that vaginal douching with 0.2% chlorhexidine during labour can significantly reduce both maternal and early neonatal infectious morbidity. The squeeze bottle procedure was simple, quick, and well tolerated. The beneficial effect may be ascribed both to mechanical cleansing by liquid flow and to the disinfective action of chlorhexidine.

Prematurity is associated with abnormal airway function in childhood.

To evaluate the long-term effect of prematurity and/or hyaline membrane disease (HMD) on pulmonary function and airway reactivity, we studied 49 prematurely born children aged 10 to 13 years. They were divided into three groups according to birth weight and HMD status: Groups I and II comprised the children weighing less than 1,500 g at birth, and Group III those whose birth weight exceeded 1,500 g. Children without HMD at birth were classified as Group I and those with HMD as Group II or III. We performed both pulmonary function tests and methacholine (MCh) challenges and compared the results with those of 27 age-matched controls born at term. We found that FEV1 and RV/TLC ratios were significantly different from control values in the groups with birth weights less than 1,500 g, regardless of their HMD status (Groups I and II). In Group I, results for FEF25-75%, Vmax50%, and DLCO were lower than those of controls. Airway reactivity was significantly increased in Groups I and II. A 20% drop in FEV1 after MCh challenge was found in 88%, 62%, 53%, and 36% of children in Groups I, II, and III and controls, respectively, and a 35% drop in SGaw occurred in 87%, 88%, 53%, and 59%. We conclude that prematurity and not HMD per se leads to long-term pulmonary abnormalities and to an increase in nonspecific airway reactivity.

Development of oxygen sensitivity in infants of smoking and non-smoking mothers.

AIMS: To assess the effect of prenatal cigarette smoke exposure on the postnatal resetting of oxygen sensitivity in term infants. METHODS: 15 healthy term infants of smoking mothers (median 10 cigarettes/day) and 16 controls were studied during quiet sleep 1, 3, and 10 days and 10 weeks postnatally. Strain-gauge respiratory trace was continuously recorded. Repeated 15-s challenges with 100% O2 and 15% O2 were presented in randomised order through a face mask. A median of six hyperoxic and six hypoxic challenges per recording were obtained. Breath-by-breath ventilation in a time-window from 20 s before onset of stimulus to 60 s after was extracted. For each infant at each age, the normalised coherently averaged response to hyperoxia and hypoxia was calculated. Mean ventilation at end of the 15-s stimulus was analysed with ANOVA, as were parameters describing a function fitted to each averaged response. RESULTS: During air breathing, smoke-exposed infants had higher respiratory rates and lower tidal volumes than controls. Nicotine concentration in infant hair, measured by gas chromatography, was positively correlated with maternal level of smoking. A long-term development in oxygen sensitivity was demonstrated in both groups. However, neither the time-course nor the magnitude of O2 responses was affected by maternal smoking. Overall, hyperoxia reduced ventilation by 6.3% at day 1, 13.2% at day 3, 29.6% at day 10, and 40.0% at week 10. Transient hypoxia increased ventilation by 3.5%, 3.2%, 6.4%, and 8.8%, respectively, at the four ages studied.

Traumatic head injury in infants and toddlers.

AIM: To describe the presenting characteristics, type of injury and hospital course in young children with traumatic head injury, and to identify characteristics indicating that the trauma was inflicted. METHODS: A retrospective medical record review of 91 children less than 3 years of age who were admitted to a tertiary teaching hospital in Norway from 1995 through 2005 with a traumatic head injury. Patients were identified by diagnostic codes, and categorized by type of injury as skull fractures (n = 39), epidural haemorrhage (EDH) (n = 12), subdural haemorrhage (n = 27) and parenchymal brain injury (n = 13). Further the cases were classified as inflicted injury (n = 17), accident (n = 35) or indeterminate (n = 39). RESULTS: The mechanism of injury was similar for EDHs and isolated skull fractures, and none were classified as inflicted. Sixty-three percent of the cases with subdural haematoma were classified as inflicted. When compared to the accident group, children in the inflicted group more frequently had subdural haemorrhage without a skull fracture (OR = 6.9, CI = 1.7-28.2), and seizures (OR = 9.5, CI = 2.1-43.3). CONCLUSIONS: Inflicted and accidental head injuries differed in presenting characteristics and injury type. Nearly two-third of the subdural haemorrhages were classified as inflicted, but none of the epidural EDHs or skull fractures. Inflicted injuries tended to present with seizures.

Infant sleeping position and inspiratory pressures in the upper airways and oesophagus.

Inspiratory pressures were measured at three levels in the upper airways and in the oesophagus in different sleeping positions. Thirty one consecutive healthy infants were examined at the age of 1-3 days, 25 of these at 6 weeks, and 23 at 12 weeks. Oxygen saturation, an electrocardiogram, transthoracic impedance, nasal airflow, and inspiratory pressure in the epipharynx, oropharynx, hypopharynx, and in the intrathoracic part of the oesophagus were measured. There was no significant change in the heart rate, oxygen saturation, or respiratory rate in the four sleeping positions. The peak negative inspiratory pressures obtained from the oesophagus (PES) were significantly lower in the supine head straight compared with the supine head turned and the prone positions. At 6 weeks, the only significant difference was between the supine head straight and the prone positions. The PES is less negative at all ages in the supine head straight than in all other sleeping positions, but this does not reach statistical significance.

[Ribavirin treatment of children with respiratory syncytial virus bronchiolitis]. / Ribavirinbehandling av barn med respiratorisk syncytialt virusbronkiolitt.

Until recently, the pharmacological treatment of infants with severe respiratory syncytial virus bronchiolitis has been limited to inhalation of adrenergic alfa- and beta 2-agonists, with the objective of reducing airway oedema and smooth muscle tension, thus improving oxygenation and reducing airway resistance. Corticosteroid treatment, aimed at attenuating the inflammatory response in the airway, has also been used. The introduction of the antiviral drug ribavirin, licensed in the US in 1986 and in Sweden 1989, offers a new therapeutic tool for a selected group of infants when conventional therapy proves inadequate. We report the successful treatment of a three week old infant with severe respiratory syncytial virus bronchiolitis, one of the few infants treated with ribavirin in Norway. This drug has been shown to reduce viral shedding and to improve oxygenation and clinical course. However, its cost-benefit and the safety aspects must be critically evaluated before treatment is initiated on a large scale.

Reflex apnoea response and inflammatory mediators in infants with respiratory tract infection.

The reflex apnoea response to water stimulation was evaluated in infants with respiratory syncytial virus (RSV) infection and compared to the response in non-infected infants who had sustained an apparent life-threatening event (ALTE) or were siblings of infants who had died of sudden infant death syndrome (SIDS). RSV-infected infants had a significantly (p < 0.05) reinforced reflex apnoea response compared with non-infected infants. There was a significant negative correlation between the concentration of interleukin 1 beta (IL-I beta) in pharyngeal secretions and the duration of apnoea (p < 0.01). Increased clinical severity was, however, associated with high (> 5.000 pg ml-1) concentrations of IL-1 beta. There was no correlation between apnoea and interleukin 6. These findings may be relevant for the understanding of why apnoea may be the presenting symptom of RSV infection, and offer an explanation of why a proportion of SIDS cases has a history of mild respiratory tract symptoms prior to death.

Effect of beta-adrenergic agonists on apnea reflexes in newborn lambs.

The laryngeal chemoreflex and the trigeminal diving reflex were studied in unanesthetized newborn lambs. Water stimulation of the laryngeal chemoreflex resulted in apnea, bradycardia, hypertension, and blood flow redistribution in the dive pattern. This response was significantly reduced after treatment with beta-adrenergic agonists, e.g., terbutaline. The response to laryngeal saline stimulation was not significantly altered by beta-adrenergic agonists. A similar response to trigeminal dive reflex stimulation elicited through cooling of the snout was also significantly reduced by terbutaline. Propranolol, a beta-adrenergic antagonist, reversed the terbutaline-induced effect on the laryngeal chemoreflex response. Stimulation of the superior laryngeal nerve resulted in a reflex response comparable to that from laryngeal water stimulation. The reflex response was also attenuated by terbutaline, which indicates that the action of terbutaline is not on the laryngeal chemoreceptors. A possible direct effect from beta-adrenergic agonists on the respiratory center is suggested by a latency of 15-30 min before the reflex response was reduced after intravenous but not intrathecal administration. An effect of terbutaline via the arterial chemoreceptors is also possible.

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.

Increased survival rate in very low birth weight infants (1500 grams or less): no association with increased incidence of handicaps.

The incidence of major handicaps was studied in a selected high-risk population of 1919 very low birth weight (less than or equal to 1500 gm) infants born between 1976 and 1985. Seventy-four percent of these infants were discharged alive. We have handicap information on 632 infants who have been followed for up to 7 years of age; 462 were evaluated at 18 months or later. Patients lost to follow-up represent 55% of the eligible population, but inpatient morbidity factors were available for the entire population and were used to calculate synthetic estimates of handicap rates. The overall incidence of severe major handicaps at 18 months was 18.0% (83/462). Cerebral palsy was found in 7.6%, and 6.5% were mentally retarded (IQ less than or equal to 70). Severe retinopathy of prematurity was present in 5.5%, and 5.4% of the infants had neurosensory hearing loss. Thirty-one infants (6.7%) had more than one handicap, the most common combination being cerebral palsy and mental retardation. Outcome of infants grouped by 250 gm birth weight intervals was compared for two periods (1976 to 1980, and 1981 to 1985); the numbers of survivors in each birth weight group increased during the second period, especially in the 500 to 750 gm and the 751 to 1000 gm groups. The observed incidence of major handicaps decreased from the first 5-year period to the second 5-year period (p less than 0.001). The largest decreases in the observed proportion handicapped occurred in the two lowest birth weight groups. The incidence of multiple handicaps also dropped; again, the two lowest birth weight groups showed the largest decrease. We conclude that an increased survival rate of very low birth weight infants need not be associated with an increased incidence of major handicaps.

Prolonged hypoxemia enhances and acute hypoxemia attenuates laryngeal reflex apnea in young lambs.

To determine the influence of an altered carotid body function on the laryngeal chemoreflex (LCR) response, reflex apnea was induced by laryngeal water stimulation during normoxia or acute hypoxia in unanesthetized awake lambs in which the ventilatory response to acute hypoxia was attenuated by prolonged postnatal hypoxemia. Prolonged hypoxemia (H) was induced in seven lambs for 12 d after birth through exposure to 0.10 fraction of inspired oxygen. Five control lambs were kept in 0.21 fraction of inspired oxygen. Studies were performed repeatedly during the first 7 wk after birth. The ventilatory response to LCR stimulation, expressed as a percent decrease in minute ventilation, was tested in 0.21, 0.14, and 0.10 fraction of inspired oxygen. H after birth resulted in a markedly increased inhibition of ventilation in response to LCR stimulation and postponed the age-related decrease in LCR response. A potential failure to recover from apnea occurred only in the H lambs, and in these lambs there was a significantly greater requirement for mechanical ventilation after LCR stimulation. Acute hypoxemia preceding LCR stimulation significantly attenuated the ventilatory response in both control and H lambs, with a stronger effect in the H lambs. There was no difference between the two groups in heart rate response to LCR stimulation. Acute hypoxemia significantly augmented reflex bradycardia in the H lambs. These results show that there is a relationship between H immediately after birth--which is known to delay resetting of carotid chemoreceptors--and augmented ventilatory inhibition in response to LCR stimulation. They do not confirm the theory that acute hypoxia reinforces reflex apnea.

Long-lasting effect of prolonged hypoxemia after birth on the immediate ventilatory response to changes in arterial partial pressure of oxygen in young lambs.

The effect of prolonged hypoxemia (H) after birth on the evolution of the ventilatory response to changes in arterial partial pressure of O2 was determined in unanesthetized, awake lambs. H was induced for 12 d after birth in seven lambs through exposure to 0.10 fraction of inspired O2 (FiO2). Five control (C) lambs were kept in 0.21 FiO2. The ventilatory response (percent increase from baseline) to acute hypoxia was tested with 0.14 FiO2 and 0.10 FiO2. The tonic activity of the peripheral chemoreceptors was assessed by the transient pure oxygen inhalation test (Dejours' test). The occlusion technique was used to measure the baseline neuromuscular drive of breathing. A markedly decreased early ventilatory response to acute hypoxia persisted in the H lambs for at least 5 wk after termination of H compared with the C group. The second phase of the response was significantly lower only at 12 d (the end of H) and was thereafter comparable to that in the C lambs. The ventilatory response to hyperoxia was significantly lower in the H lambs only at the end of hypoxemia at 12 d and rapidly normalized after return to normoxia. H did not significantly affect resting neuromuscular drive. These results show that postnatal maturation of the ventilatory response to changes in arterial partial pressure of O2 can be delayed by prolonged postnatal hypoxemia. The effect on the response to hyperoxia is transient, whereas the response to acute hypoxia is affected for an extended time. This study illustrates the importance of an adequate postnatal arterial partial pressure of O2 for the development of the ventilatory response to acute hypoxia.

Respiratory syncytial virus infection reinforces reflex apnea in young lambs.

To evaluate the effect of respiratory syncytial virus (RSV) infection on reflex apnea elicited by application of water on the laryngeal mucosa, 11 healthy, term lambs were chronically instrumented at 2 wk of age. Six lambs were inoculated with bovine RSV, and five lambs were mock-infected. The lambs were studied awake and unsedated before and 4, 8, 14, and 21 d after infection. RSV infection was associated with slight rhinorrhea and with moderately increased tracheal mucous discharge. There was an average increase of 0.5 degrees C in body temperature. Arterial pH, PO2, and PCO2 remained within the normal range. The ventilatory response to laryngeal chemostimulation measured as the percentage of decrease in ventilation from control was significantly (p less than 0.05) larger among the infected animals when compared with controls on d 4 and 8. There were no differences in indices of respiratory drive (airway occlusion pressure and mean inspiratory flow), ventilatory response to hypoxia (0.10 fraction of inspired O2), or hypercarbia (0.03 fraction of inspired O2). We speculate that RSV infection alters the sensitivity of the laryngeal chemoreceptors so that a prolonged or even fatal apnea may result from stimulation of these receptors. These results may be relevant to the pathogenesis of sudden infant death syndrome associated with RSV infection.

The cardiovascular response to laryngeal water administration in young lambs.

The cardiovascular response to administration of water to the larynx was studied in unanesthetized newborn lambs. The cardiovascular components of this laryngeal reflex response consisted of a decrease in heart rate associated with a decrease in cardiac output, an increase in systemic and pulmonary vascular resistance associated with increased blood pressure and blood flow redistribution. Blood flow decreased in carcass, kidneys, intestines, liver and spleen and increased in head, brain and heart. The magnitude of the separate components of the cardiovascular response correlated significantly with each other and with the respiratory response. Alpha-adrenergic blockade eliminated the blood pressure and blood flow redistribution response. Atropine blocked the heart rate response. The reflex-elicited decrease in cardiac output and the increase in systemic vascular resistance were augmented by beta-adrenergic blockade. The cardiovascular responses were diminished, but not abolished, when oxygenation and rhythmic ventilation were artificially maintained during laryngeal water stimulation. These results indicate the possible interaction with the arterial chemoreceptors, stimulated by the concomitant 26 torr decrease in arterial oxygen tension, as well as with the cessation of the pulmonary inflation reflex associated with the apnoea.

Detection of intraventricular hemorrhage (IVH) by transcephalic impedance (TCZ) in premature infants.

Transcephalic impedance was measured serially in 45 preterm infants less than 1500 g birth weight in order to test the method for the early detection of intraventricular hemorrhage. TCZ increased in all seventeen (38%) infants who developed IVH diagnosed by CT-scan or autopsy. Five of 8 infants monitored 4-8 weeks following confirmed IVH developed hydrocephalus documented by repeat CT-scans; all 5 were discovered early by the TCZ-method 2-3 weeks before physical findings or an increasing head circumference indicated the possibility of hydrocephalus. TCZ appears to be a useful non-invasive clinical guide to the occurrence and course of IVH in the newborn.

A method of assessing ventilatory responses to chemoreceptor stimulation in infants.

Various methods of assessing infant chemoreceptor responses have been reported in the literature. However, equipment dead space, trigeminal stimulation and inherent respiratory variability may have affected the results. A method is presented which attempts to reduce the effect of these factors and thereby isolate the chemoreceptor response. Inspiratory gas was delivered into a lightweight face mask with a pliable rim, minimal dead space and a connected pneumotachograph. Ventilatory data were computed breath by breath. Computer-controlled electromagnetic valves allowed instantaneous switching between air and different gas mixtures, repeated in a randomized sequence. In 18 healthy term neonates, the mask increased ventilation by 12% (95% confidence interval 6-18%), measured by calibrated strain-gauge bands. The effect on respiratory frequency and tidal volume differed significantly between sleep states. Neonates were challenged with short-lasting hyperoxia, mild hypoxia, rebreathing and mild hypercapnia. Coherent averaging of several ventilatory responses from each sleep state reduced the variability while maintaining a high time-resolution.