Apneic Events Research Articles

Apnea of Prematurity.

Apnea of prematurity is one of the most common diagnoses in the NICU. Despite the frequency of apnea of prematurity, it is unknown whether recurrent apnea, bradycardia, and hypoxemia in preterm infants are harmful. Research into the development of respiratory control in immature animals and preterm infants has facilitated our understanding of the pathogenesis and treatment of apnea of prematurity. However, the lack of consistent definitions, monitoring practices, and consensus about clinical significance leads to significant variation in practice. The purpose of this clinical report is to review the evidence basis for the definition, epidemiology, and treatment of apnea of prematurity as well as discharge recommendations for preterm infants diagnosed with recurrent apneic events.

Stochastic Resonance Effects on Apnea, Bradycardia, and Oxygenation: A Randomized Controlled Trial.

To evaluate the effect of stochastic resonance (SR) stimulation on preterm infant oxygen desaturation, bradycardia, and apnea events. We hypothesized that SR stimulation will reduce these events. This was a randomized crossover study conducted from April 2012 to July 2014. Eligible preterm infants were not receiving ventilation support and had at least 1 clinically documented apnea, bradycardia, and/or oxygen desaturation event. The 3 outcome variables were as follows: oxygen desaturation, bradycardia, and apnea events. Infants received up to two 3- or 4-hour intervention periods of 30-minute alternating intervals of SR stimulation and no SR stimulation. The first intervention period was randomly assigned to begin with SR stimulation either on or off, whereas the next intervention period automatically began with the opposite on/off state. We compared the SR stimulation "on" periods with the SR stimulation "off" periods with each infant serving as his or her own control. The sample consisted of 36 infants with a mean (±SD) gestational age of 30.5 ± 3 weeks and a birth weight of 1409 ± 450 g. SR stimulation decreased the number of apneic events by 50%. SR stimulation ameliorated every aspect of clinically significant oxygen desaturation events, with a 20% to 35% decrease in the number, duration, and intensity of oxygen desaturation events when SR stimulation was on. Also, SR stimulation produced a nearly 20% reduction in the intensity of bradycardia events. SR stimulation may be a noninvasive and nonpharmacologic treatment option for apnea, oxygen desaturation, and some aspects of bradycardia in premature infants.

Analysis of respiratory events in obstructive sleep apnea syndrome: Inter-relations and association to simple nocturnal features

ObjectiveThis study carefully evaluates the association of different respiration-related events to each other and to simple nocturnal features in obstructive sleep apnea–hypopnea syndrome (OSAS). The events include apneas, hypopneas, respiratory event-related arousals and snores. MethodsWe conducted a statistical study on 158 adults who underwent polysomnography between July 2012 and May 2014. To monitor relevance, along with linear statistical strategies like analysis of variance and bootstrapping a correlation coefficient standard error, the non-linear method of mutual information is also applied to illuminate vague results of linear techniques. ResultsBased on normalized mutual information weights (NMIW), indices of apnea are 1.3 times more relevant to AHI values than those of hypopnea. NMIW for the number of blood oxygen desaturation below 95% is considerable (0.531). The next relevant feature is “respiratory arousals index” with NMIW of 0.501. Snore indices (0.314), and BMI (0.203) take the next place. Based on NMIW values, snoring events are nearly one-third (29.9%) more dependent to hypopneas than RERAs. Conclusion1. The more sever the OSAS is, the more frequently the apneic events happen. 2. The association of snore with hypopnea/RERA revealed which is routinely ignored in regression-based OSAS modeling. 3. The statistical dependencies of oximetry features potentially can lead to home-based screening of OSAS. 4. Poor ESS-AHI relevance in the database under study indicates its disability for the OSA diagnosis compared to oximetry. 5. Based on poor RERA-snore/ESS relevance, detailed history of the symptoms plus polysomnography is suggested for accurate diagnosis of RERAs.

Non-contact diagnostic system for sleep apnea-hypopnea syndrome based on amplitude and phase analysis of thoracic and abdominal Doppler radars.

Full-night polysomnography (PSG) has been recognized as the gold standard test for sleep apnea-hypopnea syndrome (SAHS). However, PSG examinees are physically restrained for the full night by many contact sensors and obtrusive connecting cables, inducing mental stress. We developed a non-contact SAHS diagnostic system that can detect apneic events without inducing stress in monitored individuals. Two Doppler radars were installed beneath the mattress to measure the vibrations of the chest and abdomen, respectively. Our system determines apnea and hypopnea events when the radar output amplitude decreases by <20 and 70 %, respectively, of the amplitude of a normal breath (without SAHS events). Additionally, we proposed a technique that detects paradoxical movements by focusing on phase differences between thoracic and abdominal movements, and were able to identify three types of sleep apnea: obstructive, central, and mixed. Respiratory disturbance indexes obtained showed a higher correlation (r = 94 %) with PSG than with pulse oximetry (r = 89 %). When predicting the severity of SAHS with an apnea-hypopnea index (AHI) of >15/h or >30/h using PSG as a reference, the radar system achieved a sensitivity of 96 and 90 %, and a specificity of 100 and 79 % with an AHI of >15/h and >30/h, respectively. The proposed radar system can be used as an alternative to the current airflow sensor, and to chest and abdomen belts for apnea-hypopnea evaluation.

Probabilistic cardiac and respiratory based classification of sleep and apneic events in subjects with sleep apnea

Current clinical standards to assess sleep and its disorders lack either accuracy or user-friendliness. They are therefore difficult to use in cost-effective population-wide screening or long-term objective follow-up after diagnosis. In order to fill this gap, the use of cardiac and respiratory information was evaluated for discrimination between different sleep stages, and for detection of apneic breathing. Alternative probabilistic visual representations were also presented, referred to as the hypnocorrogram and apneacorrogram. Analysis was performed on the UCD sleep apnea database, available on Physionet. The presence of apneic events proved to have a significant impact on the performance of a cardiac and respiratory based algorithm for sleep stage classification. WAKE versus SLEEP discrimination resulted in a kappa value of , while REM versus NREM resulted in and light sleep (N1N2) versus deep sleep (N3) in . The high proportion of hypopneic events led to poor detection of apneic breathing, resulting in a kappa value of . While the probabilistic representations allow to put classifier output in perspective, further improvements would be necessary to make the classifier reliable for use on patients with sleep apnea.

A gender-aware framework for the daytime detection of obstructive sleep apnea.

Sleep is an activity that is necessary for our survival. While the body may be still during sleep, the brain is actively progressing through repeating cycles of light and deep sleep whose purpose is physical and mental recovery and regeneration. Obstructive sleep apnea (OSA) is a sleep disorder in which breathing is frequently and repeatedly stopped during sleep. OSA severely interrupts the normal sleep cycle and the regeneration work associated with it and can thus result in detrimental health consequences. OSA, with all the adverse health effects associated with it, places a significant burden on the US healthcare system. Polysomnography (PSG) - the gold standard OSA diagnostic test - is an overnight sleep test that monitors the biophysiological changes that occur during sleep. The test is notorious for its intrusiveness, discomfort, prohibitive cost, and scarcity - all reasons contributing to OSA being a severely underdiagnosed sleep disorder. In this paper, we propose a system that can serve as an early-stage OSA diagnostic tool that can non-intrusively, affordably and accurately screen patients for the disorder before proceeding with a full-night PSG. Unlike existing tools, our solution is gender-aware and does not rely on detecting apneic events in the data to make a diagnosis; rather, it is designed to trigger brain responses that are indicative of the disorder. Our tool can therefore make diagnoses even while patients are awake and breathing normally. The system was tested in a pilot study of 21 patients and our preliminary results show an average accuracy of 96.25%.

Breath-by-breath detection of apneic events for OSA severity estimation using non-contact audio recordings.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder, characterized by recurrent episodes of upper airway obstructions during sleep. We hypothesize that breath-by-breath audio analysis of the respiratory cycle (i.e., inspiration and expiration phases) during sleep can reliably estimate the apnea hypopnea index (AHI), a measure of OSA severity. The AHI is calculated as the average number of apnea (A)/hypopnea (H) events per hour of sleep. Audio signals recordings of 186 adults referred to OSA diagnosis were acquired in-laboratory and at-home conditions during polysomnography and WatchPat study, respectively. A/H events were automatically segmented and classified using a binary random forest classifier. Total accuracy rate of 86.3% and an agreement of κ=42.98% were achieved in A/H event detection. Correlation of r=0.87 (r=0.74), diagnostic agreement of 76% (81.7%), and average absolute difference AHI error of 7.4 (7.8) (events/hour) were achieved in in-laboratory (at-home) conditions, respectively. Here we provide evidence that A/H events can be reliably detected at their exact time locations during sleep using non-contact audio approach. This study highlights the potential of this approach to reliably evaluate AHI in at home conditions.

Sleep apnea detection using time-delayed heart rate variability.

Sleep apnea is a sleep disorder distinguished by repetitive absence of breathing. Compared with the traditional expensive and cumbersome methods, sleep apnea diagnosis or screening with physiological information that can be easily acquired is needed. This paper describes algorithms using heart rate variability (HRV) to automatically detect sleep apneas as long as it can be easily acquired with unobtrusive sensors. Because the changes in cardiac activity are usually hysteretic than the presence of apneas with a few minutes, we propose to use the delayed HRV features to identify the episodes with sleep apneic events. This is expected to help improve the apnea detection performance. Experiments were conducted with a data set of 23 sleep apnea patients using support vector machine (SVM) classifiers and cross validations. Results show that using eleven HRV features with a time delay of 1.5 minutes rather than the features without time delay for SA detection, the overall accuracy increased from 74.9% to 76.2% and the Cohen's Kappa coefficient increased from 0.49 to 0.52. Further, an accuracy of 94.5% and a Kappa of 0.89 were achieved when applying subject-specific classifiers.

Patient position and hypoxemia during propofol sedation for colonoscopy: a randomized trial

To evaluate the benefits of the left lateral position in avoiding hypoxemic events in patients undergoing colonoscopy. We conducted a randomized, prospective, controlled trial at two study sites in Germany. Patients undergoing colonoscopy under propofol sedation were randomized to either the supine or left lateral position. The primary outcome was oxygen desaturation (SaO2<90%). Secondary outcome measures were apneic events, hypotension, patient satisfaction, propofol dosage, cecal intubation time, and adenoma detection. A total of 412 patients were randomized 1:1 to undergo colonoscopy in the supine or left lateral position. No severe adverse events were observed in either group. Intention-to-treat analysis revealed no significant difference in the frequency of desaturation in the left lateral arm compared with the supine arm (6.8% vs. 12.1%; P=0.064). Patients in the left lateral arm showed lower apnea rates (9.4% vs. 16.2%; P= .040), but had more episodes of hypotension (12.3% vs. 2.9%; P<0.001). The frequency of repositioning was higher in the left lateral group. No significant differences were observed in patient satisfaction and cooperation, propofol dosage, or adenoma detection rate. Patients who were repositioned to facilitate endoscope passage were excluded from per-protocol analysis. The incidence of hypoxemia was lower for the left lateral than for the supine group in per-protocol analysis (1.8% vs. 11.2%; P=0.003). The positioning of patients in the left lateral position during propofol sedation for colonoscopy results in lower desaturation rates provided the position can be maintained throughout endoscopy. ClinicalTrials.gov NCT02001792.

Effects of obstructive sleep apnea on hemodynamic parameters in patients entering cardiac rehabilitation.

Obstructive sleep apnea (OSA) is a prevalent form of sleep-disordered breathing. Evidence suggests that OSA may lead to cardiac remodeling, although the literature is equivocal. Previous literature suggests a high percentage of individuals entering a cardiac rehabilitation (CR) program also have OSA. The objective of this study was to determine whether resting hemodynamic variables were altered in OSA subjects entering CR compared with those without OSA, as determined by impedance cardiography. Subjects entering an early outpatient CR program were screened for OSA using an at-home screening device and verified by a sleep physician. Subjects were divided into an OSA group (n = 48) or a control group (n = 25) on the basis of the screening results. Hemodynamic variables were measured during supine rest using impedance cardiography. A 6-minute walk test was performed to assess functional capacity. The proportion of cardiac diagnoses was similar between groups. Overall, 66% of the subjects were positive for OSA. Subject groups did not differ by age, body mass index, heart rate, diastolic blood pressure, or functional capacity. Cardiac output, cardiac index, stroke volume, contractility index, and left cardiac work index were all significantly decreased in the OSA group compared with the control group (P < .05). Findings suggest that OSA results in decreased cardiac function in patients entering CR, likely because of pressure and volume changes associated with apneic events. This may place those individuals at a disadvantage in recovering from their cardiac event, and place them at increased risk for secondary complications.

The utility of the elbow sign in the diagnosis of OSA

BackgroundObstructive sleep apnea (OSA) is a common condition in which there are intermittent partial and complete limitations in airflow, with associated hypoxia and sympathetic arousals, during sleep. Many patients presenting to our sleep disorders clinic reported being elbowed or poked by their bed partner because of snoring or witnessed apneic spells. The aim of this work is to explore if a screening questionnaire can be used for detection of OSA patients. MethodsA prospective study conducted on patients referred for polysomnography in the form of questionnaire consisting of two questions: (1) Does your bed partner ever poke or elbow you because you are snoring? If yes how many times per night? (2) Does your bed partner ever poke or elbow you because you have stopped breathing? If yes how many times per night? Age, sex, weight and height were collected. ResultsSnoring event(s) and apneic event(s) were present in 47 patients, of them 40 patients had OSA (AHI ⩾5) with sensitivity: 82%, specificity: 76%, PPV: 85%, NPV: 71%. There was an increase in the patients being awakened by snoring event(s) and apneic event(s) as the disease severity increased. Age group definition (<50years) and BMI definition (⩾35kg/m2) in patients reporting snoring event(s) add a benefit as a good pretest predictor of OSA. ConclusionThe elbow sign questionnaire is a simple and quick screening tool for OSA with good sensitivity and specificity in comparison to other questionnaires, further studies are needed in other populations to determine its reliability and predictive utility.

Diagnosis of pediatric obstructive sleep apnea: Preliminary findings using automatic analysis of airflow and oximetry recordings obtained at patients’ home

The obstructive sleep apnea syndrome (OSAS) greatly affects both the health and the quality of life of children. Therefore, an early diagnosis is crucial to avoid their severe consequences. However, the standard diagnostic test (polysomnography, PSG) is time-demanding, complex, and costly. We aim at assessing a new methodology for the pediatric OSAS diagnosis to reduce these drawbacks. Airflow (AF) and oxygen saturation (SpO2) at-home recordings from 50 children were automatically processed. Information from the spectrum of AF was evaluated, as well as combined with 3% oxygen desaturation index (ODI3) through a logistic regression model. A bootstrap methodology was conducted to validate the results. OSAS significantly increased the spectral content of AF at two abnormal frequency bands below (BW1) and above (BW2) the normal respiratory range. These novel bands are consistent with the occurrence of apneic events and the posterior respiratory overexertion, respectively. The spectral information from BW1 and BW2 showed complementarity both between them and with ODI3. A logistic regression model built with 3 AF spectral features (2 from BW1 and 1 from BW2) and ODI3 achieved (mean and 95% confidence interval): 85.9% sensitivity [64.5–98.7]; 87.4% specificity [70.2–98.6]; 86.3% accuracy [74.9–95.4]; 0.947 area under the receiver-operating characteristics curve [0.826–1]; 88.4% positive predictive value [72.3–98.5]; and 85.8% negative predictive value [65.8–98.5]. The combination of the spectral information from two novel AF bands with the ODI3 from SpO2 is useful for the diagnosis of OSAS in children.

Sedation with the Combination of Ketamine and Propofol in a Pediatric ED: A Retrospective Case Series Analysis

BackgroundLiterature to date has suggested advantages of sedation with the combination of ketamine and propofol over ketamine alone or propofol alone. However, there is a paucity of data regarding sedation with the combination of ketamine and propofol in pediatric emergency medicine. MethodsA retrospective case series analysis of children who underwent sedation with the combination of ketamine and propofol in a pediatric emergency department was conducted. Study covariates were extracted from the emergency department medical records. ResultsFour hundred twenty-nine patients, 297 males and 132 females, with a median age of 6.8 years (interquartile range, 3.9-10.9 years), underwent sedation by pediatric emergency physicians. Serious adverse events during sedation (SAEDS) were recorded in 52 procedures (12.1%), which included 39 hypoxic events (9.1%), 12 apneic events (2.8%), and 1 laryngospasm (0.2%). All SAEDS were managed successfully, and no child underwent intubation because of an adverse reaction or required hospitalization. Multivariate logistic regression analysis did not reveal any association between age, weight, fasting time, analgesic medication provided before sedation, length of procedure, capnography use, dosages of medications, and the presence of SAEDS. ConclusionsThis is the largest reported series of sedation with the combination of ketamine and propofol in pediatric emergency medicine. Findings suggest that sedation with the combination of ketamine and propofol can be safely performed by a skilled emergency physician.

Abstract W P95: Disordered Breathing in a Mouse Model of Ischemic Stoke

Background: Stroke induced respiratory dysfunction is a common complication after stroke prolonging recovery and increasing mortality. Animal models are lacking. Central chemoreceptors play a vital role in regulating breathing patterns in response to changes in CO2/H+. The retrotrapezoid nucleus (RTN) in the caudal brainstem contains a population of chemoreceptors that regulate frequency and tidal volume. Activity of these neurons may be regulated by KCNQ channels. We hypothesize that targeting KCNQ channels is a viable option for the treatment of stroke induced breathing disorders. Methods: Whole body plethysmography was performed on WT C57/B6 male mice to establish baseline frequency (BPM), tidal volume (TV), minute volume (MV), periods/durations of apnea and approximate entropy of the system (ApEn). Mice were then subjected to 90 minute MCAO or sham surgery. 72 hours after surgery whole body plethysmography was performed again to identify the stroke disordered breathing phenotype. Mice were randomly assigned to one of two treatment groups: Retigabine (a KCNQ channel activator) or saline at a dose of 50ul/10g SQ, respiratory activity was monitored during a 5 day drug treatment regime. Results: All MCAO-treated mice exhibited disordered breathing characterized by pronounced decrease in respiratory frequency (254.3 ± 15.8 vs.478.2 ± 24.5 BPM) and MCAO-treated mice showed lower ApEn values compared to Sham (0.64 ± .04 vs. 1.02 ± 0.09). There was also a trend for increased number of apneic events in post-stroke animals. No significant differences were observed in TV, suggesting the respiratory phenotype observed in MCAO mice is not due to phenomena. Systemic injection of retigabine suppressed basal respiratory activity of Sham and MCAO-treated animals. Conclusions: Our results suggest that ischemic stroke results in hypoventilation and decreased respiratory stability as evidenced by a decrease in ApEn. Further, considering that retigabine worsened stroke-disordered breathing also suggests that stroke-induced respiratory problems do not result from over activation of the chemoreflex as previously proposed.

Sleep magnetic resonance imaging with electroencephalogram in obstructive sleep apnea syndrome.

To evaluate the mechanism and level of upper airway obstruction in obstructive sleep apnea (OSA) patients during natural sleep, together with synchronous electroencephalogram and respiratory events registration at 3-Tesla magnetic resonance imaging (MRI) platform with high spatial and temporal resolution. A prospective cohort study of 20 randomly selected OSA patients. Fifteen of 20 patients were able to complete spontaneous sleep during MRI. While asleep, dynamic MR images of pharynx were obtained in the midline sagittal view. During the scan, nasal and oral airflow, thoracoabdominal wall effort, and electroencephalogram were synchronously recorded. The physiologic data were retrospectively scored to identify periods of apneas and synchronized with dynamic MR images. In all 15 patients, the site of complete airway obstruction occurred at the retropalatal space. We noticed different positions of the soft palate during apneic events. In seven of 15 patients (47%), the soft palate was attached to the tongue base and moved backward, compressing the airway. In five of 15 patients (33%), the soft palate was detached from the tongue base and solely moved backward, compressing the airway. In three patients (20%), we recorded both mechanisms of complete airway obstruction. In cases with attached soft palate to the tongue base, we noticed significant narrowing of the retrolingual space during apneic events. We describe a novel mechanism of obstruction dependent on the position of soft palate. This mechanism might play an important role in selecting candidates for surgery or treatment with hypoglossal nerve stimulation. 2b.

Obstructive sleep apnea, CPAP treatment and bradyarrhythmias: close relationship or simple coincidence? A brief review based on case series

During the last decades the interest about sleep-related disordered breathing (SDB) has increased, due principally to several studies showing their involvement in cardiovascular disease. The key role of the sleep in one’s life is linked to its effects on the cardiovascular and respiratory systems. Sleep apnea syndromes (SAS) are characterized by several nightly apneic events; during these events there is the absence or a considerable reduction of the airflow with consequent oxyhemoglobin desaturation and arousal, causing microawakening and sleep fragmentation that represent, along with hypoxemia, important harmful triggers on the cardiovascular system. The impact of sleep apnea in patients with cardiovascular disease is relevant to worsen the cardiac clinical features. For the clinician it is the important to know the sleep apnea syndrome and its impact on cardiac patients regarding its negative effects; in fact, in selected patients sleep apnea should be detected, above all regarding the positive effects of its treatment.

Obstructive sleep apnea–hypopnea results in significant variations in cerebral hemodynamics detected by diffuse optical spectroscopies

The objective of this study was to adapt a novel near-infrared diffuse correlation spectroscopy (DCS) flow-oximeter for simultaneous and continuous monitoring of relative changes in cerebral blood flow (rCBF) and cerebral oxygenation (i.e. oxygenated/deoxygenated/total hemoglobin concentration: Δ[HbO2]/Δ[Hb]/ΔTHC) during overnight nocturnal polysomnography (NPSG) diagnostic test for obstructive sleep apnea–hypopnea (OSAH). A fiber-optic probe was fixed on subject’s frontal head and connected to the DCS flow-oximeter through a custom-designed fiber-optic connector, which allowed us to easily connect/detach the optical probe from the device when the subject went to bathroom. To minimize the disturbance to the subject, the DCS flow-oximeter was remotely operated by a desktop located in the control room. The results showed that apneic events caused significant variations in rCBF and ΔTHC. Moreover, the degrees of variations in all measured cerebral variables were significantly correlated with the severity of OSAH as determined by the apnea–hypopnea index (AHI), demonstrating the OSAH influence on both CBF and cerebral oxygenation. Large variations in arterial blood oxygen saturation (SaO2) were also found during OSAH. Since frequent variations/disturbances in cerebral hemodynamics may adversely impact brain function, future study will investigate the correlations between these cerebral variations and functional impairments for better understanding of OSAH pathophysiology.

Can short-term heart rate variability be used to monitor fentanyl-midazolam induced changes in ANS preceding respiratory depression?

Opioids have an occasional but high-risk side effect of respiratory depression. The detection of critical respiratory depression usually occurs after the event. Earlier detection would be beneficial in preventing increased morbidity and mortality of 0.01 % patients receiving analgesic opioids. Airway patency during inspiration requires vagal modulation. Regulation of the cardiovascular and respiratory centres may be coupled with a central mechanism that is indirectly measurable with heart rate variability (HRV). While opioids tend to increase parasympathetic tone, a decrease in airway stability could be due to a decrease in respiratory parasympathetic activity. Sympathetic arousal generated by apneic events may separately be recognised with short-term HRV. This pilot observational study examined the dynamic sympathovagal changes during fentanyl-midazolam induced respiratory depression on 10 subjects scheduled for minor surgery. A selection of HRV indices, able to work over sub-minute periods on non-stationary signals, were applied including a range of less common indices. Three analyses tested the effects: post-fentanyl, preceding the first central depression, and preceding obstruction of the upper airway. Statistical significance was assessed with overlap of bootstrap percentile confidence intervals for the median. A decrease in total variability, Lomb Total using the Lomb-Scargle method, is a positive finding for short-term HRV use in this study. No significant change before critical respiratory events was observed in traditional, spectral power, respiratory or other indices. One index, PolVar20, indicated a burst of sympathetic activity preceding respiratory depression similar to sleep apnoea arousals that restore airway patency. Before its usefulness in early detection of airway tone can be determined, PolVar20 requires further work: a statistical method for highly skewed distributions, auto adjustment for baseline variability, and detecting a range of sympathetic responses to apnea.

Risk factors for apnea in children presenting with out-of-hospital seizure.

This study aimed to quantify risk factors for apnea in children 0 to 5 years of age with out-of-hospital seizure. This is a retrospective study of pediatric patients with seizure transported by paramedics to the pediatric emergency department (PED) of a tertiary center from July 2008 to June 2009. Patients with traumatic injury and those with another diagnosis after PED evaluation were excluded. We evaluated the effect of field diazepam and other potential risk factors on the occurrence of apnea, defined as the need for airway management, that is, bag-mask ventilation by paramedics or bag-mask ventilation or intubation by PED staff within 30 minutes of arrival. There were 336 pediatric patients meeting inclusion criteria. The median age was 1.9 years (interquartile range,1.3-3.0 years); 193 patients (57%) were male. Fifty-four patients (16%) were treated with diazepam before PED arrival. There were 28 apneic events (8.3%). The adjusted relative risk for apnea given diazepam in the field by any route was 10.2 (95% confidence interval, 3.9-21.8; P < 0.0001), adjusted for age and seizure on arrival. Persistent seizure on PED arrival was also highly associated with apnea, with an adjusted relative risk of 15.8 (95% confidence interval, 6.5-28.9; P < 0.0001). Field treatment with diazepam and seizing at the time of PED arrival are associated with the occurrence of apnea in children 0 to 5 years of age with out-of-hospital seizure. Larger studies are needed to determine what other factors may contribute to this risk.

Association between gastroesophageal reflux and pathologic apneas in infants: a systematic review.

In infants, apneas can be centrally mediated, obstructive or both and have been proposed to be gastroesophageal reflux (GER) induced. Evidence for this possible association has never been systematically reviewed. To perform a systematic review using PubMed, EMBASE and Cochrane databases to determine whether an association between GER and apnea in infants exists. Studies with n ≥ 10 infants, aged <12 months, were included. GER had to be studied by pH-metry or pH-impedancemetry. GER episodes were defined as pH <4 for ≥ 5 s and/or a drop of >50% of baseline in impedance signal in distal channels. An apneic event was defined as a cessation of breathing for >20 s, or ≥ 10 s with hypoxemia or bradycardia. An epoch of ≤ 2 min was used to define temporal relation between GER and apnea. Methodological quality of studies was assessed with Newcastle Ottawa Scale (NOS). Of 1959 abstracts found, 6 articles met the inclusion criteria. All studies had poor methodological quality. A total of 289 infants were included. The temporal association of GER followed by apnea was assessed in all studies, with epochs varying from 10 s to 2 min. One study found an increase of apneic events after GER, the remaining 5 studies did not find an association. Two studies assessed apnea followed by GER as well, but did not find sufficient evidence for association. This systematic review showed insufficient evidence for an association between GER and apneas in infants. High quality studies using uniform inclusion criteria, definitions according to accepted guidelines, and patient relevant outcome measures are needed.