Onset Of Apnea Research Articles

Neonatal Nephromegaly Due to Homozygous Variant in the DIS3L2 Gene is Consistent with the Genetic Diagnosis of Perlman Syndrome

Background: Perlman syndrome is an uncommon genetic disorder grouped with overgrowth syndrome in which an abnormal increase in the size of the body or a body part of the infant often noticed at birth. The disorder, usually affects the kidneys as main findings. Perlman syndrome inherited as an autosomal recessive pattern. People with this condition are generally born with renal abnormalities also called renal hamartomas, nephroblastomatosis also been grouped with Renal cell carcinoma. The characteristic features include polyhydramnios, fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly mainly hepatomegaly and nephromegaly, dysmorphic facial features, and an increased risk for Wilms’ tumor at an early age. The prognosis of Perlman syndrome is poor with high morbidity and mortality rate. Material and Methods: We report 3 months old female infant from Saudi origin product of consanguineous marriage with prenatal sonographic signs suggestive of Perlman Syndrome specifically polyhydramnios, bilateral nephromegaly with fetal ascites. The clinical course was marked by neonatal respiratory distress, cyanosis and refractory hypoxemia with chylothorax required mechanical ventilation. Frequent hospitalization since that due to frequent attacks of apnea and chest infections. Discussion and Conclusion: The constellation of clinical presentation and radiological finding confirmed by Molecular investigations showed a homozygous variant c.1810C>T p.(Gln604*) in the DIS3L2 gene (OMIM : 614184 ) which is consistent with Autosomal Recessive Perlman syndrome.

Pre-apneic capnography waveform abnormalities during procedural sedation and analgesia.

Capnography monitoring is recommended for use during procedural sedation. This study examined associations between capnography waveform abnormalities and the onset of apnea. Capnography waveforms from a sample of 102 participants undergoing moderate procedural sedation with bolus doses of midazolam and fentanyl were analyzed using a mixed effects Cox model. Patients were at increased risk of apnea (classified as end-tidal carbon dioxide concentration of zero) while demonstrating a capnography waveform abnormality classified as hypopnea (more than 10% increase or decrease from baseline end-tidal carbon dioxide concentration) (Hazard Ratio 2.14; 95% CI 1.75 to 2.62). Risk of apnea was not increased during capnography waveform abnormalities classified as bradypnea (capnography-derived respiratory rate less than 8 breaths/min) (Hazard Ratio 0.64; 95% CI 0.33 to 1.25). These estimates were similar when apneic episodes were defined as only those that lasted more than 20 s duration. Deciphering which capnography waveform abnormalities should promote intervention (and therefore alarms to signal the event to clinicians) from those that do not is an essential step towards successful implementation of this technology into practice. Our results indicate that using information about the history of previous capnography waveform abnormalities may be a promising solution to assist prediction of apneic episodes.

Amygdala lesions reduce seizure-induced respiratory arrest in DBA/1 mice

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. Human studies and animal models suggest that respiratory arrest is the initiating event leading to death in many cases of SUDEP. It has previously been reported that the onset of apnea can coincide with the spread of seizures to the amygdala, and apnea can be reproduced by electrical stimulation of the amygdala. The aim of the current work was to determine if the amygdala is required for seizure-induced respiratory arrest (S-IRA) in a mouse model of SUDEP. Experiments were performed on DBA/1 mice that have audiogenic seizures with a high incidence of fatal postictal respiratory arrest. Electrolytic lesions of the amygdala significantly reduced the incidence of S-IRA without altering seizures, baseline breathing, or the hypercapnic ventilatory response. These results indicate that the amygdala is a critical node in a pathway to the lower brainstem that is needed for seizures to cause respiratory arrest. Significance statementSudden unexpected death in epilepsy is the most common cause of mortality in patients with refractory epilepsy, and S-IRA is thought to be important in the pathophysiology in many cases. In a patient with epilepsy, the onset of apnea has been shown to coincide with spread of seizures to the amygdala, and in multiple patients, apnea was induced by stimulation of the amygdala. Here, we show that lesions of the amygdala reduced the incidence of S-IRA and death in a mouse model of SUDEP. These results provide evidence that the amygdala may be a critical node in the pathway by which seizures influence the brainstem respiratory network to cause apnea.This article is part of the Special Issue NEWroscience 2018

Utility of a smartphone based system (cvrphone) to accurately determine apneic events from electrocardiographic signals.

BackgroundSleep disordered breathing manifested as sleep apnea (SA) is prevalent in the general population, and while it is associated with increased morbidity and mortality risk in some patient populations, it remains under-diagnosed. The objective of this study was to assess the accuracy of respiration-rate (RR) and tidal-volume (TV) estimation algorithms, from body-surface ECG signals, using a smartphone based ambulatory respiration monitoring system (cvrPhone).MethodsTwelve lead ECG signals were collected using the cvrPhone from anesthetized and mechanically ventilated swine (n = 9). During ECG data acquisition, the mechanical ventilator tidal-volume (TV) was varied from 250 to 0 to 750 to 0 to 500 to 0 to 750 ml at respiratory rates (RR) of 6 and 14 breaths/min, respectively, and the RR and TV values were estimated from the ECG signals using custom algorithms.ResultsTV estimations from any two different TV settings showed statistically significant difference (p < 0.01) regardless of the RR. RRs were estimated to be 6.1±1.1 and 14.0±0.2 breaths/min at 6 and 14 breaths/min, respectively (when 250, 500 and 750 ml TV settings were combined). During apnea, the estimated TV and RR values were 11.7±54.9 ml and 0.0±3.5 breaths/min, which were significantly different (p<0.05) than TV and RR values during non-apnea breathing. In addition, the time delay from the apnea onset to the first apnea detection was 8.6±6.7 and 7.0±3.2 seconds for TV and RR respectively.ConclusionsWe have demonstrated that apnea can reliably be detected using ECG-derived RR and TV algorithms. These results support the concept that our algorithms can be utilized to detect SA in conjunction with ECG monitoring.

The effect of seizure spread to the amygdala on respiration and onset of ictal central apnea.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death for patients with refractory epilepsy, and there is increasing evidence for a centrally mediated respiratory depression as a pathophysiological mechanism. The brain regions responsible for a seizure's inducing respiratory depression are unclear-the respiratory nuclei in the brainstem are thought to be involved, but involvement of forebrain structures is not yet understood. The aim of this study was to analyze intracranial EEGs in combination with the results of respiratory monitoring to investigate the relationship between seizure spread to specific mesial temporal brain regions and the onset of respiratory dysfunction and apnea. The authors reviewed all invasive electroencephalographic studies performed at Northwestern Memorial Hospital (Chicago) since 2010 to identify those cases in which 1) multiple mesial temporal electrodes (amygdala and hippocampal) were placed, 2) seizures were captured, and 3) patients' respiration was monitored. They identified 8 investigations meeting these criteria in patients with temporal lobe epilepsy, and these investigations yielded data on a total of 22 seizures for analysis. The onset of ictal apnea associated with each seizure was highly correlated with seizure spread to the amygdala. Onset of apnea occurred 2.7 ± 0.4 (mean ± SEM) seconds after the spread of the seizure to the amygdala, which was significantly earlier than after spread to the hippocampus (10.2 ± 0.7 seconds; p < 0.01). The findings suggest that activation of amygdalar networks is correlated with central apnea during seizures. This study builds on the authors' prior work that demonstrates a role for the amygdala in voluntary respiratory control and suggests a further role in dysfunctional breathing states seen during seizures, with implications for SUDEP pathophysiology.

Opstruktivna apneja u snu i kardiometabolički rizik

Obstructive sleep apnea (OSA) is a chronic, progressive disorder with a high prevalence in the population. Without timely diagnosis and therapy OSA can significantly affect the quality of life of the patients. OSA is a common co-morbidity in patients with metabolic syndrome (MS) and cardiovascular disease (CVD) and is an important risk factor for their development. The presence of untreated, severe OSA is associated with an increase in total and cardiovascular mortality. Numerous studies have pointed to the relationship between MS and OSA, and this phenomenon was described as syndrome Z. Investigation of the causal relationship between OSA and CVD has been greatly confounded by the complex nature of the disease itself. Cardiometabolic risk in OSA is associated with arterial hypertension, insulin resistance, endothelial dysfunction, inflammation, dyslipidemia, and oxidative stress. The treatment of OSA is now most effectively performed by continuous positive airway pressure (CPAP), a type of non-invasive ventilation which prevents the onset of sleep apnea. The results of clinical studies have shown that CPAP therapy significantly improves haemodynamic parameters, regulates hypertension, increases insulin sensitivity, and corrects dyslipidemia. Future investigations should clarify whether sleep apnea is a risk factor for CVD per se or is a consequence of a broader pathophysiological process, of which OSA is part.

Recent advances in respiratory monitory in nonoperating room anesthesia.

Sedation for nonoperating room procedures is experiencing a considerable increase in demand. Respiratory compromise is one of the most common adverse events seen in sedation. Capnography is a modality that has been widely adopted in this area, but may not be well suited to the special demands of nonoperating room sedation. This review is an assessment of new technologies that may improve outcomes beyond those achievable with capnography. New devices for detecting the onset of apnea and for assessing respiratory depression have emerged which have advantages over conventional capnography for detecting apnea without excessive false positive and false negative rates. In addition, monitors that assess respiratory drive have become available, and these may prove useful in regulating depth of sedation. No single monitor is ideal for all settings. During brief endoscopic sedation, detection of apnea is paramount, while during longer procedures, avoiding excessive respiratory depression is more critical. The clinician must choose the appropriate monitor based on an understanding of the challenges of the particular environment.

P.118 Trigemino-cardiac reflex: a case report of intra-operative asystole in response to manipulation of the temporalis muscle

Background: The trigemino-cardiac reflex (TCR) is a sudden onset of bradycardia, hypotension, apnea or gastric hypermotility during stimulation of the trigeminal nerve. Methods: We conducted a MEDLINE search for surgical cases of TCR and herein describe a case seen recently at our institution. Results: A 60 year-old female underwent a left orbitozygomatic craniotomy for resection of a skull-base tumor. Pre-operative anesthesia evaluation was unremarkable and negative for a history of cardiovascular disease. Intra-operatively, retraction with moderate force of the temporalis muscle consistently produced asystole. Cessation of retraction resulted in immediate return of sinus rhythm. Otherwise, intra-operative heart rate was 60-90 BPM. Post-operatively, vital signs and clinical course were unremarkable. The patient experienced a similar phenomenon during an operation 6 years earlier, when manipulation of tumor near cranial nerves IX/X resulted in bradycardia. TCR is the result of a polysynaptic brainstem network involving the afferent trigeminal sensory nucleus, the reticular formation, and the efferent vagal motor nucleus. Conclusions: This is a case of exaggerated vagal response following manipulation of the temporalis muscle. Our report emphasizes the importance for neurosurgeons and anesthesiologists alike to be wary of TCR in order to avoid deleterious consequences when operating on structures associated with the trigeminal nerve.

A Ballistographic Approach for Continuous and Non-Obtrusive Monitoring of Movement in Neonates.

Continuously monitoring body movement in preterm infants can have important clinical applications since changes in movement-patterns can be a significant marker for clinical deteriorations including the onset of sepsis, seizures, and apneas. This paper proposes a system and method to monitor body movement of preterm infants in a clinical environment using ballistography. The ballistographic signal (BSG) is acquired using a thin and a film-like sensor that is placed underneath an infant. Manual annotations based on video-recordings served as a reference standard for identifying movement. We investigated the performance of multiple features, constructed from the BSG waveform, to discriminate movement from no movement based on data acquired from 10 preterm infants. Since routine cardiorespiratory monitoring is prone to movement artifacts, we also compared the application of these features on the simultaneously acquired cardiorespiratory waveforms, i.e., the electrocardiogram, the chest impedance, and the photoplethysmogram. The BSG-based-features consistently outperformed those based on the routinely acquired cardiorespiratory waveforms. The best performing BSG-based feature-the signal instability index-had a mean (standard deviation) effect size of 0.90 (0.06), as measured by the area under the receiver operating curve. The proposed system for monitoring body movement is robust to noise, non-obtrusive, and has high performance in clinical settings.

Investigating Effect of Olfactory Stimulation by Vanilla on the Rate of Apnea Attacks in Neonates with Apnea of Prematurity: A Randomized Clinical Trial

Background Apnea of prematurity (AOP) is a developmental disorder that affects the premature newborns frequently. One of the new non-drug methods for controlling apnea attacks is olfactory stimulation. The aim of this study was to determine the effect of olfactory stimulation by vanilla on the rate of apnea attacks in neonates with AOP. Materials and Methods: This study is a single-blind randomized clinical trial study. The study samples included a total of 40 premature neonates with AOP who were admitted to the neonatal Intensive care unit (NICU) of Shahid Sadoughi hospital in Yazd, Iran, in 2016 and were assigned randomly in experimental (n=20), and control (n=20) groups. The experimental group was exposed to cotton impregnated with 2ml of vanillin extractfor 24 hours. The number of apnea attacks, heart rate, and arterial oxygen saturation (SaO2) level were measured before, during and after intervention for three consecutive days. Data analysis was performed using statistical analysis in SPSS version 22.0 software. Results: The results showed that there was no significant difference between the two groups in terms of mean number of apnea attacks (p>0.05). However, there was a significant difference between in the experimental group on the first day (2.84 ± 1.25), and second day (1.63 ± 1.01) in terms of the mean number of attacks. Also, there was a significant difference between the mean heart rate and SaO2 level in both the experimental and control groups (p<0.05). Conclusion: At current study, olfactory stimulation by vanilla was not effective on reducing the number of apnea attacks in neonates with AOP.

The influence of different diets on metabolism and atherosclerosis processes-A porcine model: Blood serum, urine and tissues 1H NMR metabolomics targeted analysis.

The global epidemic of cardiovascular diseases leads to increased morbidity and mortality caused mainly by myocardial infarction and stroke. Atherosclerosis is the major pathological process behind this epidemic. We designed a novel model of atherosclerosis in swine. Briefly, the first group (11 pigs) received normal pig feed (balanced diet group—BDG) for 12 months, the second group (9 pigs) was fed a Western high-calorie diet (unbalanced diet group—UDG) for 12 months, the third group (8 pigs) received a Western type high-calorie diet for 9 months later replaced by a normal diet for 3 months (regression group—RG). Clinical measurements included zoometric data, arterial blood pressure, heart rate and ultrasonographic evaluation of femoral arteries. Then, the animals were sacrificed and the blood serum, urine and skeletal muscle tissue were collected and 1H NMR based metabolomics studies with the application of fingerprinting PLS-DA and univariate analysis were done. Our results have shown that the molecular disturbances might overlap with other diseases such as onset of diabetes, sleep apnea and other obesity accompanied diseases. Moreover, we revealed that once initiated, molecular changes did not return to homeostatic equilibrium, at least for the duration of this experiment.

Sleep apnea and pesticide exposure in a study of US farmers

IntroductionCarbamate and organophosphate pesticides inhibit acetylcholinesterase, and poisoning leads to respiratory depression. Thus, involvement in sleep apnea is plausible, but no data exist at lower levels of exposure. Other pesticides could impact sleep apnea by different mechanisms but have not been studied. Our study examines the associations between pesticide exposure and sleep apnea among pesticide applicators from a US farming population. Participants and methodsWe analyzed data from 1569 male pesticide applicators, mostly farmers, from an asthma case-control study nested within the prospective Agricultural Health Study. On questionnaires, participants reported use of specific pesticides and physician diagnosis plus prescribed treatments for sleep apnea. We used multivariable logistic regression to estimate associations between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases). ResultsThe most notable association was for carbofuran, a carbamate (100 exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P=.0002). Carbofuran use began before reported onset of sleep apnea in all cases. DiscussionThis study adds to the known adverse health outcomes of exposure to carbofuran, a pesticide canceled in the United States in 2009 for most agricultural purposes but persists in the environment and remains in use in some other countries. ConclusionsWe conducted the first epidemiological study investigating the association of pesticide exposure and sleep apnea. Our results in a male agricultural population suggests that exposure to carbofuran is positively associated with sleep apnea.

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

Purpose: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model.Materials and methods: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg−1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements.Results: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration.Conclusions: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.

Investigating the effect of cardiac oscillations and deadspace gas mixing during apnea using computer simulation.

Gaseous mixing in the anatomical deadspace with stimulation of respiratory ventilation through cardiogenic oscillations is an important physiological mechanism at the onset of apnea, which has been credited with various beneficial effects, e.g. reduction of hypercapnia during the use of low flow ventilation techniques. In this paper, a novel method is proposed to investigate the effect of these mechanisms in silico. An existing computational model of cardio-pulmonary physiology is extended to include the apneic state, gas mixing within the anatomical deadspace, insufflation into the trachea and cardiogenic oscillations. The new model is validated against data published in an experimental animal (dog) study that reported an increase in arterial partial pressure of carbon dioxide (PaCO2) during apnea. Computational simulations confirm that the model outputs accurately reproduce the available experimental data. This new model can be used to investigate the physiological mechanisms underlying clearance of carbon dioxide during apnea, and hence to develop more effective ventilation strategies for apneic patients.

Low dose growth hormone treatment in infants and toddlers with Prader-Willi syndrome is comparable to higher dosage regimens

ObjectiveEvaluate benefit and risk of low dose growth hormone treatment (GHT, 4.5mg/m2/week) in very young children with Prader-Willi Syndrome (PWS). DesignProspective longitudinal clinical intervention. MethodsWe evaluated 31 infants (aged 2–12months) and 42 toddlers (13–24months) from the PWS-OZGROW database for height, weight and BMI using the World Health Organization standard deviation scores (SDSWHO) and PWS specific BMI (SDSPWS), bone age, insulin-like growth factor 1 (IGF-I) levels and adverse events over 3years of GHT. ResultsAt commencement of GHT infants had a lower BMI SDSWHO (−0.88 vs 0.40) than toddlers, while toddlers had a lower height SDSWHO (−1.44 vs −2.09) (both P<0.05). All increased height SDSWHO (2year delta height infants +1.26 SDS, toddlers+1.21 SDS), but infants normalised height sooner, achieving a height SDS of −0.56 within 1year, while toddlers achieved a height SDS of −0.88 in two years. BMI SDSWHO increased, while BMI SDSPWS decreased (both P<0.0001) and remained negative. The GHT response did not differ with gestation (preterm 23%) or genetic subtype (deletion vs maternal uniparental disomy). Bone age advancement paralleled chronological age. All children had low serum IGF-I at baseline which increased, but remained within the age-based reference range during GHT (for 81% in first year). Four children had spinal curvature at baseline; two improved, two progressed to a brace and two developed an abnormal curve over the observation period. Mild to severe central and/or obstructive sleep apnoea were observed in 40% of children prior to GHT initiation; 11% commenced GHT on positive airway pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or worsening of sleep apnoea: 2 infants in the first few months and 6 children after 6–24months. Seven resumed GHT usually after adjusting PAP but five had adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness. No other adverse events were reported. Two children substantially improved their breathing shortly after GHT initiation. ConclusionInitiation of GHT in infants with 4.5mg/m2/week was beneficial and comparable in terms of auxological response to a dose of 7mg/m2/week. Regular monitoring pre and post GH initiation assisted in early detection of adverse events. IGF-I levels increased with the lower dose but not excessively, which may lower potential long-term risks.

A prospective, randomised trial of pre-oxygenation strategies available in the pre-hospital environment.

Pre-oxygenation before tracheal intubation aims to increase safe apnoea duration by denitrogenation of the functional residual capacity of the lungs, and increasing oxygen stores at the onset of apnoea. Pre-oxygenation options in the pre-hospital environment are limited due to oxygen availability and equipment portability. The aim of this study was to evaluate the effectiveness of strategies available in this setting. This was a prospective, randomised, crossover study of 30 healthy volunteers who underwent 3-min periods of pre-oxygenation by tidal volume breathing with a non-rebreather mask, a bag-valve-mask and a portable ventilator. The primary outcome measure was fractional expired oxygen concentration of the first exhaled breath after each technique. The secondary outcome measure was ease of breathing, assessed using a visual analogue scale. The mean (95%CI) fractional expired oxygen concentrations achieved with the non-rebreather mask were 64 (60-68)%, bag-valve-mask 89 (86-92)% and portable ventilator 95 (94-96)%. Pre-oxygenation efficacy with the non-rebreather mask was significantly worse than with either the bag-valve-mask (p < 0.001) or ventilator (p < 0.001). No significant difference in ease of breathing was identified between the bag-valve-mask and ventilator, but both were perceived as being significantly more difficult to breathe through than the non-rebreather mask. We conclude that, in healthy volunteers, the effectiveness of pre-oxygenation by bag-valve-mask and portable ventilator was superior to pre-oxygenation with a non-rebreather mask, although the non-rebreather mask was easier to breathe through than the other pre-oxygenation devices.

Seizure-associated central apnea in a rat model: Evidence for resetting the respiratory rhythm and activation of the diving reflex

Respiratory derangements, including irregular, tachypnic breathing and central or obstructive apnea can be consequences of seizure activity in epilepsy patients and animal models. Periods of seizure-associated central apnea, defined as periods >1s with rapid onset and offset of no airflow during plethysmography, suggest that seizures spread to brainstem respiratory regions to disrupt breathing.We sought to characterize seizure-associated central apneic episodes as an indicator of seizure impact on the respiratory rhythm in rats anesthetized with urethane and given parenteral kainic acid to induce recurring seizures. We measured central apneic period onsets and offsets to determine if onset-offset relations were a consequence of 1) a reset of the respiratory rhythm, 2) a transient pausing of the respiratory rhythm, resuming from the pause point at the end of the apneic period, 3) a transient suppression of respiratory behavior with apnea offset predicted by a continuation of the breathing pattern preceding apnea, or 4) a random re-entry into the respiratory cycle.Animals were monitored with continuous ECG, EEG, and plethysmography. One hundred ninety central apnea episodes (1.04 to 36.18s, mean: 3.2±3.7s) were recorded during seizure activity from 7 rats with multiple apneic episodes. The majority of apneic period onsets occurred during expiration (125/161 apneic episodes, 78%). In either expiration or inspiration, apneic onsets tended to occur late in the cycle, i.e. between the time of the peak and end of expiration (82/125, 66%) or inspiration (34/36, 94%). Apneic period offsets were more uniformly distributed between early and late expiration (27%, 34%) and inspiration (16%, 23%). Differences between the respiratory phase at the onset of apnea and the corresponding offset phase varied widely, even within individual animals.Each central apneic episode was associated with a high frequency event in EEG or ECG records at onset. High frequency events that were not associated with flatline plethysmographs revealed a constant plethysmograph pattern within each animal, suggesting a clear reset of the respiratory rhythm. The respiratory rhythm became highly variable after about 1s, however, accounting for the unpredictability of the offset phase. The dissociation of respiratory rhythm reset from the cessation of airflow also suggested that central apneic periods involved activation of brainstem regions serving the diving reflex to eliminate the expression of respiratory movements. This conclusion was supported by the decreased heart rate as a function of apnea duration.We conclude that seizure-associated central apnea episodes are associated with 1) a reset of the respiratory rhythm, and 2) activation of brainstem regions serving the diving reflex to suppress respiratory behavior. The significance of these conclusions is that these details of seizure impact on brainstem circuitry represent metrics for assessing seizure spread and potentially subclassifying seizure patterns.

Nonlinear Dynamics Forecasting of Obstructive Sleep Apnea Onsets.

Recent advances in sensor technologies and predictive analytics are fueling the growth in point-of-care (POC) therapies for obstructive sleep apnea (OSA) and other sleep disorders. The effectiveness of POC therapies can be enhanced by providing personalized and real-time prediction of OSA episode onsets. Previous attempts at OSA prediction are limited to capturing the nonlinear, nonstationary dynamics of the underlying physiological processes. This paper reports an investigation into heart rate dynamics aiming to predict in real time the onsets of OSA episode before the clinical symptoms appear. A prognosis method based on a nonparametric statistical Dirichlet-Process Mixture-Gaussian-Process (DPMG) model to estimate the transition from normal states to an anomalous (apnea) state is utilized to estimate the remaining time until the onset of an impending OSA episode. The approach was tested using three datasets including (1) 20 records from 14 OSA subjects in benchmark ECG apnea databases (Physionet.org), (2) records of 10 OSA patients from the University of Dublin OSA database and (3) records of eight subjects from previous work. Validation tests suggest that the model can be used to track the time until the onset of an OSA episode with the likelihood of correctly predicting apnea onset in 1 min to 5 mins ahead is 83.6 ± 9.3%, 80 ± 8.1%, 76.2 ± 13.3%, 66.9 ± 15.4%, and 61.1 ± 16.7%, respectively. The present prognosis approach can be integrated with wearable devices, enhancing proactive treatment of OSA and real-time wearable sensor-based of sleep disorders.

Congenital Heart Disease Requiring Maintenance of Ductus Arteriosus in Critically Ill Newborns Admitted at a Tertiary Neonatal Intensive Care Unit.

Congenital heart diseases (CHD) have been reported to be responsible for 30 to 50% of infant mortality caused by congenital disabilities. In critical cases, survival of newborns with CHD depends on the patency of the ductus arteriosus (PDA), for maintaining the systemic or pulmonary circulation. The aim of the study was to assess the efficacy and side effects of PGE (prostaglandin E) administration in newborns with critical congenital heart disease requiring maintenance of the ductus arteriosus. All clinical and paraclinical data of 66 infants admitted to one referral tertiary level academic center and treated with Alprostadil were analyzed. Patients were divided into three groups: Group 1: PDA dependent pulmonary circulation (n=11) Group 2: PDA dependent systemic circulation (n=31) Group 3: PDA depending mixed circulation (n=24). The mean age of starting PGE1 treatment was 2.06 days, 1.91 (+/-1.44) days for PDA depending pulmonary flow, 2.39 (+/-1.62) days for PDA depending systemic flow and 1.71 (+/1.12) for PDA depending mixing circulation. PEG1 initiation was commenced 48 hours after admission for 72%, between 48-72 hours for 6%, and after 72 to 120 hours for 21% of newborns detected with PDA dependent circulation. Before PEG1 initiation the mean initial SpO2 was 77.89 (+/- 9.2)% and mean initial oxygen pressure (PaO2) was 26.96(+/-6.45) mmHg. At the point when stable wide open PDA was achieved their mean SpO2increased to 89.73 (+/-8.4)%, and PaO2 rose to 49 (+/-7.2) mmHg. During PGE1 treatment, eleven infants (16.7%) had apnea attacks, five children (7.5%) had convulsions, 33 (50%) had fever, 47 (71.2%) had leukocytosis, 52 (78.8%) had edema, 25.8% had gastrointestinal intolerance, 45.5% had hypokalemia, and 63.6% had irritability. For those infants with severe cyanosis or shock caused by PDA dependent heart lesions, the initiation and maintenance of PGE1 infusion is imperative. The side effects of this beneficial therapy were transient and treatable.

Characteristics of and Predictors for Apnea and Clinical Interventions During Procedural Sedation

We describe the characteristics of and predictors for apnea and clinical interventions during emergency department (ED) procedural sedation. High-resolution data were collected prospectively, using a convenience sample of ED patients undergoing propofol or ketofol sedation. End tidal CO2 (etco2), respiratory rate, pulse rate, and SpO2 were electronically recorded in 1-second intervals. Procedure times, drug delivery, and interventions were electronically annotated. Kaplan-Meier curves were used to describe the onset of clinical interventions as a function of sedation time. The onset of apnea (15 consecutive seconds with carbon dioxide ≤10 mm Hg) and clinical interventions were estimated with a series of Cox proportional hazards survival models, with time to first apnea or clinical intervention as the dependent variable. Finally, we tested the association between apnea and clinical intervention. Three hundred twelve patients were analyzed (53% male patients). Apnea was preceded by etco2 less than 30mm Hg or greater than 50 mm Hg at 30, 60, and 90 seconds before its onset. Clinical interventions were predicted by apnea, SpO2, and propofol use. Increasing age predicted both apnea and interventions. Apnea was not predicted by respiratory rate or SpO2. Apnea occurred in half of the patients and clinical interventions in a quarter of them. Clinical intervention was not predicted by abnormal respiratory rate or abnormal etco2 level. The majority of clinical interventions (85%) were minor, with no cases of assisted ventilation, intubation, or complications. Alterations in etco2 predicted apnea along a specific time course. Alterations in SpO2, apnea, and propofol use predicted clinical interventions. Increasing age predicted both apnea and clinical intervention.