Showing papers on "Hypoventilation published in 2019"

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Abstract: Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Sleep in chronic respiratory disease: COPD and hypoventilation disorders.

Abstract: COPD and obstructive sleep apnoea (OSA) are highly prevalent and different clinical COPD phenotypes that influence the likelihood of comorbid OSA. The increased lung volumes and low body mass index (BMI) associated with the predominant emphysema phenotype protects against OSA whereas the peripheral oedema and higher BMI often associated with the predominant chronic bronchitis phenotype promote OSA. The diagnosis of OSA in COPD patients requires clinical awareness and screening questionnaires which may help identify patients for overnight study. Management of OSA-COPD overlap patients differs from COPD alone and the survival of overlap patients treated with nocturnal positive airway pressure is superior to those untreated. Sleep-related hypoventilation is common in neuromuscular disease and skeletal disorders because of the effects of normal sleep on ventilation and additional challenges imposed by the underlying disorders. Hypoventilation is first seen during rapid eye movement (REM) sleep before progressing to involve non-REM sleep and wakefulness. Clinical presentation is nonspecific and daytime respiratory function measures poorly predict nocturnal hypoventilation. Monitoring of respiration and carbon dioxide levels during sleep should be incorporated in the evaluation of high-risk patient populations and treatment with noninvasive ventilation improves outcomes.

Enterovirus A71 neurologic complications and long-term sequelae

Abstract: During recent 20 years, enterovirus A71 (EV-A71) has emerged as a major concern among pediatric infectious diseases, particularly in the Asia-Pacific region. The clinical manifestations of EV-A71 include uncomplicated hand, foot, and mouth disease, herpanina or febrile illness and central nervous system (CNS) involvement such as aseptic meningitis, myoclonic jerk, polio-like syndrome, encephalitis, encephalomyelitis and cardiopulmonary failure due to severe rhombencephalitis. In follow-up studies of patients with EV-A 71 CNS infection, some still have hypoventilation and need tracheostomy with ventilator support, some have dysphagia and need nasogastric tube or gastrostomy feeding, some have limb weakness/astrophy, cerebellar dysfunction, neurodevelopmental delay, lower cognition, or attention deficiency hyperactivity disorder. Long term sequelae may be related to greater severity of CNS involvement or neuron damage, hypoxia and younger age of onset.

Intranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity

Abstract: Rationale: Leptin treats upper airway obstruction and alveolar hypoventilation in leptin-deficient ob/ob mice. However, obese humans and mice with diet-induced obesity (DIO) are resistant to leptin...

Central Sleep Apnea: a Brief Review.

Abstract: The purpose of this review is to discuss the pathogenesis, clinical manifestations, diagnosis, and treatment, including areas of controversy and uncertainty. Central apnea may be due to hypoventilation or to hypocapnia following hyperventilation. The occurrence of central apnea initiates a cascade of events that perpetuates breathing instability, recurrent central apnea, and upper airway narrowing. In fact, breathing instability and upper airway narrowing are key elements of central and obstructive apnea. Clinically, central apnea is noted in association with obstructive sleep apnea, heart failure, atrial fibrillation, cerebrovascular accident tetraplegia, and chronic opioid use. Management strategies for central apnea aim to eliminate abnormal respiratory events, stabilize sleep, and alleviate the underlying clinical condition. Positive pressure therapy (PAP) remains a standard therapy for central as well as obstructive apnea. Other treatment options include adaptive servo-ventilation (ASV), supplemental oxygen, phrenic nerve stimulation, and pharmacologic therapy. However, ASV is contraindicated in patients with central sleep apnea who had heart failure with reduced ejection fraction, owing to increased mortality in this population. There are several therapeutic options for central apnea. Randomized controlled studies are needed to ascertain the long-term effectiveness of individual, or combination, treatment modalities in different types of central apnea.

Respiratory Care of Patients With Neuromuscular Disease.

Abstract: Neuromuscular diseases are a heterogeneous group of neurologic diseases that affect a number of neural structures including the motor nerves, neuromuscular junctions, or the muscles themselves. Although many of the diseases are rare, the total number of individuals who present to a pulmonologist or respiratory care provider is significant. Approaches to care include regular and careful clinical follow-up of symptoms of sleep-disordered breathing, daytime hypoventilation, as well as cough and swallowing effectiveness. Noninvasive support with nocturnal mask ventilation and a pressure support device can be extraordinarily helpful and delay daytime ventilatory failure. When daytime ventilatory failure develops, other noninvasive methods are available for portable assistance. Support of cough function with manual assistance, a resuscitator bag, and/or mechanical insufflation-exsufflation can help prevent and treat infection. Referral for swallowing evaluation and treatment is very important for those with impaired bulbar function. This comprehensive respiratory care approach to individuals with neuromuscular disease and respiratory system involvement is essential to maintaining the health and longevity of these individuals.

Anti-Hypothalamus and Anti-Pituitary Auto­antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis

Abstract: Background Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a very rare and complex pediatric syndrome characterized by altered hypothalamic thermal regulation, pain threshold, and respiratory control, hyperphagia with rapid weight gain and, often, hypothalamic-pituitary dysfunction. Its etiopathogenesis remains undetermined. We investigated the presence of alterations to target genes and hypothalamic-pituitary autoimmunity in a patient with -ROHHAD syndrome. Methods A 3-year-old girl presenting with obesity after rapid weight gain was diagnosed with ROHHAD syndrome based on clinical features and abnormal biochemical and functional testing results. Because of worsening of rapid symptoms and demonstration of oligoclonal bands on cerebrospinal fluid (CSF) analysis, she was treated with plasmapheresis, methylprednisolone, anti-CD20 monoclonal antibodies, and azathioprine. Despite initial partial clinical improvement, the patient soon died of cardiorespiratory arrest. Post-mortem, whole exome sequencing, high-resolution comparative genomic hybridization array, and optimized indirect immunofluorescence (IIF) analysis were performed on blood and CSF. Results No putative causative genomic variants compatible with dominant or recessive inheritance nor clinically significant structural rearrangement were detected. IIF on serum and CSF demonstrated the presence of anti-pituitary and anti-hypothalamus autoantibodies. Conclusions These findings support the involvement of autoimmunity in ROHHAD syndrome. However, response to immunosuppressive treatment was only transient and the patient died. Further cases are required to define the complex disease pathogenesis.

Arterial Blood Gas

Abstract: Blood gas analysis is a commonly used diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. Understanding and use of blood gas analysis enable providers to interpret respiratory, circulatory, and metabolic disorders. A "blood gas analysis" can be performed on blood obtained from anywhere in the circulatory system (artery, vein, or capillary). An arterial blood gas (ABG) tests explicitly blood taken from an artery. ABG analysis assesses a patient's partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2). PaO2 provides information on the oxygenation status, and PaCO2 offers information on the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation (rapid or deep breathing), hypoventilation (slow or shallow breathing), and acid-base status. Although oxygenation and ventilation can be assessed non-invasively via pulse oximetry and end-tidal carbon dioxide monitoring, respectively, ABG analysis is the standard. When assessing the acid-base balance, most ABG analyzers measure the pH and PaCO2 directly. A derivative of the Hasselbach equation calculates the serum bicarbonate (HCO3) and base deficit or excess. This calculation frequently results in a discrepancy from the measured due to the blood CO2 unaccounted for by the equation. The measured HCO3 uses a strong alkali that liberates all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid. The calculation only accounts for dissolved CO2; this measurement using a standard chemistry analysis will likely be called a "total CO2". For that reason, the difference will amount to around 1.2 mmol/L. However, a larger difference may be seen on the ABG, compared to the measured value, especially in critically ill patients. The calculation has been disputed as both accurate and inaccurate based on the study, machine, or calibration used and must be interpreted appropriately based on your institutional standards.Arterial blood gases are frequently ordered by emergency medicine, intensivist, anesthesiology, and pulmonology clinicians but may also be needed in other clinical settings. Many diseases are evaluated using an ABG, including acute respiratory distress syndrome (ARDS), severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, acute respiratory failure, heart failure, cardiac arrest, asthma, and inborn errors of metabolism.

Respiratory adjuncts to NIV in neuromuscular disease.

Abstract: Muscle weakness is an intrinsic feature of neuromuscular diseases (NMD). When the respiratory muscles are involved, the ability to take a deep breath is compromised, leading to reduced lung volumes and a restrictive ventilatory impairment. Inspiratory, expiratory and bulbar muscle weakness can also impair cough, which may impede secretion clearance. Non-invasive ventilation (NIV) is an established and indispensable therapy to manage hypoventilation and respiratory failure. The role of other therapies that support respiratory health is less clearly defined, and the evidence of efficacy is also harder to summarize as the underlying data are of a lesser quality. This narrative review appraises the evidence for respiratory therapies in adults with NMD and respiratory system involvement. Techniques that assist lung inflation and augment cough, such as lung volume recruitment (LVR) and mechanical insufflation-exsufflation (MI-E), are a particular focus of this review. The evidence suggests that LVR, MI-E and various combinations thereof have clinical utility generally, but important methodological limitations limit the strength of clinical recommendations and hamper the integration of evidence into practice. Future trials should prospectively assess the long-term impact of LVR and cough augmentation on clinical outcomes and burden of care in addition to lung mechanics, as well as determine clear predictors of benefit from these techniques.

Sleep-related breathing disorders in facioscapulohumeral dystrophy

Abstract: Severe manifestations of facioscapulohumeral dystrophy (FSHD) may be associated with sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and nocturnal hypoventilation (NH), but prevalence data are scarce. In patients with respiratory muscle weakness, detection of NH can be facilitated by transcutaneous capnometry, but respective data derived from FSHD patients have not yet been published. We collected sleep studies and capnometry recordings from 31 adult patients with genetically confirmed FSHD who were admitted to our sleep laboratory for first-ever evaluation of sleep-related breathing. Indications for admission included non-restorative sleep, morning headache, or excessive daytime sleepiness. In addition, sleep studies were initiated if symptoms or signs of respiratory muscle weakness were present. Thirty-one subjects with insomnia served as controls for comparison of respiratory measures during sleep. In the FSHD group, 17/31 (55%) patients showed OSA and 8 (26%) had NH. NH would have been missed in 7/8 patients if only oximetry criteria of hypoventilation had been applied. Capnography results were correlated with disease severity as reflected by the Clinical Severity Score (CSS). Non-invasive ventilation (NIV) was started in 6 patients with NH and 3 individuals with OSA. Nocturnal continuous positive airway pressure was administered to 2 patients, and positional therapy was sufficient in 4 individuals. In patients initiated on NIV, nocturnal gas exchange already improved in the first night of treatment. SDB is common in adult patients with FSHD complaining of sleep-related symptoms. It may comprise OSA, NH, and most often, the combination of both. Sleep-related hypercapnia is associated with disease severity. Transcutaneous capnometry is superior to pulse oximetry for detection of NH.

Daytime noninvasive ventilatory support for patients with ventilatory pump failure: a narrative review

Abstract: Over the past three decades, the use of noninvasive ventilation or “NIV” to assuage symptoms of hypoventilation for patients with early onset or mild ventilatory pump failure has been extended to up to the use of continuous noninvasive ventilatory support (CNVS) at full ventilatory support settings as a definitive alternative to tracheostomy mechanical ventilation. NVS, along with mechanical insufflation-exsufflation, now provides a noninvasive option for the management of both chronic and acute respiratory failure for these patients. The most common diagnoses for which these methods are useful include chest wall deformities, neuromuscular diseases, morbid obesity, high level spinal cord injury and idiopathic, primary or secondary disorders of the ventilatory control. Thus, NVS is being used in diverse settings: critical care units, medical wards, at home, and in extended care. The aim of this review is to examine the techniques used for daytime support.

Natural history of ROHHAD syndrome: development of severe insulin resistance and fatty liver disease over time

Abstract: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare syndrome with unknown etiology. Metabolic abnormalities are not known to be part of the syndrome. We present one of the oldest cases reported in the literature, who developed severe metabolic abnormalities and hepatic disease suggesting that these features may be part of the syndrome. A 27-year-old woman, diagnosed with ROHHAD syndrome at age 15, who previously developed diabetes insipidus, growth hormone deficiency, hyperprolactinemia, and hypothyroidism in her first decade of life. This was followed by insulin resistance, NAFLD, liver fibrosis, and splenomegaly before age 14 years. Her regimen included a short course of growth hormone, and cyclic estrogen and progesterone. Her metabolic deterioration continued despite treatment with metformin. Interestingly, she had a favorable response to liraglutide therapy despite having a centrally mediated cause for her obesity. At age 26, a 1.6 cm lesion was found incidentally in her liver. Liver biopsy showed hepatocellular carcinoma which was successfully treated with radiofrequency ablation. Metabolic abnormalities, Insulin resistance and fatty liver disease are potentially part of the ROHHAD syndrome that may develop over time. GLP1 agonists were reasonably effective to treat insulin resistance and hyperphagia. Patients with ROHHAD may benefit from close follow up in regards to liver disease.

Perioperative considerations in the management of obstructive sleep apnoea.

Abstract: Obstructive sleep apnoea (OSA) is characterised by repetitive compromise of the upper airway, causing impaired ventilation, sleep fragmentation, and daytime functional impairment. It is a heterogeneous condition encompassing different phenotypes. The prevalence of OSA among patients presenting for elective surgery is growing, largely attributable to an increase in age and obesity rates, and most patients remain undiagnosed and untreated at the time of surgery. This condition is an established risk factor for increased perioperative cardiopulmonary morbidity, heightened in the presence of concurrent medical comorbidities. Therefore, it is important to perform preoperative OSA screening and risk stratification - using the STOP-Bang screening questionnaire, nocturnal oximetry, and ambulatory and in-laboratory polysomnography, for example. Postoperative risk assessment is an evolving process that encompasses evaluation of upper airway compromise, ventilatory control instability, and pain-sedation mismatch. Optimal postoperative OSA management comprises continuation of regular positive airway pressure, a multimodal opioid-sparing analgesia strategy to limit respiratory depression, avoidance of supine position, and cautious intravenous fluid administration. Supplemental oxygen does not replace a patient's regular positive airway pressure therapy and should be administered cautiously to avoid risk of hypoventilation and worsening of hypercapnia. Continuous pulse oximetry monitoring with specified targets of peripheral oxygen saturation measured by pulse oximetry is encouraged.

Identifying Patients Experiencing Opioid-Induced Respiratory Depression During Recovery From Anesthesia: The Application of Electronic Monitoring Devices.

Abstract: Background Postsurgical patients experiencing opioid-related adverse drug events have 55% longer hospital stays, 47% higher costs associated with their care, 36% increased risk of 30-day readmission, and 3.4 times higher risk of inpatient mortality compared to those with no opioid-related adverse drug events. Most of the adverse events are preventable. General aim This study explored three types of electronic monitoring devices (pulse oximetry, capnography, and minute ventilation [MV]) to determine which were more effective at identifying the patient experiencing respiratory compromise and, further, to determine whether algorithms could be developed from the electronic monitoring data to aid in earlier detection of respiratory depression. Materials and methods A study was performed in the postanesthesia care unit (PACU) in an inner city. Sixty patients were recruited in the preoperative admissions department on the day of their surgery. Forty-eight of the 60 patients wore three types of electronic monitoring devices while they were recovering from back, neck, hip, or knee surgery. Machine learning models were used for the analysis. Results Twenty-four of the 48 patients exhibited sustained signs of opioid-induced respiratory depression (OIRD). Although the SpO2 values did not change, end-tidal CO2 levels increased, and MV decreased, representing hypoventilation. A machine learning model was able to predict an OIRD event 10 min before the actual event occurred with 80% accuracy. Linking evidence to action Electronic monitoring devices are currently used as a tool to assess respiratory status using thresholds to distinguish when respiratory depression has occurred. This study introduces a potential paradigm shift from a reactive approach to a proactive approach that would identify a patient at high risk for OIRD. Capnography and MV were found to be effective tools in detecting respiratory compromise in the PACU.

Noninvasive Ventilatory Support for Acute Hypercapnic Respiratory Failure.

Abstract: Noninvasive ventilation is well established as the ventilatory modality of first choice to treat acute or acute-on-chronic hypercapnic respiratory failure in patients with COPD by improving dyspnea and gas exchange, avoiding the need for intubation, and reducing morbidity and mortality rates. Noninvasive ventilation also offers benefit for patients with COPD and with accompanying pneumonia or with hypercapnic respiratory failure in postextubation, postoperative, and do not intubate settings. Noninvasive ventilation, in addition, offers benefit in other forms of acute hypercapnic respiratory failure, including those caused by asthma, cystic fibrosis, and obesity hypoventilation. A newer form of noninvasive ventilatory assistance, high-flow nasal cannula, has emerged in recent years as a technique to not only oxygenate effectively but also to improve ventilatory efficiency and reduce the work of breathing in patients with severe COPD. Results of recent studies indicate that high-flow nasal cannula therapy can benefit some patients with acute hypercapnic respiratory failure, either instead of or in combination with noninvasive ventilation, but more study is needed.

The Extremely Premature Infant (Micropremie) and Common Neonatal Emergencies

Abstract: The preterm infant, defined as birth before 37 weeks gestation, provides unique medical and surgical challenges to health care providers due to a myriad of anatomical underdevelopments and physiologic derangements. The physiology of prematurity as it relates to anesthesia is of particular importance when preparing for surgery. Anatomic differences of the premature airway and altered respiratory mechanics, such as a smaller airway diameter, increased oxygen consumption, bronchopulmonary dysplasia and apnea place these infants at risk for rapid and profound desaturation and hypoventilation during anesthesia. The immature heart has not had time to develop sufficient muscle fibers for optimal contractility. In addition, persistent pulmonary hypertension of the newborn may develop when right-to-left shunting of blood occurs through a patent ductus arteriosus and/or a patent foramen ovale due to failure of the pulmonary vascular resistance to drop at birth. These factors may combine and lead to significant cardiovascular collapse during surgery. Premature infants are susceptible to metabolic derangements such as hypoglycemia and hypocalcemia due to improper storage and loss of maternal-fetal transfer during gestation. The liver and kidneys are underdeveloped, leading to altered drug metabolism, thus, anesthetic drugs must be tailored accordingly. Neonatal surgical emergencies, such as congenital diaphragmatic hernia, hypertrophic pyloric stenosis, necrotizing enterocolitis and gastroschisis, can present at any time and be life-threatening. Immediate surgical intervention is not always necessary and there is often time for medical optimization. Advances in neonatal care have improved the morbidity and mortality of critically ill newborns.

Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations.

Abstract: Dysfunction of central respiratory CO2/H+ chemosensitivity is a pivotal factor that elicits deep hypoventilation in patients suffering from central hypoventilation syndromes. No pharmacological treatment is currently available. The progestin desogestrel has been suggested to allow recovery of respiratory response to CO2/H+ in patients suffering from central hypoventilation, but except the fact that supramedullary regions may be involved, mechanisms are still unknown. Here, we tested in neonates whether orexin systems contribute to desogestrel's central effects on respiratory function. Using isolated ex vivo central nervous system preparations from newborn rats, we show orexin and almorexant, an antagonist of orexin receptors, supressed strengthening of the increase in respiratory frequency induced by prolonged metabolic acidosis under exposure to etonogestrel, the active metabolite of desogestrel. In parallel, almorexant suppressed the increase and enhanced increase in c-fos expression in respiratory-related brainstem structures induced by etonogestrel. These results suggest orexin signalisation is a key component of acidosis reinforcement of respiratory drive by etonogestrel in neonates. Although stage of development used is different as that for progestin clinical observations, presents results provide clues about conditions under which desogestrel or etonogestrel may enhance ventilation in patients suffering from central hypoventilation syndromes.

Pulmonary hypertension and chronic hypoventilation in ROHHAD syndrome treated with average-volume assured pressure support

Abstract: Introduction: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is an exceptionally rare clinical entity with significant morbidity and high mortality with challenging-to-treat hypoventilation. Case presentation: An 11-year-old morbidly obese Chinese female presented with a putative diagnosis of ROHHAD associated with a left psoas ganglioneuroma. Initial polysomnography showed severe obstructive sleep apnea and hypoventilation. She was not adherent to prescribed non-invasive positive pressure ventilation (NIPPV). Echocardiography demonstrated evidence of pulmonary hypertension, likely secondary to chronic hypoventilation. With behavioral modification and trial of average volume-assured pressure support (AVAPS), adherence improved with eventual improvement of her pulmonary hypertension. Conclusion: AVAPS may improve ventilation and NIPPV adherence in central hypoventilation disorders such as ROHHAD, reducing risk of morbidity and mortality. Key words: Pulmonary hypertension; Hypoventilation; Positive pressure ventilation; sleep Apnea; Obstructive; Polysomnography; ROHHAD

Sequence analysis of capnography waveform abnormalities during nurse-administered procedural sedation and analgesia in the cardiac catheterization laboratory.

Abstract: Identifying common patterns in capnography waveform abnormalities and the factors that influence these patterns could yield insights to optimize responses to sedation-induced respiratory depression. Respiratory state sequences for 102 patients who had a procedure in a cardiac catheterisation laboratory with procedural sedation and analgesia were developed by classifying each second of procedures into a state of normal breathing or other capnography waveform abnormalities based on pre-specified cut-offs for respiratory rate and end-tidal CO2 concentration. Hierarchical clustering identified four common patterns in respiratory state sequences, which were characterized by a predominance of the state assigned normal breathing (n = 42; 41%), hypopneic hypoventilation (n = 38; 38%), apnea (n = 15; 15%) and bradypneic hypoventilation (n = 7; 7%). A multivariable distance matrix regression model including demographic and clinical variables explained 28% of the variation in inter-individual differences in respiratory state sequences. Obstructive sleep apnea (R2 = 2.4%; p = 0.02), smoking status (R2 = 2.8%; p = 0.01), Charlson comorbidity index score (R2 = 2.5%; p = 0.021), peak transcutaneous carbon dioxide concentration (R2 = 4.1%; p = 0.002) and receiving an intervention to support respiration (R2 = 5.6%; p = 0.001) were significant covariates but each explained only small amounts of the variation in respiratory state sequences. Oxygen desaturation (SpO2 < 90%) was rare (n = 3; 3%) and not associated with respiratory state sequence trajectories.

Chemoreflex failure and sleep-disordered breathing in familial dysautonomia: Implications for sudden death during sleep.

Abstract: Familial dysautonomia (Riley-Day syndrome, hereditary sensory and autonomic neuropathy type III) is a rare autosomal recessive disease characterized by impaired development of primary sensory and autonomic neurons resulting in a severe neurological phenotype, which includes arterial baroreflex and chemoreflex failure with high frequency of sleep-disordered breathing and sudden death during sleep. Although a rare disease, familial dysautonomia represents a unique template to study the interactions between sleep-disordered breathing and abnormal chemo- and baroreflex function. In patients with familial dysautonomia, ventilatory responses to hypercapnia are reduced, and to hypoxia are almost absent. In response to hypoxia, these patients develop paradoxical hypoventilation, hypotension, bradycardia, and potentially, death. Impaired ventilatory control due to chemoreflex failure acquires special relevance during sleep when conscious control of respiration withdraws. Overall, almost all adult (85%) and pediatric (95%) patients have some degree of sleep-disordered breathing. Obstructive apnea events are more frequent in adults, whereas central apnea events are more severe and frequent in children. The annual incidence rate of sudden death during sleep in patients with familial dysautonomia is 3.4 per 1000 person-year, compared to 0.5-1 per 1000 person-year of sudden unexpected death in epilepsy. This review summarizes recent developments in the understanding of sleep-disordered breathing in patients with familial dysautonomia, the risk factors for sudden death during sleep, and the specific interventions that could prevent it.

Sleep Complaints, Sleep and Breathing Disorders in Myotonic Dystrophy Type 2

Abstract: To update the current knowledge concerning sleep complaints and breathing disorders in myotonic dystrophy type 2 (DM2) and to better understand if sleep and breathing symptoms may add a further clinical definition of DM2. Although DM2 has been poorly evaluated, the most relevant sleep disorders are sleep-disordered breathing (SDB) (37.5–66.7%) and restless legs syndrome (RLS) (50–60%). Excessive daytime somnolence (EDS) is not consistent with SDB, and a large percentage of patients with sleep complaints (58–69%) report pain. In addition, respiratory dysfunctions are reported in 6 to 15% of DM2 patients, albeit few data are available regarding pulmonary restriction, hypoventilation, and non-invasive ventilation (NIV). SDB, RLS, and pain may contribute to sleep fragmentation and EDS in DM2. In addition, few studies report hypoventilation and pulmonary restriction, although there are no studies at all on NIV, except for limited clinical experiences. These findings suggest performing a careful pulmonary examination and NIV when required. Furthermore, sleep studies and respiratory evaluation should be recommended if OSA or respiratory muscle dysfunctions are suspected. A large polysomnographic study should be performed to clarify the link between sleep disorders, pain, and sleep disruption in DM2.

Acute Respiratory Failure in Obesity-Hypoventilation Syndrome Managed in the ICU.

Abstract: BACKGROUND: Obesity-hypoventilation syndrome (OHS) is defined as the combination of obesity (body mass index ≥ 30 kg/m2) and daytime arterial hypercapnia (PaCO2 > 45 mm Hg) in the absence of other causes of hypoventilation, and can lead to acute hypercapnic respiratory failure in the ICU. Our objective was to describe the ventilatory management and outcomes of subjects with OHS who were admitted to the ICU for acute hypercapnic respiratory failure. METHODS: We retrospectively built a cohort of subjects with OHS who were admitted for acute hypercapnic respiratory failure in 4 ICUs of the university teaching hospital in Lyon, France, between 2013 and 2017. The main end point was the rate of success of noninvasive ventilation (NIV). Secondary end points were survival from OHS diagnosis to the last follow-up and risk factors for ICU admission and long-term survival. RESULTS: One hundred fifteen subjects with OHS were included. Thirty-seven subjects (32.1%) were admitted to the ICU for acute hypercapnic respiratory failure. Congestive heart failure was the leading cause of acute hypercapnic respiratory failure (54%). At ICU admission, pH before NIV use was median (range) 7.26 (7.22–7.31) and PaCO2 was 70 (61–76) mm Hg. NIV was used as first-line ventilatory support in 36 subjects (97.2%) and was successful in 33 subjects (91.7%). ICU mortality was low (2.7%). The subjects admitted to the ICU were significantly older and had a lower FEV1 and vital capacity at the time of an OHS diagnosis. The difference in the restricted mean survival time was 663 d in favor of subjects not admitted to the ICU. Multivariate analysis showed that lower vital capacity at an OHS diagnosis was significantly associated with a higher risk of ICU admission. No factor was independently associated with long-term overall mortality in multivariate analysis. CONCLUSIONS: Acute hypercapnic respiratory failure in subjects with OHS was generally responsive to NIV and was frequently associated with congestive heart failure.

More than Heart Failure: Central Sleep Apnea and Sleep-Related Hypoventilation.

Abstract: Central sleep apnea (CSA) comprises a variety of breathing patterns and clinical entities. They can be classified into 2 categories based on the partial pressure of carbon dioxide in the arterial blood. Nonhypercapnic CSA is usually characterized by a periodic breathing pattern, while hypercapnic CSA is based on hypoventilation. The latter CSA form is associated with central nervous, neuromuscular, and rib cage disorders as well as obesity and certain medication or substance intake. In contrast, nonhypercapnic CSA is typically accompanied by an overshoot of the ventilation and often associated with heart failure, cerebrovascular diseases, and stay in high altitude. CSA and hypoventilation syndromes are often considered separately, but pathophysiological aspects frequently overlap. An integrative approach helps to recognize underlying pathophysiological mechanisms and to choose adequate therapeutic strategies. Research in the last decades improved our insights; nevertheless, diagnostic tools are not always appropriately chosen to perform comprehensive sleep studies. This supports misinterpretation and misclassification of sleep disordered breathing. The purpose of this article is to highlight unresolved problems, raise awareness for different pathophysiological components and to discuss the evidence for targeted therapeutic strategies.

Predictors of obesity hypoventilation syndrome among patients with sleep-disordered breathing in India.

Abstract: Introduction No study has been done in India to evaluate obesity hypoventilation syndrome (OHS) among patients with sleep-disordered breathing (SDB). The known predictors of OHS, i.e., body mass index (BMI) >35 kg/m2 and forced vital capacity (FVC) Objectives To find out the prevalence of OHS and to determine the predictors of OHS among Indian SDB patients. Materials and methods It was a retrospective observational study conducted in a tertiary care institute from September 1, 2017, to August 31, 2018. All the patients who underwent polysomnography were analyzed for the presence of OHS. Of 85 patients referred for polysomnography, 76 had SDB. Thirteen patients were excluded because of hypoventilation due to other known causes or could not perform spirometry. Results The prevalence of OHS among SDB after excluding the other causes of hypoventilation was 15.87% (10/63). The predictors were determined using univariate analysis between daytime partial pressure of carbon dioxide (PaCO2) and other predictors. PaCO2 significantly correlated with minimum nocturnal oxygen saturation by pulse oximetry (SpO2), FVC %predicted, BMI, daytime SpO2, forced expiratory volume %predicted, and partial pressure of oxygen (PaO2). Following a stepwise multiple regression, minimum nocturnal SpO2, FVC %predicted, and BMI were found to be independent predictors of OHS. A minimum nocturnal SpO2 threshold of 60%, FVC %predicted 30.95 kg/m2, and absolute FVC Conclusion The prevalence of OHS in Indian patients is similar to Caucasians. OHS is seen in Indian patients even at a lower BMI and lower spirometric parameters.

Obstructive Sleep Apneu (OSA), Obesitas Hypoventilation Syndrome (OHS) dan Gagal Napas

Abstract: Background: Obstructive sleep apnea (OSA) is a state of the occurrence of upper airway obstruction periodically during sleep that causes breathing to stop intermittently, either complete (apnea) or partial (hipopnea) Obesity hypoventilation syndrome (OHS) is generally defined as a combination of obesity (BMI ≥ 30 kg / mc) with arterial hypercapnia while awake (PaCO2 > 45 mmHg) in the absence of other causes of hypoventilation Purpose: In order for the pulomonologis can understand the pathogenesis and pathophysiology of OSA and its complications Literature review: Several studies have been expressed about the link between OSA, OHS with respiratory failure disease Pathophysiology of OSA, OHS in respiratory failure were difficult to detect, can cause respiratory failure disease management becomes less effective Conclusion: A good understanding can help with the diagnosis and management of the appropriate conduct to prevent complications of respiratory failure associated with OSA

Novel PHOX2B mutations in congenital central hypoventilation syndrome.

Abstract: Background Congenital central hypoventilation syndrome (CCHS) is caused by mutation of paird-like homeobox 2B (PHOX2B). Approximately 90% of patients were found to carry polyalanine repeat expansion mutation (PARM), and the remaining 10% had non-PARM (NPARM). In PARM, the length of the polyalanine expansion correlates with clinical disease severity. Most patients with NPARM have hypoventilation symptoms in the neonatal period and complications of Hirschsprung disease, dysregulation of autonomic nervous system, and tumors of neural crest origin. Data on the genotype-phenotype association may contribute to the clinical management of the disease. Methods We studied the genetic background of Japanese CCHS patients according to PHOX2B sequencing. Results Of 133 Japanese CCHS patients we identified 12 patients carrying 11 different NPARM (approx. 9% of the patients) and described the clinical manifestations in seven of them with the following novel mutations: c.941-945del5, c.678_693dup16, c.609_616del8, c.620_633del14, c.663_711del 49, c.448C>G and c.944G>C. All patients had hypoventilation in the neonatal period and also had Hirschsprung disease, with the exception of two patients carrying c.620_633del14 and c.663_711del49 mutations. The patient carrying the c.609_616del8 mutation also had a benign mediastinal tumor. Conclusion Most patients carrying NPARM had severe symptoms with frequent complications, as in previous reports, and should be carefully monitored for various complications, including neural crest-derived tumor.

Myxedema coma accompanied by sick sinus syndrome and hypoventilation: A case report.

Abstract: Myxedema coma is an emergency presentation of hypothyroidism, and cardiopulmonary manifestations of the disease are related to a high mortality rate. We herein report a case of myxedema coma accompanied by sick sinus syndrome requiring temporary cardiac pacing and hypercapnic respiratory failure in an 87-year-old woman. This case is unique because both of the cardiac and pulmonary manifestations were reversible and successfully treated with thyroid hormone replacement. Our case indicates that early detection of the condition and administration of levothyroxine are essential to improve the life-threatening condition and avoid invasive treatment such as permanent pacemaker implantation or intubation.