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Showing papers on "Hypoventilation published in 2021"


Journal ArticleDOI
TL;DR: The current knowledge of the consequences of SBDs on pulmonary haemodynamics in patients with and without chronic respiratory disease is considered and the effect of treatments of respiratory events during sleep on PH is considered.
Abstract: Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to increase pulmonary arterial pressure (PAP) during sleep but also in the waking state. "Pure" obstructive sleep apnoea syndrome (OSAS) is responsible for a small increase in PAP whose clinical impact has not been demonstrated. By contrast, in obesity hypoventilation syndrome (OHS) or overlap syndrome (the association of chronic obstructive pulmonary disease (COPD) with obstructive sleep apnoea (OSA)), nocturnal respiratory events contribute to the development of pulmonary hypertension (PH), which is often severe. In the latter circumstances, treatment of SBDs is essential in order to improve pulmonary haemodynamics.Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are at risk of developing SBDs. Obstructive and central apnoea, as well as a worsening of ventilation-perfusion mismatch, can be observed during sleep. There should be a strong suspicion of SBDs in such a patient population; however, the precise indications for sleep studies and the type of recording remain to be specified. The diagnosis of OSAS in patients with PAH or CTEPH should encourage treatment with continuous positive airway pressure (CPAP). The presence of isolated nocturnal hypoxaemia should also prompt the initiation of long-term oxygen therapy. These treatments are likely to avoid worsening of PH; however, it is prudent not to treat central apnoea and Cheyne-Stokes respiration (CSR) with adaptive servo-ventilation in patients with chronic right-heart failure because of a potential risk of serious adverse effects from such treatment.In this review we will consider the current knowledge of the consequences of SBDs on pulmonary haemodynamics in patients with and without chronic respiratory disease (group 3 of the clinical classification of PH) and the effect of treatments of respiratory events during sleep on PH. The prevalence and consequences of SBDs in PAH and CTEPH (groups 1 and 4 of the clinical classification of PH, respectively), as well as therapeutic options, will also be discussed.

44 citations


Journal ArticleDOI
TL;DR: In this article, the authors considered obesity hypoventilation syndrome (OHS) as a diagnosis in obese patients (body mass index [BMI] ≥ 30 kg/m2) who also have sleep-disordered breathing and awake diurnal hypercapnia in the absence of other causes of hypoventsilation.
Abstract: Obesity hypoventilation syndrome (OHS) is considered as a diagnosis in obese patients (body mass index [BMI] ≥30 kg/m2) who also have sleep-disordered breathing and awake diurnal hypercapnia in the absence of other causes of hypoventilation. Patients with OHS have a higher burden of medical comorbidities as compared to those with obstructive sleep apnea (OSA). This places patients with OHS at higher risk for adverse postoperative events. Obese patients and those with OSA undergoing elective noncardiac surgery are not routinely screened for OHS. Screening for OHS would require additional preoperative evaluation of morbidly obese patients with severe OSA and suspicion of hypoventilation or resting hypoxemia. Cautious selection of the type of anesthesia, use of apneic oxygenation with high-flow nasal cannula during laryngoscopy, better monitoring in the postanesthesia care unit (PACU) can help minimize adverse perioperative events. Among other risk-reduction strategies are proper patient positioning, especially during intubation and extubation, multimodal analgesia, and cautious use of postoperative supplemental oxygen.

19 citations


Journal ArticleDOI
11 Jun 2021-Sleep
TL;DR: In this article, the authors showed that Ad-LepR b infection resulted in LepR b expression in the dorsomedial hypothalamus (DMH) neurons in a similar fashion to wildtype mice.
Abstract: Study objectives Obesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin- deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin's respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepR b-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals. Methods We measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepR b or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin. Results Awake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepR b infection resulted in LepR b expression in the DMH neurons in a similar fashion to wildtype mice. In LepR b-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals. Conclusion Leptin stimulates breathing and treats obesity hypoventilation acting on LepR b-positive neurons in the DMH.

16 citations


Journal ArticleDOI
TL;DR: In this article, the authors provide a comprehensive description of the etiopathogenetic theories of the disease, clinical presentation, diagnostic workup and treatment possibilities for ROHHAD, which is characterized by precipitous obesity in young children, hypoventilation and autonomic dysregulation with various endocrine abnormalities.
Abstract: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) syndrome is a rare disease with unknown and debated etiology, characterized by precipitous obesity in young children, hypoventilation and autonomic dysregulation with various endocrine abnormalities. Neuroendocrine tumors can be associated in more than half of the cases. This rare condition has a severe outcome because of high morbidity and mortality. We provide a comprehensive description of the etiopathogenetic theories of the disease, clinical presentation, diagnostic workup and treatment possibilities.

14 citations


Journal ArticleDOI
TL;DR: In this paper, a review summarizes latest researches that improved the comprehension of the molecular pathogenetic mechanisms responsible for Congenital Central Hypoventilation syndrome and discusses the search for therapeutic intervention in light of the current knowledge about PHOX2B function.
Abstract: Congenital central hypoventilation syndrome (CCHS) is a genetic disorder of neurodevelopment, with an autosomal dominant transmission, caused by heterozygous mutations in the PHOX2B gene. CCHS is a rare disorder characterized by hypoventilation due to the failure of autonomic control of breathing. Until now no curative treatment has been found. PHOX2B is a transcription factor that plays a crucial role in the development (and maintenance) of the autonomic nervous system, and in particular the neuronal structures involved in respiratory reflexes. The underlying pathogenetic mechanism is still unclear, although studies in vivo and in CCHS patients indicate that some neuronal structures may be damaged. Moreover, in vitro experimental data suggest that transcriptional dysregulation and protein misfolding may be key pathogenic mechanisms. This review summarizes latest researches that improved the comprehension of the molecular pathogenetic mechanisms responsible for CCHS and discusses the search for therapeutic intervention in light of the current knowledge about PHOX2B function.

12 citations


Journal ArticleDOI
TL;DR: The clinical presentation of sleep‐disordered breathing and respiratory patterns at rest and during a 6‐min walk test (6MWT) in children with rapid‐onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is characterized.
Abstract: Objective To characterize the clinical presentation of sleep-disordered breathing and respiratory patterns at rest and during a 6-minute walk test (6MWT) in children with rapid-onset obesity, hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome. Methods Retrospective study of children with ROHHAD who had a diagnostic baseline polysomnography, daytime cardiorespiratory monitoring at rest and a 6MWT. Polysomnography data were also compared with BMI-, age- and sex-matched controls. Results Of the 8 children with ROHHAD, all 8 (100%) had obstructive sleep apnea (OSA) and 2/8 (25%) had nocturnal hypoventilation on their baseline polysomnography. Comparing the ROHHAD group to the control group, there were no significant differences in the median [IQR] obstructive apnea-hypopnea index (OAHI) (11.1 [4.3-58.4] vs 14.4 [10.3-23.3] events/hour, respectively; p=0.78). However, children with ROHHAD showed a significantly higher desaturation index compared to the control group (37.9 [13.7-59.8] vs 14.7 [4.3-27.6] events/hour; p=0.05). While awake at rest, some children with ROHHAD experienced significant desaturations associated with central pauses. During the 6MWT, no significant desaturations were observed, but two children showed moderate functional limitation. Conclusions Among children with ROHHAD, respiratory instability may be demonstrated by a significant number and severity of oxygen desaturations during sleep in the presence of OSA, with or without nocturnal hypoventilation, and oxygen desaturations with central pauses at rest during wakefulness. Interestingly, during daily activities that require submaximal effort, children may not experience oxygen desaturations. Early recognition of respiratory abnormalities and targeted therapeutic interventions are important to limit associated morbidity and mortality in ROHHAD. This article is protected by copyright. All rights reserved.

9 citations


Journal ArticleDOI
TL;DR: The case of a 36-month-old boy with the classic symptoms of ROHHAD and a neuroendocrine tumor, who progressed rapidly and subsequently succumbed to cardiorespiratory arrest because of hypoventilation is presented.
Abstract: Rapid onset Obesity, Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare syndrome whose underlying pathophysiology and etiology remain elusive. We present the case of a 36-month-old boy with the classic symptoms of ROHHAD and a neuroendocrine tumor, who progressed rapidly and subsequently succumbed to cardiorespiratory arrest because of hypoventilation. His magnetic resonance imaging findings at the initial diagnosis and the brain autopsy results are detailed. The literature was reviewed to summarize the current understanding of the underlying mechanism of this rare disorder.

7 citations


Journal ArticleDOI
01 Sep 2021-Breathe
TL;DR: Obesity hypoventilation syndrome is defined as daytime alveolar hypventilation in obese patients in the absence of other causes of hypovents, and classifications of severity are now needed to target treatment at the most appropriate individuals.
Abstract: With increasing prevalence of obesity, the substantial contribution of obesity hypoventilation syndrome (OHS) to morbidity and mortality is likely to increase. It is therefore crucial that the condition has a clear definition to allow timely identification of patients. OHS was first described as “Pickwickian syndrome” in the 1950s; in subsequent decades, case reports did not clearly delineate between patients suffering from OHS and those suffering from obstructive sleep apnoea. In 1999, the American Academy of Sleep Medicine published a guideline that delineated the cause of daytime hypercapnia as either predominantly upper airway or predominantly hypoventilation. This was the first formal definition of OHS as the presence of daytime alveolar hypoventilation (arterial carbon dioxide tension >45 mmHg) in patients with body mass index >30 kg·m−2 in the absence of other causes of hypoventilation. This definition is reflected in the most recent guidelines published on OHS. Recent developments in defining OHS include proposed classification systems of severity and demonstrating the value of using serum bicarbonate to exclude OHS in patients with a low index of suspicion. Educational aims To provide an overview of the historical basis of the definition of obesity hypoventilation syndrome. To explain the rationale for the current definition of obesity hypoventilation syndrome. To demonstrate areas that need further investigation in defining obesity hypoventilation syndrome.

7 citations


Journal ArticleDOI
01 Sep 2021
TL;DR: The article provides an overview of the pathogenesis, associated risk factors, prevalence, and management of sleep‐related breathing disorders in COPD, and proposes a phenotypic approach toward the diagnosis and treatment of OS and the entire spectrum of sleep-related breathing Disorders in COPd.
Abstract: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common chronic diseases. These two noncommunicable diseases (NCDs) are prevalent among approximately 10% of the general population. Approximately 1% of the population is affected by the co-existence of both conditions, known as the overlap syndrome (OS). OS patients suffer from greater degrees of nocturnal oxygen desaturation and cardiovascular consequences than those with either condition in isolation. Besides OS, patients with COPD may suffer from a spectrum of sleep-related breathing disorders, including hypoventilation and central sleep apnea. The article provides an overview of the pathogenesis, associated risk factors, prevalence, and management of sleep-related breathing disorders in COPD. It examines respiratory changes during sleep caused by COPD and OSA. It elaborates upon the factors that link the two conditions together to lead to OS. It also discusses the clinical evaluation and diagnosis of these patients. Subsequently, it reviews the pathophysiological basis and the current evidence for three potential therapies: positive airway pressure therapy [including continuous positive airway pressure (CPAP) and bilevel positive airway pressure], oxygen therapy, and pharmacological therapy. It also proposes a phenotypic approach toward the diagnosis and treatment of OS and the entire spectrum of sleep-related breathing disorders in COPD. It concludes with the current evidence gaps and future areas of research in the management of OS.

7 citations


Journal ArticleDOI
TL;DR: In this article, the acid-base status of arterial and peripheral venous blood was measured in emergency medicine patients without permanent arterial catheters, where the pain and anxiety associated with arterial punctures can cause ventilatory changes.
Abstract: ABGs are performed in acute conditions as the reference method for assessing the acid-base status of blood. Hyperventilation and breath-holding are common ventilatory changes that occur around the time of sampling, rapidly altering the ‘true’ status of the blood. This is particularly relevant in emergency medicine patients without permanent arterial catheters, where the pain and anxiety of arterial punctures can cause ventilatory changes. This study aimed to determine whether peripheral venous values could be a more reliable measure of blood gases following acute changes in ventilation. To allow for characterisation of ventilatory changes typical of acutely ill patients, but without the confounding influence of perfusion or metabolic disturbances, 30 patients scheduled for elective surgery were studied in a prospective observational study. Following anaesthesia, and before the start of the surgery, ventilator settings were altered to achieve a + 100% or − 60% change in alveolar ventilation (‘hyper-’ or ‘hypoventilation’), changes consistent with the anticipation of a painful arterial puncture commonly encountered in the emergency room. Blood samples were drawn simultaneously from indwelling arterial and peripheral venous catheters at baseline, and at 15, 30, 45, 60, 90 and 120 s following the ventilatory change. Comparisons between the timed arterial (or venous) samples were done using repeated-measures ANOVA, with post-hoc analysis using Bonferroni’s correction. Arterial blood pH and PCO2 changed rapidly within the first 15–30s after both hyper- and hypoventilation, plateauing at around 60s (∆pH = ±0.036 and ∆PCO2 = ±0.64 kPa (4.7 mmHg), respectively), with peripheral venous values remaining relatively constant until 60s, and changing minimally thereafter. Mean arterial changes were significantly different at 30s (P < 0.001) when compared to baseline, in response to both hyper- and hypoventilation. This study has shown that substantial differences in arterial and peripheral venous acid-base status can be due to acute changes in ventilation, commonly seen in the ER over the 30s necessary to sample arterial blood. If changes are transient, peripheral venous blood may provide a more reliable description of acid-base status.

5 citations


Journal ArticleDOI
TL;DR: Whether or not patients with severe OHS treated with continuous positive airway pressure remained controlled with this therapy over the long term and which variables were associated with CPAP failure and the need to switch to non-invasive ventilation (NIV) are analyzed.
Abstract: The optimal mode of long-term positive airway pressure (PAP) treatment for obesity-hypoventilation syndrome (OHS) is not clear. The objectives of this study were to analyze whether or not patients with severe OHS treated with continuous positive airway pressure (CPAP) remained controlled with this therapy over the long term and to investigate which variables were associated with CPAP failure and the need to switch to non-invasive ventilation (NIV). In a retrospective single-center study, patients admitted to the hospital because of severe OHS between 1996 and 2015 were analyzed. A multiple regression analysis was performed in order to determine which variables were associated with either CPAP success or failure to maintain long-term control. Of 126 consecutive patients, 115 accepted long-term PAP treatment. CPAP or NIV treatment was prescribed according to a protocol that included overnight polysomnographic PAP titration. Follow-up time was 8.0 ± 4.8 years. At the end of this period, 29% of CPAP-treated patients had been re-assigned to NIV because of recurrence of global respiratory failure. High levels of obesity, weight gain, lower FEV1/FVC values and the need for nocturnal supplementary oxygen independently predicted CPAP failure. CPAP therapy for severe OHS in patients who have these risk factors should be closely monitored in the long-term for possible treatment failure.

Journal ArticleDOI
TL;DR: In this article, the performance of SAT in diagnosing OSA and predicting the presence of obesity-related sleep hypoventilation (ORSH) among patients with grade III obesity without awake hypercapnia was evaluated.

Journal ArticleDOI
TL;DR: The results indicate that severe hypoventilation and HSCR are frequently observed in this group of neonatal-onset CCHS cases and molecular testing in suspicious neonates and genetic counseling for CCHs families are highly recommended.
Abstract: Background Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (PHOX2B) gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. The aim of this study is to expand current knowledge of clinical and genetic features of neonates with CCHS and provide data on the genotype-phenotype correlation. Methods We made a retrospective analysis of 14 neonates carrying PHOX2B pathogenic variants from 2014 to 2019 and we reviewed previously published neonatal-onset cases. Clinical and genetic data were analyzed. Moreover, genotype-phenotype correlation analysis was performed. Results We identified a total of 60 neonatal-onset CCHS cases (35 males and 25 females) including 14 novel cases from our local cohort. Nearly 20% (18.2%) of the patients were born prematurely. Nearly half (46.2%) of the patients had abnormal family history. Polyhydramnios was observed in 21.3% (10/47) of the patients. About 90% of the patients manifested symptoms of hypoventilation in the first week of life. Fourteen patients (23.3%) were classified as mild-CCHS and the rest were severe-CCHS. Gastrointestinal manifestations were observed in 71.7% of the patients. Approximately twofold more males than females were affected by Hirschprung disease (HSCR)/variant HSCR (75.8% vs. 35%, P=0.003). Neural crest tumor occurred in 9.1% (4/44) patients. Half patients had polyalanine repeat expansion mutations (PARMs) in PHOX2B (seven with 25 PARM, nine with 26 PARM, twelve with 27 PARM, one with 28 PARM and one with 31 PARM) and the other half patients had 23 distinct non-polyalanine repeat expansion mutations (NPARMs) with one novel pathogenic variant (c.684dup). The prevalence of HSCR and mild-CCHS among patients with NPARMs was significantly greater than that of the patients with PARMs. Conclusions This report provides a large cohort of neonatal-onset CCHS cases. The results indicate that severe hypoventilation and HSCR are frequently observed in this group. NPARMs accounted for half of the cohort with some genotypes tend to be associated with mild phenotype. Molecular testing in neonates with suspicion of CCHS and genetic counseling for CCHS families are highly recommended.

Journal ArticleDOI
TL;DR: In this article, a 20-day-old term infant presented with recurrent apnoea, lethargy and respiratory failure, without any signs of respiratory distress requiring initiation of noninvasive positive pressure ventilation (NPPV).
Abstract: A 20-day-old term infant presented with recurrent apnoea, lethargy and respiratory failure. Examination revealed episodes of apnoea and desaturation to 85% without any signs of respiratory distress requiring initiation of non-invasive positive pressure ventilation (NPPV). Capillary blood gas was indicative of respiratory acidosis and serum bicarbonate was elevated at 35 mmol/L. Chest radiograph, echocardiogram and evaluations for infectious aetiologies resulted normal. Due to inability to wean off NPPV with ensuing apnoea and desaturation, polysomnogram was performed and showed central and obstructive sleep apnoea, hypoxaemia and hypoventilation. Central apnoeas and hypoventilation were worse in non-rapid eye movement sleep. Paired-like homeobox 2B genetic studies showed a novel non-polyalanine repeat mutation (c.429+1G>A) establishing the diagnosis of congenital central hypoventilation syndrome (CCHS). Our case highlights the utility of polysomnography in the evaluation of term infants with apnoea. Although rare, clinicians should consider a diagnosis of CCHS in the evaluation of infants with apnoea and hypoventilation.

Journal ArticleDOI
TL;DR: Average volume-assured pressure support (AVAPS) as mentioned in this paper is a modality of noninvasive ventilation that provides a targeted tidal volume by automatically adjusting the inspiratory pressure.
Abstract: Study Objectives:Average volume-assured pressure support (AVAPS) is a modality of noninvasive ventilation that provides a targeted tidal volume by automatically adjusting the inspiratory pressure s...

Journal ArticleDOI
TL;DR: In this paper, a prospective observational study was conducted in two centers and included older adults (≥75-year-old) or obese (body mass index) patients who were at high risk of hypoventilation.
Abstract: Respiratory compromise (RC) including hypoxia and hypoventilation is likely to be missed in the postoperative period. Integrated pulmonary index (IPI) is a comprehensive respiratory parameter evaluating ventilation and oxygenation. It is calculated from four parameters: end-tidal carbon dioxide, respiratory rate, oxygen saturation measured by pulse oximetry (SpO2), and pulse rate. We hypothesized that IPI monitoring can help predict the occurrence of RC in patients at high-risk of hypoventilation in post-anesthesia care units (PACUs). This prospective observational study was conducted in two centers and included older adults (≥ 75-year-old) or obese (body mass index ≥ 28) patients who were at high-risk of hypoventilation. Monitoring was started on admission to the PACU after elective surgery under general anesthesia. We investigated the onset of RC defined as respiratory events with prolonged stay in the PACU or transfer to the intensive care units; airway narrowing, hypoxemia, hypercapnia, wheezing, apnea, and any other events that were judged to require interventions. We evaluated the relationship between several initial parameters in the PACU and the occurrence of RC. Additionally, we analyzed the relationship between IPI fluctuation during PACU stay and the occurrences of RC using individual standard deviations of the IPI every five minutes (IPI-SDs). In total, 288 patients were included (199 elderly, 66 obese, and 23 elderly and obese). Among them, 18 patients (6.3 %) developed RC. The initial IPI and SpO2 values in the PACU in the RC group were significantly lower than those in the non-RC group (6.7 ± 2.5 vs. 9.0 ± 1.3, p < 0.001 and 95.9 ± 4.2 % vs. 98.3 ± 1.9 %, p = 0.040, respectively). We used the area under the receiver operating characteristic curves (AUC) to evaluate their ability to predict RC. The AUCs of the IPI and SpO2 were 0.80 (0.69–0.91) and 0.64 (0.48–0.80), respectively. The IPI-SD, evaluating fluctuation, was significantly greater in the RC group than in the non-RC group (1.47 ± 0.74 vs. 0.93 ± 0.74, p = 0.002). Our study showed that low value of the initial IPI and the fluctuating IPI after admission to the PACU predict the occurrence of RC. The IPI might be useful for respiratory monitoring in PACUs and ICUs after general anesthesia.

Journal ArticleDOI
TL;DR: A patient with profound congenital hypotonia, central hypoventilation, poor visual behavior with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress was reported in this article.
Abstract: We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTM variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTM encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.

Journal ArticleDOI
TL;DR: In this article, the authors investigated whether day-time tests of respiratory muscle function and diaphragm ultrasound predict hypercapnia during sleep in 27 patients with genetic myopathies (myotonic dystrophy type 1 and 2, late-onset Pompe disease, facioscapulohumeral dystroke; 48 ± 11 years).
Abstract: Introduction: In slowly progressive myopathies, diaphragm weakness early manifests through sleep-related hypoventilation as reflected by nocturnal hypercapnia. This study investigated whether daytime tests of respiratory muscle function and diaphragm ultrasound predict hypercapnia during sleep. Methods: Twenty-seven patients with genetic myopathies (myotonic dystrophy type 1 and 2, late-onset Pompe disease, facioscapulohumeral dystrophy; 48 ± 11 years) underwent overnight transcutaneous capnometry, spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Results: Sixteen out of 27 patients showed nocturnal hypercapnia (peak ptcCO2 ≥ 50 mmHg for ≥ 30 min or increase in ptcCO2 by 10 mmHg or more from the baseline value). In these patients, forced vital capacity (FVC; % predicted) and maximum inspiratory pressure (MIP; % of lower limit or normal or LLN) were significantly reduced compared to normocapnic individuals. Nocturnal hypercapnia was predicted by reduction in FVC of 8.0 cm/s on diaphragm ultrasound.

Journal ArticleDOI
TL;DR: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awakehypercapnia, regardless of the severity of baseline hypercapnia.
Abstract: Rationale Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity. Objective To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups. Methods Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI) ≥ 30 events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45–49.9 or ≥50 mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model. Results 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups. Conclusion In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the isolated effects of changes in ventilation on ∆PCO2, eight pigs were studied in a prospective observational cohort, and the changes from baseline were analysed using repeated measures ANOVA with post-hoc analysis using Bonferroni's correction.
Abstract: Background Early diagnosis of shock is a predetermining factor for a good prognosis in intensive care. An elevated central venous to arterial PCO2 difference (∆PCO2) over 0.8 kPa (6 mm Hg) is indicative of low blood flow states. Disturbances around the time of blood sampling could result in inaccurate calculations of ∆PCO2, thereby misrepresenting the patient status. This study aimed to determine the influences of acute changes in ventilation on ∆PCO2 and understand its clinical implications. Methods To investigate the isolated effects of changes in ventilation on ∆PCO2, eight pigs were studied in a prospective observational cohort. Arterial and central venous catheters were inserted following anaesthetisation. Baseline ventilator settings were titrated to achieve an EtCO2 of 5±0.5 kPa (VT = 8 mL/kg, Freq = 14 ± 2/min). Blood was sampled simultaneously from both catheters at baseline and 30, 60, 90, 120, 180 and 240 s after a change in ventilation. Pigs were subjected to both hyperventilation and hypoventilation, wherein the respiratory frequency was doubled or halved from baseline. ∆PCO2 changes from baseline were analysed using repeated measures ANOVA with post-hoc analysis using Bonferroni’s correction. Results ∆PCO2 at baseline for all pigs was 0.76±0.29 kPa (5.7±2.2 mm Hg). Following hyperventilation, there was a rapid increase in the ∆PCO2, increasing maximally to 1.35±0.29 kPa (10.1±2.2 mm Hg). A corresponding decrease in the ∆PCO2 was seen following hypoventilation, decreasing maximally to 0.23±0.31 kPa (1.7±2.3 mm Hg). These changes were statistically significant from baseline 30 s after the change in ventilation. Conclusion Disturbances around the time of blood sampling can rapidly affect the PCO2, leading to inaccurate calculations of the ∆PCO2, resulting in misinterpretation of patient status. Care should be taken when interpreting blood gases, if there is doubt as to the presence of acute and transient changes in ventilation.

Journal ArticleDOI
TL;DR: In this article, the authors show that acute hypercapnic respiratory failure has been associated with worse outcomes for various disease states, but less is known about patients with compensated hypercapric respirations.
Abstract: Rationale: Acute hypercapnic respiratory failure has been shown to be associated with worse outcomes for various disease states, but less is known about patients with compensated hypercapnic respir...

Journal ArticleDOI
TL;DR: Both shamSH and SH groups have extra CO 2 load during and between SH periods, indicating that the SH/shamSH patients may represent a separate group of true hypoventilators during sleep.
Abstract: An increase in PaCO2 is the element that defines sleep hypoventilation (SH). We queried if patients with SH, and those with PaCO2 increases during sleep for shorter time periods than SH (shamSH) differed from the patients without SH (noSH) in other ways. This was a retrospective re-analysis of data from 100 stable inpatients with COPD with and without chronic hypercapnic respiratory failure. COPD was defined by criteria of the Global initiative for Chronic Obstructive Lung Disease (GOLD). For this study, SH was defined by an increase in PaCO2 ≥ 1.33 kPa to a value exceeding 6.7 kPa for ≥ 10 min (≥ 20 epochs of 30 s). Patients fulfilling the increase in PaCO2 for less than 10 min (1–19 epochs) were designated shamSH. All patients had daytime arterial blood gases, lung function tests, and polysomnography (PSG) with transcutaneous CO2 (PtcCO2). Of 100 patients, 25 had PtcCO2 increase ≥ 1.33 kPa. One never exceeded 6.7 kPa, 15 had SH, and 9 shamSH. SH and shamSH patients had extra CO2 load (= PtcCO2*time) both during and between the SH periods compared to the noSH group, the SH group more than the shamSH group. Using CO2 load as a measure of severity of sleep hypoventilation, SH patients have worse hypoventilation than the shamSH. Both shamSH and SH groups have extra CO2 load during and between SH periods, indicating that the SH/shamSH patients may represent a separate group of true hypoventilators during sleep.

Journal ArticleDOI
TL;DR: Support is provided for respiratory dysregulation as a feature of PD and the utility of HVT respiratory recovery as treatment outcome measure for respiration-based PD therapy is demonstrated.

Posted ContentDOI
16 Feb 2021-bioRxiv
TL;DR: In this paper, a system combining pneumotachography and laser detection of abdominal movement immediately after birth was used to classify central, obstructive or mixed apneas in infants with Congenital Central Hypoventilation Syndrome.
Abstract: RationaleCongenital Central Hypoventilation Syndrome is characterized by life-threatening sleep hypoventilation, and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation. Patients require lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. ObjectivesTo determine whether Phox2b27Ala/+ mice, which presented main symptoms of Congenital Central Hypoventilation Syndrome and died within hours after birth, also presented obstructive apneas and investigate potential underlying mechanisms. MethodsApneas were classified as central, obstructive or mixed by using an original system combining pneumotachography and laser detection of abdominal movement immediately after birth. Some respiratory nuclei involved in airway patency were analyzed by immunohistochemistry and electrophysiology in brainstem-spinal cord preparation. Measurements and Main ResultsThe median (interquartile range) of obstructive apnea frequency was 2.3/min (1.5-3.3) in Phox2b27Ala/+ pups versus 0.6/min (0.4-1.0) in wildtypes (P < 0.0001). Obstructive apnea duration was 2.7s (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7s (1.1- 1.9) in wildtypes (P < 0.0001). Central and mixed apneas presented similar, significant differences. In Phox2b27Ala/+ preparations, hypoglossal nucleus had fewer neurons (P < 0.05) and smaller size (P < 0.01), compared to wildtypes. Importantly, coordination of phrenic and hypoglossal activities was disrupted, as shown by the longer and variable delay of hypoglossal with respect to phrenic onset, compared to wildtypes (P < 0.001). ConclusionsThe Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also obstructive and mixed apneas likely due to hypoglossal dysgenesis. These results call for attention toward obstructive events in infants with Congenital Central Hypoventilation Syndrome. Subject category15.1 Animal Models of Sleep Apnea

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TL;DR: In this paper, the authors performed in vivo recordings from medullary respiratory neurons on the RTT rat model and found that the abnormal respiratory neuronal firing, ectopic phrenic discharge as well as RTT-type hypoventilation all can be corrected by enhancing GABAergic inhibition.
Abstract: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by mutations in the MECP2 gene. RTT patients show periodical hypoventilation attacks. The breathing disorder contributing to the high incidence of sudden death is thought to be due to depressed central inspiratory (I) activity via unknown cellular processes. Demonstration of such processes may lead to targets for pharmacological control of the RTT-type hypoventilation. We performed in vivo recordings from medullary respiratory neurons on the RTT rat model. To our surprise, both I and expiratory (E) neurons in the ventral respiratory column (VRC) increased their firing activity in Mecp2-null rats with severe hypoventilation. These I neurons including E-I phase-spanning and other I neurons remained active during apneas. Consistent with enhanced central I drive, ectopic phrenic discharges during expiration as well as apnea were observed in the Mecp2-null rats. Considering the increased I neuronal firing and ectopic phrenic activity, the RTT-type hypoventilation does not seem to be caused by depression in central I activity, neither reduced medullary I premotor output. This as well as excessive E neuronal firing as shown in our previous studies suggests inadequate synaptic inhibition for phase transition. We found that the abnormal respiratory neuronal firing, ectopic phrenic discharge as well as RTT-type hypoventilation all can be corrected by enhancing GABAergic inhibition. More strikingly, Mecp2-null rats reaching humane endpoints with severe hypoventilation can be rescued by GABAergic augmentation. Thus, defective GABAergic inhibition among respiratory neurons is likely to play a role in the RTT-type hypoventilation, which can be effectively controlled with pharmacological agents.

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TL;DR: In patients with myotonic dystrophy with Type II respiratory failure maintaining adherence is challenging, and the impact of NIV adherence on hypercapnia and symptoms of hypoventilation in patients with DM1 is investigated.
Abstract: Type 1 myotonic dystrophy (DM1) causes sleep disordered breathing and respiratory failure due to a combination of obstructive sleep apnoea, reduced central drive and respiratory muscle weakness. Noninvasive ventilation (NIV) is commonly used for treating respiratory failure in neuromuscular disease; however, there have been few studies assessing the role of NIV in DM1. The aim of this retrospective service evaluation was to investigate the impact of NIV adherence on hypercapnia and symptoms of hypoventilation in patients with DM1. Data on capillary carbon dioxide tension (P CO2 ), lung function, adherence to NIV and symptoms of hypoventilation were obtained from the records of 40 patients with DM1. Mean capillary P CO2 significantly reduced from 6.81±1.17 kPa during supervised inpatient set-up to 5.93±0.82 kPa after NIV set-up (p<0.001). NIV adherence reduced from 7.8 (range: 1.0-11.0) h per 24 h during supervised inpatient set-up to 2.9 (0-10.4) h per 24 h in the community. Overall 72% of patients used NIV <5 h per 24 h during follow-up, including 11% who discontinued NIV completely. There was no correlation between adherence to NIV and changes in capillary P CO2 . Patients who reported symptomatic benefit (50%) had higher adherence than those who did not feel benefit (p<0.05). In conclusion, in patients with myotonic dystrophy with Type II respiratory failure maintaining adherence is challenging.

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TL;DR: In this paper, a literature search of PubMed, CINAHL, and SCOPUS identified studies from 2009 through 2019 addressing the effects of ventilation during the initial post-trauma resuscitation on patient outcomes.
Abstract: Objectives: In the absence of evidence of acute cerebral herniation, normal ventilation is recommended for patients with traumatic brain injury (TBI). Despite this recommendation, ventilation strategies vary during the initial management of patients with TBI and may impact outcome. The goal of this systematic review was to define the best evidence-based practice of ventilation management during the initial resuscitation period. Methods: A literature search of PubMed, CINAHL, and SCOPUS identified studies from 2009 through 2019 addressing the effects of ventilation during the initial post-trauma resuscitation on patient outcomes. Results: The initial search yielded 899 articles, from which 13 were relevant and selected for full-text review. Six of the 13 articles met the inclusion criteria, all of which reported on patients with TBI. Either end-tidal carbon dioxide (ETCO2) or partial pressure carbon dioxide (PCO2) were the independent variables associated with mortality. Decreased rates of mortality were reported in patients with normal PCO2 or ETCO2. Conclusions: Normoventilation, as measured by ETCO2 or PCO2, is associated with decreased mortality in patients with TBI. Preventing hyperventilation or hypoventilation in patients with TBI during the early resuscitation phase could improve outcome after TBI.

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TL;DR: In this paper, the occurrence of post-operative hypoventilation in dogs undergoing decompressive ventral slot or hemilaminectomy for the treatment of intervertebral disc herniation (IVDH) was documented.
Abstract: The objective of this prospective cohort study was to document the occurrence of post-operative hypoventilation in dogs undergoing decompressive ventral slot or hemilaminectomy for the treatment of intervertebral disc herniation (IVDH). Twenty dogs undergoing ventral slot surgery and 20 dogs undergoing hemilaminectomy surgery for the treatment of IVDH that presented to XX between 2017 and 2020 were enrolled. Dogs were anesthetized using a standard protocol. Blood gas samples were taken at up to 11 time points beginning during anesthetic recovery and continuing for a maximum of 72 h post-operatively. Dogs with cervical lesions that were non-ambulatory before surgery had more evidence of subclinical hypoventilation in the immediate peri-extubation period than dogs with less severe injuries or those undergoing hemilaminectomy surgery. We found no difference in the ventilation status in dogs undergoing cervical or thoracolumbar decompressive surgery for IVDH from 8 to 72 h post-operatively. Other markers of acid-base status indicated that subclinical hypoventilation within the peri-extubation period was transient and self-limiting. There was a moderate positive correlation between sedation scores and estimated PaCO2. These data suggest that dogs with severe cervical spinal cord injuries may be at risk for subclinical hypoventilation in the immediate peri-extubation period. Increased sedation may be correlated with decreased ventilatory status in dogs recovering from decompressive vertebral column surgery.

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TL;DR: In this paper, clinical, EEG, brain MRI data, and antibodies against human neuronal antigens (NMDAR, GABAR, AMPAR, LGI1, CASPR2, and GAD) from 158 patients with criteria for possible autoimmune encephalitis were analyzed to create a predictive model for this disease.
Abstract: Objective To identify clinical variables that could predict the presence of autoantibodies in patients with acute encephalitis. Methods An observational, retrospective study from May 2011 to May 2017. Clinical, EEG, brain MRI data, and antibodies against human neuronal antigens (NMDAR, GABAR, AMPAR, LGI1, CASPR2, and GAD) from 158 patients with criteria for possible autoimmune encephalitis were analyzed to create a predictive model for this disease. Results We analyzed 158 samples, of which 18 cases were positive for anti-NMDAR, 2 for anti-LGI1, and 2 for anti-GAD. Seven of the 18 positive NMDAR patients were children, and 12 were female. Behavioral disorder, epileptic seizures, movement disorder, and altered level of consciousness were the frequent symptoms with >75 % sensitivity in positive anti-NMDAR patients. Other symptoms, such as language disorder, psychosis, hypoventilation, altered wake and sleep cycle, and cognitive impairment, had a sensitivity >55 %. Abnormal EEG findings had a high sensitivity (99.4 %). Brain MRI suggestive of encephalitis was observed in 7 of the positive cases for NMDAR. Abnormal CSF findings were reported in 12 patients positive for this receptor (sensitivity 70.6 %). With 7 of these symptoms, we obtained a sensitivity of 70 % and specificity of 81 % for the presence of anti-NMDAR antibodies (ROC Area 82 %). However, to predict that a patient with subacute encephalitis may have an autoimmune cause, the patient should include clinical manifestations such as movement disorder, behavioral disorder, hypoventilation, dysautonomia, and alteration of the wake and sleep cycle. Children were significantly more likely than adults with autoimmune encephalitis to experience chorea and status epilepticus (p Conclusions Anti-NMDAR encephalitis was more frequent in females and children. The repertoire of autoimmune encephalitis in children is different from adults. The presence of subacute behavioral changes, epileptic seizures, movement disorders, altered consciousness, hypoventilation, dysautonomia, and altered wake and sleep cycle predicted autoimmune encephalitis in our series.

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TL;DR: Clinical-exome-sequencing revealed SLC25A4-related mitochondrial deoxyribonucleic acid (DNA) depletion syndrome-12A (cardiomyopathic type), apparent at birth and carries a poor prognosis.
Abstract: Congenital hypotonia and hypoventilation is a rare association. We report a rare case of a female newborn with poor respiratory drive, ventilator dependency, severe hypotonia, cardiomyopathy, and premature death. Clinical-exome-sequencing revealed SLC25A4-related mitochondrial deoxyribonucleic acid (DNA) depletion syndrome-12A (cardiomyopathic type). This syndrome is apparent at birth and carries a poor prognosis.