Showing papers on "Hypoventilation published in 2018"

Severe peri-ictal respiratory dysfunction is common in Dravet syndrome

Abstract: Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of sudden unexplained death in epilepsy (SUDEP), widely believed to be due to cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal respiratory dysfunction. One patient had severe and prolonged postictal hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia. Death could be prevented with mechanical ventilation after seizures were induced by hyperthermia or maximal electroshock. Muscarinic receptor antagonists did not prevent bradycardia or death when given at doses selective for peripheral parasympathetic blockade, whereas apnea, bradycardia, and death were prevented by the same drugs given at doses high enough to cross the blood-brain barrier. When given via intracerebroventricular infusion at a very low dose, a muscarinic receptor antagonist prevented apnea, bradycardia, and death. We conclude that SUDEP in patients with DS can result from primary central apnea, which can cause bradycardia, presumably via a direct effect of hypoxemia on cardiac muscle.

Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review

Abstract: Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.

Relationships between MRI fat distributions and sleep apnea and obesity hypoventilation syndrome in very obese patients

Abstract: Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p < 0.001). Gender was a significant confounder in these associations. No significant associations were found between MRI measures of adiposity and hypoventilation. In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.

Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity.

Abstract: Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). Arterial blood gas was measured in nine obese and nine lean mice during wakefulness. Nine male mice with DIO and six lean male C57BL/6J mice were head mounted with electroencephalogram (EEG) and electromyogram (EMG) electrodes. Sleep recordings were performed in the whole body plethysmography chamber; upper airway obstruction was characterized by the presence of inspiratory flow limitation in which airflow plateaus with increases in inspiratory effort. Obese mice showed significantly lower pH and higher partial pressure of arterial CO2 (PaCO2) in arterial blood gas compared to lean mice, 7.35 ± 0.04 versus 7.46 ± 0.06 (p < 0.001) and 38 ± 8 mm Hg versus 30 ± 5 mm Hg (p < 0.001). Obese mice had similar levels of minute ventilation to lean mice during sleep and wakefulness, despite higher body weight and temperature, indicating an increase in the metabolic rate and hypoventilation. Obese mice also showed baseline hypoxemia with decreased mean oxyhemoglobin saturation across sleep/wake states. Obese mice had a higher prevalence of flow-limited breathing compared to lean mice during sleep. However, the oxygen desaturation index in lean and obese mice did not differ. We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.

Sleep-disordered breathing in patients with neuromuscular disease.

Abstract: Sleep-disordered breathing (SDB) is relatively common in general population as well as in patients with neuromuscular disease. SDB comprises a wide spectrum of disorders varying from simple snoring to complete closure of the upper airway as seen in obstructive sleep apnoea (OSA). It includes also other disorders like prolonged hypoxemia, hypoventilation, and central sleep apnoea (CSA). Neuromuscular diseases (NMD) form a group of disorders that can cause significant reduction in the quality and span of life. The involvement of respiratory system in the context of these disorders is the most serious complication, and it is considered as the leading cause of death in those patients. NMD can affect ventilation, cough, swallowing, and phonation. The involvement of respiratory muscles makes NMD patients vulnerable to sleep-disordered breathing with a significant prevalence of SDB among such patients.

Obesity hypoventilation syndrome: a current review.

Abstract: Obesity hypoventilation syndrome (OHS) is defined as the presence of obesity (body mass index ≥ 30 kg/m²) and daytime arterial hypercapnia (PaCO2 ≥ 45 mmHg) in the absence of other causes of hypoventilation. OHS is often overlooked and confused with other conditions associated with hypoventilation, particularly COPD. The recognition of OHS is important because of its high prevalence and the fact that, if left untreated, it is associated with high morbidity and mortality. In the present review, we address recent advances in the pathophysiology and management of OHS, the usefulness of determination of venous bicarbonate in screening for OHS, and diagnostic criteria for OHS that eliminate the need for polysomnography. In addition, we review advances in the treatment of OHS, including behavioral measures, and recent studies comparing the efficacy of continuous positive airway pressure with that of noninvasive ventilation.

ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison.

Abstract: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a very rare and potentially fatal pediatric disorder, the cause of which is presently unknown. ROHHAD is often compared to Prader-Willi syndrome (PWS) because both share childhood obesity as one of their most prominent and recognizable signs, and because other symptoms such as hypoventilation and autonomic dysfunction are seen in both. These phenotypic similarities suggest they might be etiologically related conditions. We performed an in-depth clinical comparison of the phenotypes of ROHHAD and PWS and used NGS and Sanger sequencing to analyze the coding regions of genes in the PWS region among seven ROHHAD probands. Detailed clinical comparison of ROHHAD and PWS patients revealed many important differences between the phenotypes. In particular, we highlight the fact that the areas of apparent overlap (childhood-onset obesity, hypoventilation, autonomic dysfunction) actually differ in fundamental ways, including different forms and severity of hypoventilation, different rates of obesity onset, and different manifestations of autonomic dysfunction. We did not detect any disease-causing mutations within PWS candidate genes in ROHHAD probands. ROHHAD and PWS are clinically distinct conditions, and do not share a genetic etiology. Our detailed clinical comparison and genetic analyses should assist physicians in timely distinction between the two disorders in obese children. Of particular importance, ROHHAD patients will have had a normal and healthy first year of life; something that is never seen in infants with PWS.

Obesity Hypoventilation Syndrome: Early Detection of Nocturnal-Only Hypercapnia in an Obese Population.

Abstract: STUDY OBJECTIVES Hypoventilation in obesity is now divided into five stages; stage 0 (pure obstructive sleep apnea; OSA), stages I/II (obesity-related sleep hypoventilation; ORSH) and stages III/IV (awake hypercapnia, obesity hypoventilation syndrome; OHS). Hypercapnia during the day may be preceded by hypoventilation during sleep. The goal of this study was to determine the prevalence and to identify simple clinical measures that predict stages I/II ORSH. The effect of supine positioning on selected clinical measures was also evaluated. METHODS Ninety-four patients with a body mass index > 40 kg/m2 and a spirometric ratio > 0.7 were randomized to begin testing either in the supine or upright seated position on the day of their diagnostic sleep study. Arterialized capillary blood gases were measured in both positions. Oxygen saturation measured by pulse oximetry was also obtained while awake. Transcutaneous CO2 monitoring was performed during overnight polysomnography. RESULTS Stages I/II ORSH had a prevalence of 19% in an outpatient tertiary hospital setting compared with 61%, 17%, and 3% for stages 0, III/IV, and no sleep-disordered breathing respectively. Predictors for sleep hypoventilation in this group were an awake oxygen saturation of ≤ 93% (sensitivity 39%, specificity 98%, positive likelihood ratio of 22) and a partial pressure of carbon dioxide ≥ 45 mmHg (sensitivity 44%, specificity 98%, positive likelihood ratio of 24) measured in the supine position. CONCLUSIONS ORSH has a similar prevalence to OHS. Awake oxygen saturation and partial pressure of carbon dioxide performed in the supine position may help predict obese patients with sleep hypoventilation without awake hypercapnia. COMMENTARY A commentary on this article appears in this issue on page 1455. CLINICAL TRIAL REGISTRATION Registry: Australian New Zealand Clinical Trials Registry, Identifier: ACTRN 12615000135516, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367493&isReview=true, Title: A cross-sectional study to identify obese patients who are at risk for developing obesity hypoventilation syndrome (OHS) by investigating the relationship between daytime measures (including supine hypercapnia, distribution of body fat and lung volumes) with the presence of hypoventilation during sleep.

Detection of early nocturnal hypoventilation in neuromuscular disorders

Abstract: ObjectiveNocturnal hypoventilation (NH) is a complication of respiratory involvement in neuromuscular disorders (NMD) that can evolve into symptomatic daytime hypercapnia if not treated proactively...

Portable multi-parameter electrical impedance tomography for sleep apnea and hypoventilation monitoring: feasibility study.

Abstract: Objective Quantitative ventilation monitoring and respiratory event detection are needed for the diagnosis of sleep apnea and hypoventilation. We developed a portable device with a chest belt, nasal cannula and finger sensor to continuously acquire multi-channel signals including tidal volume, nasal pressure, respiratory effort, body position, snoring sound, ECG and SpO2. The unique feature of the device is the continuous tidal volume signal obtained from real-time lung ventilation images produced by the electrical impedance tomography (EIT) technique. Approach The chest belt includes 16 electrodes for real-time time-difference EIT imaging and ECG data acquisitions. It also includes a microphone, accelerometer, gyroscope, magnetometer and pressure sensor to acquire, respectively, snoring sound, respiratory effort, body position and nasal pressure signals. A separate finger sensor is used to measure SpO2. The minute ventilation signal is derived from the tidal volume signal and respiration rate. Main results The experimental results from a conductivity phantom, four swine subjects and one human volunteer show that the developed multi-parameter EIT device could supplement existing polysomnography (PSG) and home sleep test (HST) devices to improve the accuracy of sleep apnea diagnosis. The portable device could be also used as a new tool for continuous hypoventilation monitoring of non-intubated patients with respiratory depression. Significance Following the feasibility study in this paper, future validation studies in comparison with in-lab PSG, HST and end-tidal CO2 devices are suggested to find its clinical efficacy as a sleep apnea diagnosis and hypoventilation monitoring tool.

Respiratory Instability and Hypoxemia Episodes in Preterm Infants.

Abstract: Oxygenation instability is a very common problem in the premature infant that manifests as intermittent hypoxemia episodes (HEs). These are particularly frequent in premature infants who are on mechanical ventilation beyond the first weeks after birth. However, they can also occur in spontaneously breathing infants. Some of these episodes are due to central apnea, but in ventilated infants, they are frequently due to contractions of the abdominal musculature that can splint the respiratory pump, resulting in periods of decreased lung volume and hypoventilation. HEs are often followed by periods of hyperoxemia that results from excessive oxygen supplementation given to correct the hypoxemia. These episodes increase in frequency with postnatal age and are more common in infants with chronic lung disease. Although the evidence is not conclusive, their detrimental effects on the infant's neurologic, ocular, and respiratory system may be significant. There is no specific treatment for HEs, but several interventions are available to ameliorate the severity and duration of the episodes. Further research is needed to define the impact of HEs on the preterm infant's developing central nervous system and other organ systems and to develop effective strategies to prevent these episodes.

Repeated-sprint training in hypoxia induced by voluntary hypoventilation improves running repeated-sprint ability in rugby players.

Abstract: Purpose: The goal of this study was to determine the effects of repeated-sprint training in hypoxia induced by voluntary hypoventilation at low lung volume (VHL) on running repeated-sprint ability ...

Cardiorespiratory evaluation of brachycephalic syndrome in dogs

Abstract: Brachycephalic syndrome (BS) in dogs is characterized by the combination of primary and secondary upper respiratory tract abnormalities and may result in significant upper airway obstruction. It can trigger inspiratory dyspnea, culminating in secondary respiratory distress, soft tissue edema, upper airway obstruction, turbulent airflow, inspiratory noise, and even death. These changes lead to increased resistance of the air passages, which can cause elevation of pulmonary pressure and clinical manifestations attributable to pulmonary hypertension. The consequence is right-sided cardiac remodeling (Cor pulmonale) with possible progression to right congestive heart failure. To investigate the effects of BS on the cardiovascular system, 28 animals were recruited for a prospective study and assigned to either the Brachycephalic Group (BG), composed of 22 French bulldogs with BS or the Control Group (CG), which was composed of 6 healthy Beagle dogs. All animals underwent a detailed physical examination, as well as laboratory analyses, electrocardiography, echocardiography, chest radiography and indirect measurement of systemic arterial blood pressure. The most relevant finding was a lower PaO2 (90.6±12.9mmHg) in BG as compared to CG (104.9±5.2), (p≤0.05), possibly attributable to hypoventilation due to anatomical alterations.

Risk of Left Atrial Enlargement in Obese Patients With Obesity-Induced Hypoventilation Syndrome vs Obstructive Sleep Apnea

Abstract: Background: Obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF) that is principally driven by left atrial enlargement. The impact of hypoventilation caused by obesity-induced hypoventilation syndrome (OHS) on left atrial diameter has not been examined. We investigated the association between OHS and left atrial diameter in obese patients. Methods: We performed a retrospective review of 210 consecutive medical records of patients diagnosed as obese (body mass index [BMI] >30 kg/m2) and as having OHS and OSA for the period January 2010 through December 2016 at St. Vincent Charity Medical Center in Cleveland, OH. Logistic regression analysis was performed for left atrial diameter ≥4 cm in 2 groups of patients: those with OHS+OSA and those with OSA alone. Results: A total of 104 obese patients with OHS+OSA and 106 obese patients with OSA alone were identified. Statistically significant differences were found in 6 demographic and baseline characteristics: median BMI, median left atrial diameter, history of type 2 diabetes mellitus, history of stroke, history of coronary artery disease, and history of congestive heart failure. The median left atrial diameter for the OHS+OSA and OSA alone groups was 4.45 cm and 4.20 cm, respectively (P = 0.014). Left ventricular ejection fraction Conclusion: The results of this study indicate that OHS may be an independent risk factor for left atrial enlargement and may possibly contribute to AF development irrespective of left ventricular function.

Patterns of use, survival and prognostic factors in patients receiving home mechanical ventilation in Western Australia: A single centre historical cohort study.

Abstract: Home mechanical ventilation (HMV) is used in a wide range of disorders associated with chronic hypoventilation. We describe the patterns of use, survival and predictors of death in Western Australia. We identified 240 consecutive patients (60% male; mean age 58 years and body mass index 31 kg m−2) referred for HMV between 2005 and 2010. The patients were grouped into four categories: motor neurone disorders (MND; 39%), pulmonary disease (PULM; 25%, mainly chronic obstructive pulmonary disease), non-MND neuromuscular and chest wall disorders (NMCW; 21%) and the obesity hypoventilation syndrome (OHS; 15%). On average, the patients had moderate ventilatory impairment (forced vital capacity: 51%predicted), sleep apnoea (apnoea-hypopnea index: 25 events h−1), sleep-related hypoventilation (transcutaneous carbon dioxide rise of 20 mmHg) and daytime hypercarbia (PCO2: 54 mmHg). Median durations of survival from HMV initiation were 1.0, 4.2, 9.9 and >11.5 years for MND, PULM, NMCW and OHS, respectively. Independe...

Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation.

Abstract: BACKGROUND Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation are rare neurocristopathies characterized by autonomic dysregulation including bradyarrhythmias, abnormal temperature control, and most significantly, abnormal control of breathing leading to tracheostomy and ventilator dependence as life support. Surgical advancements have made phrenic nerve-diaphragm pacemakers available, to eliminate the tether to a mechanical ventilator for 12-15 hours each day. The thoracoscopic approach to implantation has allowed for a less invasive approach which may have implications for pain control and recovery time. However, thoracoscopic implantation of these devices presents several challenges to the anesthesiologist in these complex ventilator-dependent patients, including, but not limited to, sequential lung isolation, prevention of hypothermia, and management of arrhythmias. Postoperative challenges may also include strategies to treat hemodynamic instability, managing the ventilator following lung derecruitment, and providing adequate pain control. AIMS We aimed to describe the anesthetic management of Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation patients undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation and the nature and incidence of perioperative complications. METHODS A retrospective chart review was performed of 14 children with Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation undergoing phrenic nerve-diaphragm pacemaker implantation at a single academic pediatric hospital between 2009 and 2017. Demographic information, intraoperative management, and perioperative complications were analyzed from patient records. RESULTS Twelve of 14 patients (86%) underwent an inhalational induction via tracheostomy. Lung isolation was achieved via fiberoptic guidance of a single lumen endotracheal tube sequentially into the right or left mainstem bronchi for 12 patients (86%). Double lumen endotracheal tubes were utilized in two patients (7%) and bronchial blockers in two patients (7%) for lung isolation. Anesthesia was maintained using a balanced technique of volatile agents (sevoflurane/isoflurane) and opioids (fentanyl). Bradyarrhythmias developed in six patients (43%) during surgery, 5 (36%) responded to anticholinergics and one patient (7%) required backup cardiac pacing using a previously implanted bipolar cardiac pacemaker. Intraoperative hypothermia ( 50 mm Hg) during lung isolation was present in eight patients (57%) and hemoglobin desaturation (<90%) in four patients (29%). Postoperatively, oxygen desaturation was a common complication with nine patients (64%) requiring supplemental oxygen administration via mechanical ventilator or manual bag ventilation. Opioids via patient-controlled analgesia devices (12 patients, 86%) or intermittent injection (two patients, 14%) were administered to all patients for postoperative pain control. Phrenic nerve-diaphragm pacemaker placement was successful thoracoscopically in all patients with no perioperative mortality. CONCLUSION The main anesthetic challenges in patients with Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation include hemodynamic instability, the propensity to develop hypothermia, hypercarbia/hypoxemia, and the need to perform bilateral sequential lung isolation requisite to the thoracoscopic implantation technique. Most anesthetic agents can be used safely in these patients; however, adequate knowledge of the susceptibility to complications, coupled with adequate preparation and understanding of the innate disease characteristics, are necessary to treat anticipated complications.

Perioperative Implementation of Noninvasive Positive Airway Pressure Therapies.

Abstract: Noninvasively applied positive airway pressure therapy (PAP) is available in 3 basic modes: continuous positive airway pressure (CPAP), bi-level positive airway pressure (BPAP), and adaptive servo-ventilation. These are in widespread use in home and hospital settings to treat a variety of disorders of ventilation or gas exchange, including obstructive sleep apnea, sleep-related hypoventilation, periodic breathing, acute and chronic hypercapnic respiratory failure, and acute respiratory failure. They are increasingly being used perioperatively to prevent or treat upper airway obstruction, hypoventilation, and periodic breathing, and they have been found to improve postoperative outcomes in the case of obstructive sleep apnea. An impediment to their use in this setting is a lack of familiarity with their application by hospital clinical staff. This review describes the modes of PAP therapy available, their indications, how therapy is initiated, how efficacy is assessed, common problems encountered with its use, and how these problems can be addressed.

ROHHAD Syndrome, a Rare Cause of Hypothalamic Obesity: Report of Two Cases

Abstract: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease have not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. Currently there are around 80 reported patients although this is likely due to underdiagnosis due to lack of recognition. We present two female patients suspected of ROHHAD due to weight gain starting in early childhood. Clinical and biochemical findings such as respiratory and circulatory dysfunction, hypothalamic hypernatremia, central hypothyrodism, hyperprolactinemia and central early puberty in these patients matched the criteria for ROHHAD syndrome. ROHHAD syndrome should be considered in the differential diagnosis of monogenic obesity.

Capnography Monitoring During Procedural Sedation and Analgesia

Abstract: Procedural sedation is used to alleviate pain and anxiety associated with diagnostic procedures in the acute care setting. Although commonly used, procedural sedation is not without risk. Key to reducing this risk is early identification of risk factors through presedation screening and monitoring during the procedure. Electrocardiogram, respiratory rate, blood pressure, and pulse oximetry commonly are monitored. These parameters do not reliably identify airway and ventilation compromise. Capnography measures exhaled carbon dioxide and provides early identification of airway obstruction and hypoventilation. Capnography is useful in patients receiving supplemental oxygen. In these patients, oxygen desaturation reported by pulse oximetry may lag during episodes of respiratory depression and apnea. Capnography indicates partial pressure of end-tidal carbon dioxide and provides information regarding airway integrity and patterns of ventilation compromise. Implementation of this technology may provide an additional layer of safety, reducing risk of respiratory compromise in patients receiving procedural sedation.

A devastating case of diarrhea-associated hemolytic uremic syndrome associated with extensive cerebral infarction; why we need to do better.

Abstract: A 4-year-old girl with diarrhea-associated hemolytic uremic syndrome (D+HUS) was transferred to the PICU of our center due to deteriorating renal function and neurological involvement. On admission, a comatous child was seen with hypoventilation and she was placed on mechanical ventilation. Hemodialysis was commenced but plasma exchange was discontinued due to repeated hypersensitivity reactions. A trial of eculizumab was given in light of the worsening of her neurologic condition with development of a pyramidal syndrome and deepening of the coma. Hematological and renal improvement were noted but severe neurologic involvement persisted. MRI revealed extensive bilateral zones of corticocerebral infarction and neurological damage proved to be irreversible. Diarrhea-associated hemolytic uremic syndrome is a common cause of Acute Kidney Injury associated with severe short- and long-term complications. Neurologic involvement is frequent but often reversible. Currently, no effective treatment strategies are available and a paucity of data exists concerning the efficacy of potential treatment options such as early plasma exchange, eculizumab, and high dose corticosteroids. A concerted effort is needed to early identify patients at risk for poor outcome with trials aimed at evaluating the efficacy of potential treatment options for this subgroup.

Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

Abstract: Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO2). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a "hypoventilation" might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Systemic oxidative stress in congenital central hypoventilation syndrome.

Abstract: The Congenital Central Hypoventilation Syndrome (CCHS), also known as Ondine's curse, is a rare disorder characterised by severe hypoventilation during sleep and autonomic dysregulation [1, 2] The incidence of CCHS is about 1/200 000 live births In more than 90% of cases, polyalanine repeat expansion (PolyALA) mutations are present in the paired-like homeobox PHOX-2B gene, although a frameshift variant (FS) may also be found [3] The PHOX-2B gene encodes a highly conserved homeobox domain transcription factor which plays a regulatory role in the differentiation of the motor neuron and the serotonergic neuronal fate in the development of the central nervous system [4] The hallmark of CCHS is the “forgotten breathing”, which implies the need for life-long mechanical ventilation during sleep However, in more severe cases characterised by global hypoventilation, mechanical ventilation must also be extended during wakefulness Ventilatory support may be provided by tracheostomy and assisted ventilation, non-invasive ventilation, or diaphragm pacemakers Severe respiratory depression typically arises at birth, but in milder cases, CCHS may be diagnosed later on in childhood or adulthood (later-onset CCHS) [1, 2] The clue to the respiratory defect is a reduced response to hypercapnia and hypoxemia depending on the malfunctioning of brainstem areas such as the retrotrapezoid nucleus, the parafacial respiratory group and the pre-Botzinger complex which are involved in the chemosensory drive to breathe [5–7] Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal It is published here in its accepted form prior to copyediting and typesetting by our production team After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online Please open or download the PDF to view this article Conflict of interest: Dr Becatti has nothing to disclose Conflict of interest: Dr Peruzzi has nothing to disclose Conflict of interest: Dr Fiorillo has nothing to disclose Conflict of interest: Dr Ramazzotti has nothing to disclose Conflict of interest: Dr Nassi has nothing to disclose Conflict of interest: Dr Arzilli has nothing to disclose Conflict of interest: Dr Piumelli has nothing to disclose Conflict of interest: Dr Degl'Innocenti has nothing to disclose

NERO: a pilot study but important step towards comprehensive management of obesity hypoventilation syndrome.

Abstract: The primary goal of treatment for obesity hypoventilation syndrome (OHS) has been to correct sleep-related breathing abnormalities, thereby reversing chronic respiratory failure. Nocturnal non-invasive ventilation (NIV) can achieve this and thus represents the cornerstone of respiratory management for this condition.1–4 While the effectiveness of NIV in improving clinical symptoms and quality of life has been convincingly demonstrated,2 3 5 the mortality rate of patients with OHS treated with NIV remains substantially higher than that of patients with obstructive sleep apnoea.6 Cardiovascular and metabolic comorbidities are the key determinants of a poorer prognosis.6 7 For several years, clinicians have suggested NIV treatment should be integrated into a comprehensive treatment plan that includes lifestyle modification and rehabilitation to further improve outcomes.8–10 In Thorax , Mandal and colleagues11 report the first randomised controlled trial evaluating the impact of a 3-month inpatient–outpatient multidisciplinary rehabilitation programme in addition to NIV compared with NIV alone in patients with OHS. Since weight loss is obviously the main treatment for OHS, the primary outcome chosen by the authors was change in weight at 12 months. Although no statistical difference between treatment …