Assessment of Chronic Hypercapnic Respiratory Failure.

Undiagnosed chronic hypercapnic respiratory failure may be encountered during the evaluation of sleep-related breathing disorders at the sleep clinic. This article reviews the mechanism of chronic hypercapnic respiratory failure and the systematic approach to the assessment of specific sleep disorders associated with nocturnal hypoventilation encountered in clinical practice.

Defective exercise-related expiratory muscle recruitment in patients with PHOX2B mutations: A clue to neural determinants of the congenital central hypoventilation syndrome.

INTRODUCTION AND OBJECTIVES: The human congenital central hypoventilation syndrome (CCHS) is caused by mutations in the PHOX2B (paired-like homeobox 2B) gene. Genetically engineered PHOX2B rodents exhibit defective development of the brainstem retrotrapezoid nucleus (RTN), a carbon dioxide sensitive structure that critically controls expiratory muscle recruitment. This has been linked to a blunted exercise ventilatory response. Whether this can be extrapolated to human CCHS is unknown and represents the objective of this study. MATERIALS AND METHODS: Thirteen adult CCHS patients and 13 healthy participants performed an incremental symptom-limited cycle cardiopulmonary exercise test. Responses were analyzed using guideline approaches (ventilation V'E, tidal volume VT, breathing frequency, oxygen consumption, carbon dioxide production) complemented by a breathing pattern analysis (i.e. expiratory and inspiratory reserve volume, ERV and IRV). RESULTS: A ventilatory response occurred in both study groups, as follows: V'E and VT increased in CCHS patients until 40 W and then decreased, which was not observed in the healthy participants (p<0.001). In the latter, exercise-related ERV and IRV decreases attested to concomitant expiratory and inspiratory recruitment. In the CCHS patients, inspiratory recruitment occurred but there was no evidence of expiratory recruitment (absence of any ERV decrease, p<0.001). CONCLUSIONS: Assuming a similar organization of respiratory rhythmogenesis in humans and rodents, the lack of exercise-related expiratory recruitment observed in our CCHS patients is compatible with a PHOX2B-related defect of a neural structure that would be analogous to the rodents' RTN. Provided corroboration, ERV recruitment could serve as a physiological outcome in studies aiming at correcting breathing control in CCHS.

Hypoventilation in patients with Prader-Willi syndrome across the pediatric age.

OBJECTIVES: Few data on alveolar hypoventilation in Prader-Willi syndrome (PWS) are available and the respiratory follow-up of these patients is not standardized. The objectives of this study were to evaluate the prevalence of alveolar hypoventilation in children with PWS and identify potential risk factors. STUDY DESIGN: This retrospective study included children with PWS recorded by polysomnography (PSG) with transcutaneous carbon dioxide pressure (PtcCO2) or end-tidal CO2 (ETCO2) measurements, between 2007 and 2021, in a tertiary hospital center. The primary outcome was the presence of alveolar hypoventilation defined as partial pressure of carbon dioxide (pCO2) ≥ 50 mmHg during ≥2% of total sleep time (TST) or more than five consecutive minutes. RESULTS: Among the 57 included children (38 boys, median age 4.8 years, range 0.1-15.6, 60% treated with growth hormone [GH], 37% obese), 19 (33%) had moderate-to-severe obstructive sleep apnea syndrome (defined as obstructive apnea-hypopnea index ≥5/h) and 20 (35%) had hypoventilation. The median (range) pCO2 max was 49 mmHg (38-69). Among the children with hypoventilation, 25% were asymptomatic. Median age and GH treatment were significantly higher in children with hypoventilation compared to those without. There was no significant difference in terms of sex, BMI, obstructive or central apnea-hypopnea index between both groups. CONCLUSION: The frequency of alveolar hypoventilation in children and adolescents with PWS is of concern and may increase with age and GH treatment. A regular screening by oximetry-capnography appears to be indicated whatever the sex, BMI, and rate of obstructive or central apneas.

Idiopathic Pulmonary Haemosiderosis: An Unusual Case Of Anaemia With Pulmonary Involvement.

Idiopathic pulmonary haemosiderosis is a rare disorder, with recurrent life-threatening alveolar haemorrhages and chronic lung parenchymal changes. It is associated with a triad of haemoptysis, iron deficiency anaemia, and diffuse pulmonary infiltrates. Although most cases are idiopathic, secondary haemosiderosis linked to known diseases has also been observed. Most of the cases remain undiagnosed because the disease is very low on the list of differentials. There is no specified age for the disease. The present study reports on an adolescent female patient who presented with microcytic anaemia and bilateral lung infiltrates to the National Institute of Child Health (NICH), Karachi, a tertiary care hospital. She was diagnosed with Idiopathic pulmonary haemosiderosis after ruling out other possibilities.

Case report: Central alveolar hypoventilation in a survivor of cardiopulmonary arrest.

Introduction: Ondine's curse is a rare respiratory disorder that is characterized by central alveolar hypoventilation (CAH) during sleep. It is most commonly congenital. However, it can also be acquired very rarely. Herein, we report a young survivor who developed CAH following cardiopulmonary arrest. Case presentation: A 35-year-old man was admitted to the Intensive Care Unit following unwitnessed cardiopulmonary arrest. Following resuscitative interventions, he remained comatose. Early diagnostic testing showed elevated neuronal specific enolase (28.7 ng/ml), absent cortical responses on evoked potential testing and MRI evidence of restricted diffusion in the cerebellum, hippocampi, juxtacortical white matter, superior cerebellar peduncles, dorsal pons, dorsolateral medulla, and upper cervical spinal cord. Ten days following admission, the patient remained comatose and underwent tracheostomy. He subsequently began to emerge from coma but had persistent unexplained hypotension and bradypnea necessitating ongoing vasopressor and respiratory support. Repeat MRI on hospital day 40 revealed residual FLAIR hyperintensities in the medulla within the nucleus tractus solitarius (NTS). After being discharged to long-term acute care facility, he was successfully liberated from mechanical ventilation 70 days post arrest. Conclusion: We report the first survivor of cardiopulmonary arrest who was complicated by CAH and hypotension with MRI verified ischemic injury to the bilateral NTS regions. Despite this injury, ventilator and vasopressor dependency resolved over a period of 10 weeks. Our case highlighted the essential functions of NTS in regulating the respiratory and cardiovascular systems.

A rare association: Obesity hypoventilation syndrome with myasthenia gravis and systemic lupus erythematosus, case report.

Background: Shrinking lung syndrome (SLS) is an uncommon complication of systemic lupus erythematosus (SLE) that has also been seen in other autoimmune diseases and is linked with a high risk of acute or chronic respiratory failure. Alveolar hypoventilation in the presence of obesity-hypoventilation syndrome, systemic lupus erythematosus (SLE), and myasthenia gravis (MG) is uncommon and poses a diagnostic and therapeutic challenge. Case report: We reported a 33-year-old female patient from Saudi Arabia who suffered from obesity, bronchial asthma, newly diagnosed essential hypertension, type 2 diabetes mellitus, with recurrent acute alveolar hypoventilation, secondary to obesity hypoventilation syndrome and mixed autoimmune disease (systemic lupus erythematosus and myasthenia gravis), based on the correct constellation of clinical findings and laboratory evidence. Conclusion: The interesting aspect of this case report: is the presentation of the overlap of obesity hypoventilation syndrome and shrinking lung syndrome due to systemic lupus erythematosus with generalized and respiratory muscle dysfunction due to myasthenia gravis with good outcomes after therapy.

Limitations of the apnea-hypopnea index in children and young adults with neuromuscular disorders.

There are no validated criteria to initiate noninvasive ventilation (NIV) in children and young adults with neuromuscular disease (NMD). In order to analyze NIV initiation criteria, we reviewed the polysomnography (PSG) criteria that led to the initiation of NIV in 61 consecutive patients with NMD, median age 4.1 (0.8-21) years, who had a PSG during their routine care. NIV was initiated on abnormal PSG data (apnea-hypopnea index (AHI) > 10 events/h and/or a transcutaneous carbon dioxide pressure > 50 mmHg and/or a pulse oximetry 〈 90%, both during at least 2% sleep time or 〉 5 consecutive minutes) in 11 (18%) patients. Six of these 11 patients had an AHI ≤ 10 events/h and would not have been ventilated if only AHI was retained. However, one of these 6 patients had isolated nocturnal hypoxemia, 3 isolated nocturnal hypercapnia and 2 abnormal respiratory events. Six (10%) patients with a normal PSG were started on NIV on clinical criteria. Our results show the limitation of the AHI when taken as the unique PSG criterion for NIV initiation in young patients with NMD and underline the need to include also abnormalities of overnight gas exchange into the NIV decision-making process.

Idiopathic Central Alveolar Hypoventilation wherein Sleep Disordered Breathing Was Considered Well-controlled by the Continuous Positive Airway Pressure Tracking System but Not Controlled by Polysomnography.

A 54-year-old man whose awake percutaneous arterial oxygen saturation (SpO2) was 94% was diagnosed with obstructive sleep apnea by polysomnography (PSG). His apnea-hypopnea index (AHI) was 138.8 (AI: 4.7 and HI: 134.1), so he was treated with continuous positive airway pressure (CPAP), and his condition was considered well-controlled by the CPAP tracking system (AHI=3.4), with improvement seen in his symptoms when he left our hospital. However, he returned to our hospital 4 years later with recurrent sleepiness and hypercapnia despite the well-controlled status (AHI=3.8) according to the tracking system. His hypercapnia improved following voluntary hyperventilation. Idiopathic central alveolar hypoventilation was diagnosed, with the AHI considered to be well-controlled by the CPAP tracking system but not at all according to PSG.

Novel Treatment of Ventilator Dyssynchrony From Central Alveolar Hypoventilation Syndrome Utilizing Scheduled 5-Hydroxytryptamine-3 Receptor Antagonist.

Traumatic brain injury (TBI) occurs in a large percentage of surgical trauma patients and is one of the leading causes of death amongst young teens and adults. Furthermore, individuals with TBIs often require mechanical ventilation and admission to the intensive care unit. As a result of their TBIs, these patients can develop central alveolar hypoventilation (CAH) secondary to disruptions in neuromodulatory respiratory brainstem control and neural signal initiation and integration. Prior studies have primarily focused their attention on treatment of congenital disorders of CAH, and limited research is available on intubated trauma patients who have signs of ventilator dyssynchrony. Current case reports and animal studies have suggested that noradrenergic and specific serotonergic medications are able to target specific neurologic pathways in the respiratory circuit and induce ventilator synchrony. This case series describes the clinical course of TBI patients treated for ventilator dyssynchrony secondary to CAH with a daily scheduled 5-hydroxytryptamine-3 (5-HT3) receptor antagonist. All patients were ultimately extubated and discharged from the hospital.

Pediatric Obstructive Sleep Apnea: What's in a Name?

Obstructive sleep apnea is a highly prevalent disease across the lifespan and imposes substantial morbidities, some of which may become irreversible if the condition is not diagnosed and treated in a timely fashion. Here, we focus on the clinical and epidemiological characteristics of pediatric obstructive sleep apnea, describe some of the elements that by virtue of their presence facilitate the emergence of disrupted sleep and breathing and its downstream consequences, and also discuss the potential approaches to diagnosis in at-risk children.

Anesthetic Implications for Patients With Implanted Hypoglossal Nerve Stimulators: A Case Report.

Obstructive sleep apnea is a serious health issue affecting more than one billion people worldwide. Although continuous positive airway pressure is the mainstay for the treatment of obstructive sleep apnea, hypoglossal nerve stimulation is a surgical option for patients who are unable to tolerate or adhere to this therapy. As more hypoglossal nerve stimulators are implanted, these patients will present with increasing frequency for medical procedures requiring general anesthesia or deep sedation. We describe our experience with one such patient and hope this information can be used to develop future guidelines to aid in the anesthetic management of these patients.

Hypoventilation Syndrome Secondary to Club-Shaped Chest Wall Deformity.

Hypoventilation syndrome is defined as a decrease in alveolar ventilation leading to hypercapnia (PaCO2 > 35-45 mmHg) and hypoxemia. There are multiple causes of hypoventilation syndrome described in the literature, of which central and obesity-related causes are more prevalent. Other causes such as neuromuscular disorders and chest wall deformities are relatively less common. Multiple defects in the normal functioning of the respiratory function are implicated in the pathophysiological mechanism of hypoventilation syndrome, such as a hypoactive central ventilatory drive, decreased airway function, ventilation-perfusion mismatch, defective pulmonary mechanics, and respiratory muscle fatigue. Patients often present with dyspnea, headache, lethargy, repeated pulmonary infections, hypoxia that usually improves with low flow oxygen, and hypercapnia that may alter mental function. Nocturnal or diurnal assisted mechanical ventilation is proven to be an effective therapy for patients suffering hypoventilation syndromes. We describe a case of a 47-year-old woman with hypoventilation syndrome resulting from a rare chest wall deformity with inward protrusion of the costochondral junction of the ribs with ossification of the costal cartilage on CT who presented with dyspnea and hypercapnia.

A Case of Medullary Infarct Causing Central Alveolar Hypoventilation.

Central alveolar hypoventilation (CAH) is a rarely encountered pathology characterized by decreased ventilation due to the loss of autonomic control. Most cases present at birth, as it can be a rare genetic disorder, but we aim to show that it can occur as an acquired condition too. We present a case of a 65-year-old man who developed CAH as a sequela of an ischemic stroke and discuss possible pathophysiology. Increasing awareness and an early detection of this condition can have a significant effect on morbidity and mortality of patients.

Sleep-disordered breathing and its management in children with rare skeletal dysplasias.

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

Disorders of sleep in spinal and bulbar muscular atrophy (Kennedy's disease).

INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is a progressive, X-linked lower motor neuron disorder exclusively affecting men. Since knowledge on sleep disorders in SBMA is scarce compared to other motoneuron diseases, this retrospective case-control study aimed to investigate sleep and sleep-related breathing in patients with SBMA. METHODS: In 23 non-ventilated patients with SBMA (median age 52 years), clinical disease characteristics, forced vital capacity and diagnostic polysomnographies were retrospectively evaluated. In 16 patients, overnight transcutaneous capnometry was available. Twenty-three male control subjects with chronic insomnia were matched for age and body mass index. RESULTS: In patients with SBMA obstructive sleep apnoea (OSA, apnoea-hypopnoea index/AHI > 5/h) was more frequent than in control subjects (14/23 or 61% vs. 6/23 or 26%, p = 0.02), and median AHI was significantly higher in patients (9.0/h vs. 3.4/h, p < 0.01). Among SBMA patients, the AHI was not related to age or body mass index. Alveolar hypoventilation as reflected by nocturnal hypercapnia was found in 3/16 patients. Rapid eye movement (REM) sleep without atonia was present in 44% of SBMA patients but only in 4% of controls (p < 0.01). During REM and non-REM sleep, no behavioural abnormalities were observed in either group. Periodic limb movements in sleep (index > 15/h) were frequent in SBMA patients but rarely disrupted sleep. CONCLUSIONS: In patients with SBMA, sleep-disordered breathing may comprise both OSA and nocturnal hypoventilation. REM sleep without atonia may also be found, but its clinical significance remains unclear. In patients complaining of sleep-related symptoms, cardiorespiratory polysomnography and transcutaneous capnometry are recommended.

Evolution of Pediatric Home Mechanical Ventilation Program in Serbia-What Has Changed in the Last Decade.

Home mechanical ventilation (HMV) is a method of treatment in children with sleep-disordered breathing (SDB) and alveolar hypoventilation regardless of primary disease. The goal of the study was to describe the changes in the HMV program in Serbia during the last two decades. Cross-sectional retrospective study included data from the national HMV database from 2001 until 2019. HMV was initiated in clinically stable patients after the failure to wean from mechanical ventilation succeeded acute respiratory deterioration or electively after the confirmation of SDB and alveolar hypoventilation by sleep study or continuous transcutaneous capnometry and oximetry. The study included 105 patients (50 ventilated noninvasively and 55 ventilated invasively via tracheostomy). The median age at the time of HMV initiation was 6.2 years (range: 0.3-18 years). Invasive ventilation had been initiated significantly earlier than noninvasive ventilation (NIV) (p < 0.01), without difference in duration of ventilatory support (p = 0.95). Patients on NIV were significantly older (p < 0.01) than those ventilated invasively (13 and 1.5 years, respectively). Average waiting time on equipment had been shortened significantly-from 6.3 months until 2010 to 1 month at the end of the study (p < 0.01). Only 6.6% of patients had obstructive sleep apnea syndrome (OSAS) requiring HMV. During the study period, 24% patients died, mostly due to uncontrolled infection or progression of underlying disease. Availability and shortened waiting time for the equipment accompanied by advanced overall health care led to substantial improvements in the national HMV program. However, future improvements should be directed to systematic evaluation of SDB in patients with OSAS, early diagnosis of nocturnal hypoventilation, and subsequent timely initiation of chronic ventilation.

Respiratory manifestations in inherited metabolic diseases: 6-year single-center experience.

OBJECTIVES: We aimed to call attention to respiratory system manifestations which occur in the course of many inherited metabolic diseases (IMD), and present as the leading cause of death. MATERIALS AND METHODS: We retrospectively reviewed the diagnosis, treatment, and outcome of patients evaluated at our hospital between June 2012 and June 2018 with a diagnosis of IMD and accompanying respiratory manifestations. RESULTS: A total of 50 children (29 [58%] male, 21 [42%] female) with IMD and respiratory manifestations were defined. Disorders of intracellular metabolism (n = 33, 66%) formed the majority, followed by intoxication type metabolic disorders (n = 9, 18%) and energy metabolism disorders (n = 8, 16%). The most frequent respiratory symptoms were snoring (20, 40%), tachypnea (16, 32%) and wheezing (14, 28%). Physical examination findings were signs of respiratory distress (n = 28, 56%), crackles (n = 24, 48%), thoracic deformity (n = 23, 46%), decreased breath sounds (n = 17, 34%), rhonchus (n = 17, 34%), wheezing (n = 17, 34%) and stridor (n = 10, 20%). Major respiratory manifestations were chronic airway aspiration (n = 23, 46%), upper airway obstruction (n = 23, 46%), and recurrent pneumonia (n = 18, 36%). Twenty-three 23 patients (46%) experienced endotracheal intubation, 9 patients (18%) required whole-house mechanical ventilation and tonsilloadenoidectomy was performed in 7 patients (14%). Overall survival rate was 70% (n = 35) in a median follow-up period of 2.36 (0.05-5.86) years. CONCLUSIONS: Respiratory system manifestations of IMD strongly relate with increased morbidity and mortality. Therefore, prompt diagnosis and correct intervention of respiratory complications with a multidisciplinary team including pediatric metabolic diseases specialists, pulmonologists, otorhinolaryngologists, physiotherapists, and anesthesiologists are crucial to prevent progression and irreversible damage.

Congenital central hypoventilation syndrome: diagnosis and management.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare disorder defined by a failure in autonomic control of breathing secondary to mutations of the PHOX2B gene. Affected individuals demonstrate absent or diminished physiologic response to hypercapnia and hypoxia that is most severe during sleep as well as multi-system dysregulation of autonomic functions. Areas covered: In this review, we will discuss how evaluation of the disease-defining PHOX2B gene aids diagnosis and helps prognosticate disease severity, review disease physiology, describe clinical presentation and various aspects of autonomic nervous system dysregulation, review ventilatory strategies, and highlight current challenges in the care of these complex patients. Expert commentary: CCHS is a rare disorder that requires a high degree of vigilance. PHOX2B mutation is essential for diagnosis and also helps direct disease management. There is currently no pharmacologic treatment proven effective in improving disease-related hypoventilation and care is focused on providing adequate ventilatory support and managing autonomic dysfunction.

Initiation of Noninvasive Ventilation for Sleep Related Hypoventilation Disorders: Advanced Modes and Devices.

Although noninvasive ventilation (NIV) has been used since the 1950s in the polio epidemic, the development of modern bilevel positive airway pressure (BPAP) devices did not become a reality until the 1990s. Over the past 25 years, BPAP technology options have increased exponentially. The number of patients receiving this treatment both in the acute setting and at home is growing steadily. However, a knowledge gap exists in the way the settings on these devices are adjusted to achieve synchrony and match the patient's unique physiology of respiratory failure. This issue is further complicated by differences in pressure and flow dynamic settings among different types of NIV devices available for inpatient and home care.

Pulmonary Hypertension and Its Response to Treatment in a Patient with Kyphosis-related Alveolar Hypoventilation.

Pulmonary hypertension (PH) with kyphoscoliosis-related alveolar hypoventilation is uncommon, so little is known about the effectiveness of treatments for this condition. A 66-year-old man with kyphosis who had been treated with nocturnal noninvasive positive-pressure ventilation developed PH with a mean pulmonary arterial pressure (PAP) of 32 mmHg and a pulmonary vascular resistance (PVR) of 5.95 Wood units. After addition of oxygen therapy and tadalafil, his condition improved. One year later, his mean PAP and PVR were 25 mmHg and 3.62 Wood units, respectively. This case shows the therapeutic potential of vasoactive medications for alveolar hypoventilation-related PH.