Tracheostomy and inpatient outcomes among children with congenital central hypoventilation syndrome: A kids' inpatient database study.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a rare disease predisposing children to respiratory failure due to abnormal ventilatory drive. Variability in hypoventilation and respiratory support need have been reported. We aim to identify clinical variables associated with incident tracheostomy and common etiologies of hospitalization among children with CCHS. METHODS: Hospital discharge records were obtained for children (<21 years) with CCHS hospitalized between 2006 and 2019 from the Kid's Inpatient Database. Primary diagnostic categories for hospitalizations with CCHS were summarized. Multivariable logistic regression models were used to explore risk factors associated with incident tracheostomy. RESULTS: Among 2404 hospitalizations with CCHS, 133 (5.5%) had incident tracheostomy, 1230 (51.2%) had established tracheostomy, and 1041 (43.3%) had no tracheostomy. Compared with children without tracheostomy, those with incident tracheostomy were younger, had a history of prematurity, congenital heart disease, laryngeal, glottic, and subglottic stenosis (LGSS), congenital airway anomalies, neuromuscular weakness, gastroesophageal reflux disease. Children without tracheostomy had higher mortality than those with tracheostomy status (2.19% vs. 0.66%). Multivariable-adjusted analyses showed that incident tracheostomy was associated with infancy (0-1 years), neuromuscular weakness, and congenital heart disease. Most common diagnostic categories include (1) diseases of the respiratory system (30.23%), (2) injury and poisoning (9.35%), and (3) diseases of the nervous system and sense organs (6.71%). CONCLUSIONS: Children with CCHS who received incident tracheostomy are more likely to be younger and with LGSS, neuromuscular weakness and congenital heart disease. Clinicians should be aware of these risk factors representing more severe CCHS with earlier manifestation needing tracheostomy. Higher mortality among nontracheostomy group highlights the need for considering tracheostomy in caring for children with CCHS.

Respiratory comorbidities and treatments in Duchenne muscular dystrophy: impact on life expectancy and causes of death.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. METHODS: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. RESULTS: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. CONCLUSIONS: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.

Nocturnal Hypoventilation in the Patients Submitted to Thoracic Surgery.

Introduction: Nocturnal hypoventilation may occur due to obesity, concomitant chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and/or the use of narcotic analgesics. The aim of the study was to evaluate the risk and severity of nocturnal hypoventilation as assessed by transcutaneous continuous capnography in the patients submitted to thoracic surgery. Materials and Methods: The material of the study consisted of 45 obese (BMI 34.8 ± 3.7 kg/m2) and 23 nonobese (25.5 ± 3.6 kg/m2) patients, who underwent thoracic surgery because of malignant (57 patients) and nonmalignant tumors. All the patients received routine analgesic treatment after surgery including intravenous morphine sulfate. Overnight transcutaneous measurements of CO2 partial pressure (tcpCO2) were performed before and after surgery in search of nocturnal hypoventilation, i.e., the periods lasting at least 10 minutes with tcpCO2 above 55 mmHg. Results: Nocturnal hypoventilation during the first night after thoracic surgery was detected in 10 patients (15%), all obese, three of them with COPD, four with high suspicion of moderate-to-severe OSA syndrome, and one with chronic daytime hypercapnia. In the patients with nocturnal hypoventilation, the mean tcpCO2 was 53.4 ± 6.1 mmHg, maximal tcpCO2 was 59.9 ± 8.4 mmHg, and minimal tcpCO2 was 46.4 ± 6.7 mmHg during the first night after surgery. In these patients, there were higher values of minimal, mean, and maximal tcpCO2 in the preoperative period. Nocturnal hypoventilation in the postoperative period did not influence the duration of hospitalization. Among 12 patients with primary lung cancer who died during the first two years of observation, there were 11 patients without nocturnal hypoventilation in the early postoperative period. Conclusion: Nocturnal hypoventilation may occur in the patients after thoracic surgery, especially in obese patients with bronchial obstruction, obstructive sleep apnea, or chronic daytime hypercapnia, and does not influence the duration of hospitalization.

Sleep apnoea and hypoventilation in patients with five major types of muscular dystrophy.

BACKGROUND: The characteristics of and relationship between sleep apnoea and hypoventilation in patients with muscular dystrophy (MD) remain to be fully understood. METHODS: We analysed 104 in-laboratory sleep studies of 73 patients with MD with five common types (DMD-Duchenne, Becker MD, CMD-congenital, LGMD-limb-girdle and DM-myotonic dystrophy). We used generalised estimating equations to examine differences among these types for outcomes. RESULTS: Patients in all five types had high risk of sleep apnoea with 53 of the 73 patients (73%) meeting the diagnostic criteria in at least one study. Patients with DM had higher risk of sleep apnoea compared with patients with LGMD (OR=5.15, 95% CI 1.47 to 18.0; p=0.003). Forty-three per cent of patients had hypoventilation with observed prevalence higher in CMD (67%), DMD (48%) and DM (44%). Hypoventilation and sleep apnoea were associated in those patients (unadjusted OR=2.75, 95% CI 1.15 to 6.60; p=0.03), but the association weakened after adjustment (OR=2.32, 95% CI 0.92 to 5.81; p=0.08). In-sleep average heart rate was about 10 beats/min higher in patients with CMD and DMD compared with patients with DM (p=0.0006 and p=0.02, respectively, adjusted for multiple testing). CONCLUSION: Sleep-disordered breathing is common in patients with MD but each type has its unique features. Hypoventilation was only weakly associated with sleep apnoea; thus, high clinical suspicion is needed for diagnosing hypoventilation. Identifying the window when respiratory muscle weakness begins to cause hypoventilation is important for patients with MD; it enables early intervention with non-invasive ventilation-a therapy that should both lengthen the expected life of these patients and improve its quality.Cite Now.

Hypoventilation in the PACU is associated with hypoventilation in the surgical ward: Post-hoc analysis of a randomized clinical trial.

OBJECTIVE: To evaluate the association between early postoperative hypoventilation in the last hour of the post-anesthesia care unit (PACU) stay and hypoventilation during the rest of the first 48 postoperative hours in the surgical ward. DESIGN: Sub-analysis of a clinical trial. SETTING: PACU and surgical wards of a single medical center. PATIENTS: Adults having abdominal surgery under general anesthesia. INTERVENTIONS: Monitoring with a respiratory volume monitor from admission to PACU until the earlier of 48 h after surgery or discharge. MEASUREMENTS: The exposure was having at least one low minute-ventilation (MV) event during the last hour of PACU stay, defined as MV lower than 40% the predicted value lasting at least 1 min. The primary outcome was low MV events lasting at least 2 min during the rest of the first 48 postoperative hours, while in the surgical ward. The secondary outcome was the rate of low MV events per monitored hour. MAIN RESULTS: Data of 292 patients were analyzed, of which 20 (6.8%) patients had a low MV event in PACU. Low MV events in the surgical ward were found in 81 (28%) patients. All patients who had low MV events in PACU had events again in the ward, while 61/272 (22%) had an event in the ward but not in PACU. The incidence rate of low MV events per hour was 24 (95% CI: 13, 46) among patients having an event in the PACU, and 2 (1, 4) among those who did not. CONCLUSIONS: In adults recovering from abdominal surgery, events of hypoventilation during the first postoperative hour are associated with similar events during the rest of the first 48 postoperative hours, with positive predictive value approaching 100%. Sixty-one patients had ward hypoventilation that was not preceded by hypoventilation in PACU.

Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease.

Purpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH. Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH. Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16-6.00] and 11.1 [95% CI: 1.39-87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04-2.64] and 6.6 [95% CI: 1.06-39.4], respectively. Conclusion: In patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.

Sleep disordered breathing (SDB) in neonates and implications for its long-term impact.

Sleep-disordered breathing (SDB) is a significant cause of morbidity in neonates and young infants. SDB occurs more commonly in preterm infants and in neonates with underlying syndromes. Recent evidence shows that infants with obstructive sleep apnoea (OSA) or SDB have greater health care resource utilization, including longer hospital stay. Management of SDB includes non-invasive ventilation or surgical interventions tailored to the patient. Screening high risk newborns should allow for early diagnosis and timely therapeutic intervention for this population. However, the thresholds for diagnosing SDB and for guiding and implementing treatment in neonates remain unclear. A collective effort is required to standardize the practice worldwide. This article will discuss neonatal sleep physiology and characteristics of neonatal sleep, with an emphasis on the epidemiology and diagnosis of SDB in neonates and its implications for long term outcomes.

Causative and common PHOX2B variants define a broad phenotypic spectrum.

Paired Like homeobox 2B (PHOX2B) is a gene crucial for the differentiation of the neural lineages of the autonomic nervous system (ANS), whose coding mutations cause congenital central hypoventilation syndrome (CCHS). The vast majority of PHOX2B mutations in CCHS is represented by expansions of a polyalanine region in exon 3, collectively defined PARMs (PolyAlanine Repeat Mutations), the minority being frameshift, missense and nonsense mutations, defined as NPARMs (Non-PARMs). While PARMs are nearly exclusively associated with isolated CCHS, most of NPARMs is detected in syndromic CCHS, presenting with neuroblastoma and/or Hirschsprung disease. More recently, evidence of a complex role of PHOX2B in the pathogenesis of a wider spectrum of ANS disorders has emerged. Indeed, common and hypomorphic PHOX2B variants, including synonymous, polyalanine-contractions, gene deletions may influence the occurrence of either apparent life-threatening event (ALTE), Sudden Infant Death Syndrome (SIDS), neuroblastoma, or isolated HSCR, likely through small effects on PHOX2B expression levels. After an introduction to the role of PHOX2B in the ANS development, causative mutations, common variants, and gene expression deregulation of the PHOX2B gene are discussed, though the involvement of synonymous variants and contractions requires further confirmations with respect to ANS disorders and molecular mechanisms underlying the PHOX2B phenotypic heterogeneity.

Influence of ß2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.

Sleep in chronic respiratory disease: COPD and hypoventilation disorders.

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

Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases.

Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression "Ondine's Curse", is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung's Disease or neural crest tumours). CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

Predicting effective remifentanil concentration in 95% of patients to prevent emergence cough after laryngomicroscopic surgery.

Smooth emergence or cough prevention is a clinically important concern in patients undergoing laryngomicroscopic surgery (LMS). The purpose of this study was to estimate the effective concentration of remifentanil in 95% of patients (EC95) for the prevention of emergence cough after LMS under propofol anesthesia using the biased coin design (BCD) up-down method.A total of 40 adult patients scheduled to undergo elective LMS were enrolled. Anesthesia induction and maintenance were performed with target-controlled infusion of propofol and remifentanil. Effective effect-site concentration (Ce) of remifentanil in 95% of patients for preventing emergence cough was estimated using a BCD method (starting from 1 ng/mL with a step size of 0.4 ng/mL). Hemodynamic and recovery profiles were observed after anesthesia.According to the study protocol, 20 patients were allocated to receive remifentanil Ce of 3.0 ng/mL, and 20 patients were assigned to receive lower concentrations of remifentanil, from 1.0 to 2.6 ng/mL. Based on isotonic regression with a bootstrapping method, EC95 (95% CI) of remifentanil Ce for the prevention of emergence cough from LMS was found to be 2.92 ng/mL (2.72-2.97 ng/mL). Compared with patients receiving lower concentrations of remifentanil, the incidence of hypoventilation before extubation and extubation time were significantly higher in those receiving remifentanil Ce of 3.0 ng/mL. However, hypoventilation incidence after extubation and staying time in the recovery room were comparable between the 2 groups.Using a BCD method, the EC95 of remifentanil Ce for the prevention of emergence cough was estimated to be 2.92 ng/mL (95% CI: 2.72-2.97 ng/mL) after LMS under propofol anesthesia.

Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis.

OBJECTIVE: This retrospective study aimed to investigate whether overnight oxymetry and early morning blood gas analysis predict nocturnal hypoventilation (NH) as reflected by night-time hypercapnia in patients with amyotrophic lateral sclerosis (ALS). In addition, prevalence and clinical determinants of sleep apnoea in ALS were evaluated. METHODS: In 250 patients with non-ventilated ALS, transcutaneous capnometry was performed along with polysomnography or polygraphy and early morning blood gases. RESULTS: 123 patients were female, and 84 patients had bulbar-onset ALS. 40.0% showed NH, and an apnoea-hypopnoea index (AHI) >5/hour was found in 45.6%. In 22.3%, sleep apnoea and NH coincided. The obstructive apnoea index was significantly higher than the central apnoea index (p<0.0001). Both NH and sleep apnoea were significantly more common in male than in female patients. Sleep apnoea and AHI were associated with better bulbar function. Desaturation time (t<90%) and transcutaneous CO2 were negatively correlated with upright vital capacity. Early morning base excess (EMBE), bicarbonate and t<90% were independent predictors of NH. However, among 100 patients with NH, 31 were missed by t<90% >5 min and 17 were not identified when EMBE >3 mmol/L and t<90% >5 min were combined. CONCLUSION: In ALS, sleep apnoea is common and often accompanies NH. It is mainly obstructive, and central apnoea appears to be clinically irrelevant. Polygraphy or oxymetry alone are not sufficient to uncover NH. Combination of EMBE and t<90% may increase sensitivity, but transcutaneous capnography is strongly recommended for reliable detection of NH in patients with ALS.

Non-anesthesiologist-administered propofol is not related to an increase in transcutaneous co2 pressure during flexible bronchoscopy compared to guideline-based sedation: a randomized controlled trial / La administración de propofol por parte de no anestesiólogos durante la broncoscopia flexible no se relaciona con aumentos de la presión transcutánea de CO2, en comparación con la sedación según las pautas: ensayo controlado aleatorizado

Introduction: Evidence for the use of non-anesthesiologist-administered propofol for sedation during flexible bronchoscopy is scarce. The main objective of this study was to determine whether non-anesthesiologist-administered propofol balanced sedation was related to higher transcutaneous CO2 pressure compared with current guideline-based sedation (combination midazolam and opioid). Secondary outcomes were post-procedural recuperation time, patient satisfaction and frequency of adverse events. Methods: In this randomized controlled trial we included data from outpatients aged 18 years or older with an indication for flexible bronchoscopy in a university hospital in northern Mexico. Results: Ninety-one patients were included: 42 in the midazolam group and 49 in the propofol group. During 60min of transcutaneous capnometry monitoring, mean transcutaneous CO2 pressure values did not differ significantly between groups (43.6 [7.5] vs. 45.6 [9.6]mmHg, P=.281). Propofol was related with a high Aldrete score at 5, 10, and 15min after flexible bronchoscopy (9 [IQR 6-10] vs. 10 [9,10], P=.006; 9 [8-10] vs. 10 [IQR 10-10], P<.001 and 10 [IQR 9-10] vs. 10 [10], respectively) and with high patient satisfaction on a visual analogue scale of 1 (not satisfied) to 10 (very satisfied) (8.41 [1.25] vs. 8.97 [0.98], P=.03). Frequency of adverse events was similar among groups (30.9% vs. 22.4%, P=.47). Conclusion: Compared with guideline-recommended sedation, non-anesthesiologist-administered propofol balanced sedation is not associated with higher transcutaneous CO2 pressure or with more frequent adverse effects. Propofol use is associated with faster sedation recovery and with high patient satisfaction (AU)

Introducción: Las pruebas disponibles del uso de propofol administrado por no anestesiólogos para la sedación durante la broncoscopia flexible son escasas. El objetivo principal del estudio fue determinar si la sedación equilibrada con propofol administrado por no anestesiólogos estaba relacionada con valores más altos de presión de CO2 transcutánea, en comparación con la sedación según las pautas (una combinación de midazolam y un opiáceo). Las variables secundarias fueron el tiempo de recuperación después del procedimiento, el grado de satisfacción del paciente y la frecuencia de observación de efectos adversos. Métodos: En este ensayo controlado y aleatorizado se incluyeron datos de pacientes ambulatorios mayores de 18 años con indicación de broncoscopia flexible en un hospital universitario del norte de México. Resultados: Se incluyeron 91 pacientes: 42 en el grupo de midazolam y 49 en el grupo de propofol. Durante los 60 min de monitorización de la capnometría transcutánea, no hubo diferencias estadísticamente significativas entre grupos en los valores medios de presión de CO2 transcutánea (43,6 [5,7] vs. 45,6 [6,9]mm Hg, p=0,281). El propofol se asoció con puntuaciones de Aldrete altas a los 5, 10 y 15min después de la broncoscopia flexible (9 [IQR: 6-10] vs. 10 [9,10], p=0,006; 9 [8-10] vs. 10 [IQR 10-10], p<0,001 y 10 [IQR 9-10] vs. 10 [10] puntos, respectivamente) y con un alto grado de satisfacción de los pacientes en una escala visual de 1 (poco satisfecho) a 10 (muy satisfecho) (8,41 [1,25] vs. 8,97 [0,98], p=0,03). No hubo diferencias en la frecuencia de efectos adversos (30,9 vs. 22,4%, p=0,47). Conclusión: En comparación con la pauta de sedación recomendada, la sedación equilibrada con propofol administrado por no anestesiólogos no se asocia con valores más altos de presión de CO2 transcutánea ni con mayor frecuencia de efectos adversos. El uso del propofol se asocia con una recuperación de la sedación más rápida y con un mayor grado de satisfacción del paciente (AU)

Pacientes españoles con síndrome de hipoventilación central incluidos en el Registro europeo. Datos del 2015 / Spanish patients with central hypoventilation syndrome included in the European Registry. The 2015 data

INTRODUCCIÓN: El síndrome de hipoventilación central congénita (SHCC) es una enfermedad genética muy rara causada por mutaciones en PHOX2B; en 2010 se creó el Consorcio Europeo del Síndrome de Hipoventilación Central, que en 2012 implantó un Registro online de pacientes para optimizar su cuidado. OBJETIVO: Conocer las características y la evolución de los pacientes españoles con SHCC y detectar áreas de mejora. MATERIALES Y MÉTODO: Se analizaron los datos actualizados en diciembre del 2015 de los pacientes españoles del Registro europeo. RESULTADOS: Se registró a 38 pacientes, nacidos entre 1987 y 2013, procedentes de 18 hospitales. El 34,2% eran mayores de 18 años. Han fallecido 3 pacientes. Aportaban estudio del gen PHOX2B 37 (97,3%), 32 (86,5%) con mutación. Los genotipos 20/25, 20/26 y 20/27 representaron el 84,3% de las mutaciones. Las disautonomías fueron más frecuentes y graves en portadores de genotipos con mayores expansiones de polialaninas. El 47% de pacientes asociaba alteraciones oculares, el 16% Hirschsprung, el 13% hipoglucemias y el 5% tumores. Treinta pacientes (79%) debutaron en el periodo neonatal y 8 (21%) posteriormente (inicio/diagnóstico tardío). Ocho niños (21%) recibieron inicialmente ventilación domiciliaria con mascarilla; 5 eran lactantes con comienzo neonatal, 2 de ellos precisaron cambio a traqueostomía tras presentar parada cardiorrespiratoria; ambos tenían mutaciones graves. Han sido decanulados y transferidos a mascarilla el 34,3% de los pacientes (edad media: 13,7 años). El 29,4% de los niños escolarizados precisaron refuerzo educativo. CONCLUSIÓN: La implementación del Registro en España de pacientes con SHCC ha permitido identificar aspectos relevantes para optimizar sus cuidados, tales como la importancia del estudio genético para el diagnóstico y la estimación de gravedad, la frecuencia elevada de alteraciones oculares y de necesidad de refuerzo educativo, y algunas limitaciones de las técnicas ventilatorias

INTRODUCTION: Congenital Central Hypoventilation Syndrome (CCHS) is a very rare genetic disease. In 2012 the European Central Hypoventilation Syndrome (EuCHS) Consortium created an online patient registry in order to improve care. AIM: To determine the characteristics and outcomes of Spanish patients with CCHS, and detect clinical areas for improvement. MATERIALS AND METHOD: An assessment was made on the data from Spanish patients in the European Registry, updated on December 2015. RESULTS: The Registry contained 38 patients, born between 1987 and 2013, in 18 hospitals. Thirteen (34.2%) were older than 18 years. Three patients had died. Genetic analysis identified PHOX2B mutations in 32 (86.5%) out of 37 patients assessed. The 20/25, 20/26 and 20/27 polyalanine repeat mutations (PARMs) represented 84.3% of all mutations. Longer PARMs had more, as well as more severe, autonomic dysfunctions. Eye diseases were present in 47%, with 16% having Hirschsprung disease, 13% with hypoglycaemia, and 5% with tumours. Thirty patients (79%) required ventilation from the neonatal period onwards, and 8 (21%) later on in life (late onset/presentation). Eight children (21%) were using mask ventilation at the first home discharge. Five of them were infants with neonatal onset, two of them, both having a severe mutation, were switched to tracheostomy after cardiorespiratory arrest at home. Approximately one-third (34.3%) of patients were de-cannulated and switched to mask ventilation at a mean age of 13.7 years. Educational reinforcement was required in 29.4% of children attending school. CONCLUSION: The implementation of the EuCHS Registry in Spain has identified some relevant issues for optimising healthcare, such as the importance of genetic study for diagnosis and assessment of severity, the high frequency of eye disease and educational reinforcement, as well as some limitations in ventilatory techniques

Sleep-Related Breathing Disorders in Chiari Malformation Type 1: A Prospective Study of 90 Patients.

Study objective: The aim of the present study is to describe the prevalence of sleep disorders in a large group of patients with Chiari malformation type 1 (CM-1) and determine the presence of risk factors associated with these abnormalities. Methods: Prospective study with consecutive patient selection. We included 90 adult patients with CM-1, defined by the presence of a cerebellar tonsillar descent (TD) ≥3 mm. Clinical, neuroradiological studies, and nocturnal polysomnography (PSG) was carried out. In addition, patients were also subclassified into 2 CM subtypes: CM-1, with the obex above the foramen magnum (FM) and CM-1.5, in which along with a TD ≥3 mm, the obex was located below the FM. Results: We observed a high prevalence (50%) of sleep-related breathing disorders (SRBDs) with predominant hypopnea. Only six patients showed a central apnea index of ≥5. Hypoventilation was observed in only three patients. SRBD severity was associated with male sex, older age, excess weight, and the presence of hydrocephalus. No differences in clinical or PSG parameters were found when comparing CM subtypes (CM-1 and CM-1.5). Sleep architecture study showed decreased sleep efficiency with an increase in arousal and waking after sleep onset. The presence of SRBDs was found to be associated with poorer sleep architecture parameters. Conclusions: This study confirms a high prevalence of SRBDs in patients with CM-1 and CM-1.5, with a predominant obstructive component. Nocturnal PSG recordings should be systematically conducted in these patients, especially those who are male, older, or overweight or those who present hydrocephalus.

Social and Economic Impacts of Managing Sleep Hypoventilation Syndromes.

Hypoventilation during sleep is often an early indicator of the development of respiratory failure. Alterations in ventilation are more pronounced during sleep and often present before the onset of daytime symptoms. This article discusses the most common sleep-related hypoventilatory disorders and recommended treatment approaches for obesity hypoventilation, chronic obstructive pulmonary disease, and neuromuscular disorders. Accurate diagnosis and appropriate treatment is of paramount importance because of the impact on individual health outcomes and overall cost of health care delivery. Appropriate treatment is successful at reducing hospitalizations and health care costs as well as improving quality of life and individual economic burden.

[Spanish patients with central hypoventilation syndrome included in the European Registry. The 2015 data]. / Pacientes españoles con síndrome de hipoventilación central incluidos en el Registro europeo. Datos del 2015.

INTRODUCTION: Congenital Central Hypoventilation Syndrome (CCHS) is a very rare genetic disease. In 2012 the European Central Hypoventilation Syndrome (EuCHS) Consortium created an online patient registry in order to improve care. AIM: To determine the characteristics and outcomes of Spanish patients with CCHS, and detect clinical areas for improvement. MATERIALS AND METHOD: An assessment was made on the data from Spanish patients in the European Registry, updated on December 2015. RESULTS: The Registry contained 38 patients, born between 1987 and 2013, in 18 hospitals. Thirteen (34.2%) were older than 18 years. Three patients had died. Genetic analysis identified PHOX2B mutations in 32 (86.5%) out of 37 patients assessed. The 20/25, 20/26 and 20/27 polyalanine repeat mutations (PARMs) represented 84.3% of all mutations. Longer PARMs had more, as well as more severe, autonomic dysfunctions. Eye diseases were present in 47%, with 16% having Hirschsprung disease, 13% with hypoglycaemia, and 5% with tumours. Thirty patients (79%) required ventilation from the neonatal period onwards, and 8 (21%) later on in life (late onset/presentation). Eight children (21%) were using mask ventilation at the first home discharge. Five of them were infants with neonatal onset, two of them, both having a severe mutation, were switched to tracheostomy after cardiorespiratory arrest at home. Approximately one-third (34.3%) of patients were de-cannulated and switched to mask ventilation at a mean age of 13.7 years. Educational reinforcement was required in 29.4% of children attending school. CONCLUSION: The implementation of the EuCHS Registry in Spain has identified some relevant issues for optimising healthcare, such as the importance of genetic study for diagnosis and assessment of severity, the high frequency of eye disease and educational reinforcement, as well as some limitations in ventilatory techniques.

Safety of unsedated PEG placement using transoral ultrathin endoscopy in patients with amyotrophic lateral sclerosis.

BACKGROUND AND AIMS: In patients with amyotrophic lateral sclerosis (ALS), percutaneous endoscopic gastrostomy (PEG) placement under sedation often causes apnea or hypoventilation. The aim of the present study was to assess whether unsedated PEG placement in ALS patients using ultrathin endoscopy (UTE) via the transoral route can improve safety. METHODS: Between 2003 and 2013, PEG placement was identified and reviewed in 45 patients with ALS. PEG was performed in 14 patients using transoral UTE without sedation (UTE group), 17 patients using conventional normal-diameter esophagogastroduodenoscopy (C-EGD) without sedation (unsedated C-EGD group) and 14 patients using C-EGD with sedation (sedated C-EGD group). We compared the clinical features, cardiopulmonary data before and during PEG placement, and complications related to PEG placement among the three groups. RESULTS: There were no significant differences in age, male/female ratio, forced vital capacity, blood pressure, oxygen saturation before and during PEG, or major complications among the three groups. No minor complications were observed in the UTE group, whereas apnea and/or hypoventilation were observed in the sedated C-EGD group and aspiration pneumonia was observed in the unsedated C-EGD group. CONCLUSIONS: Unsedated PEG placement using transoral UTE in ALS patients is a safe method.

Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature.

Congenital central hypoventilation syndrome (CCHS) is a form of sleep-disordered breathing characterized by a diminished drive to breathe during sleep, despite progressive hypercapnia and hypoxia. The condition results from mutations in the paired-like homeobox 2B (PHOX2B) gene. The aim of this review was to conduct a systematic search of the current data on CCHS as it relates to perioperative considerations and to discuss the classification, prevalence, pathophysiology, presentation, genetics, and management of the condition. A systematic search of Medline, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials was done up to October 2015. The results were limited to human studies published in the English language. Study titles and abstracts were screened to identify studies relating to CCHS relevant to anesthetic care. All study designs including randomized controlled trials, observational studies, case reports, or case series were included. The searches yielded 165 articles, of which 45 were relevant to perioperative considerations. There were 15 relevant case reports categorized as pertaining to the following: (1) novel presentations of the condition after sedation/anesthesia; (2) anesthetic techniques used in patients with established CCHS; and (3) patients with CCHS who experienced anesthetic complications. Review of the case reports showed that patients ranged from neonates up to 59 years of age. Novel presentations of the disease after sedation or anesthesia for minor procedures often led to diagnosis. The sequelae of undiagnosed CCHS led to complications, such as hypoxia, desaturations, apneas, seizures, unplanned intensive care admissions, prolonged hospital stays, and long-term tracheostomies. There appeared to be few postoperative complications in patients with known CCHS. Anesthesiologists need to be aware of undiagnosed late-onset CCHS and include this condition in the differential diagnosis of patients with unexplained postoperative respiratory depression. Anesthetic techniques should minimize the use of agents that further depress respiration postprocedure and ensure adequate monitoring to detect postoperative apneas.