Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis

Abstract Objective Summarize the evidence on drug therapies for obstructive sleep apnea. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. Results 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. Conclusion The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO registration number CRD42022362639.

CPAP Pressure Prediction Calculation. An Alternative to the Difficulty of Performing a Titration Within the Context of the COVID19 Pandemic

Abstract Introduction: The treatment of choice for the obstructive sleep apnea-hypopnea syndrome (OSAHS) is continuous positive air pressure in the airway (CPAP), titrating the effective pressure that eliminates obstructive events through validated methods. From the beginning of the COVID 19 pandemic, it has been recommended that conventional titration should be postponed, replacing it with self-adjusting equipment. In our population, access to these devices is difficult. Objective: To show whether there is a difference between the CPAP pressure level calculated through a prediction formula and the pressure determined by titration under polysomnography. Materials and Methods: We included patients with OSAHS who underwent effective CPAP titration and compared it with the cal culated CPAP by the Miljeteig and Hoffstein formula. Results: We included medical records of 583 patients, (56%) men, 51 years (41-61), apnea-hypopnea index (AHI) of 51.3 (29.2 -84.4), calculated CPAP, 9.3 cm H2O vs. effective CPAP, 8 cm H2O (p < 0.0001). Comparing according to the degree of severity of the OSAHS, the average difference between calculated CPAP and effective CPAP was 0.24, 0.21, and 0.41 (non-significant differences) for mild, moderate and severe, up to an AHI < 40; in patients with an AHI ≥ 40 this difference was 1.10 (p < 0.01). We found an ac ceptable correlation between the calculated CPAP and the effective CPAP, with an intraclass correlation coefficient of 0.621, p < 0.01. Conclusion: We could use CPAP pressure prediction calculations to start treatment in patients with OSAHS who don't have access to self-adjusting therapies within the context of the pandemic, until standard calibration measures can be taken.

Hipertensión Arterial Secundaria ¿por dónde empezar? / Secondary Arterial Hypertension, where to start?

30 to 40% of the adult population worldwide has been diagnosed with hypertension, among these patients 5 to 10% of them could have a possibly curable condition. In order to recognize this special population, the clinician must perform a complete work up and be aware of the main underlying causes of secondary hypertension. Often this could be a goal difficult to accomplish. The purpose of this article is to discuss the most frequent causes of secondary hypertension and offer a diagnostic approach for these patients. Clinicians should never forget that drug-related hypertension is a common cause that is discovered only with the help of a good medical history.

Síndrome de apneas e hipopneas obstructivas del sueño posicional / Positional Obstructive Sleep Apnea/Hypopnea Syndrome

La posición del cuerpo influye en la frecuencia y duración de apneas e hipopneas en los individuos con apneas obstructivas del sueño. La posición en decúbito supino es en la que más frecuentemente se registran eventos obstructivos y por lo tanto mayores valores en los indicadores de severidad. Aunque existen diferentes definiciones y clasificaciones, el síndrome de apneas del sueño posicional representa el 60% de todos los pacientes evaluados en una unidad de sueño, y su diferenciación tiene por objetivo determinar cuáles serán los candidatos que se beneficiarían de terapia posicional. Hasta el momento no hay una definición aceptada universalmente y la evidencia del beneficio clínico del rol de clasificar a los pacientes con apneas posicionales es aún controvertida en numerosos aspectos. La terapia posicional se basa en disminuir el tiempo en supino y la severidad de los eventos obstructivos, herramienta de la que se beneficiaría una importante proporción de los pacientes. La CPAP es el tratamiento más eficaz y se recomienda en formas severas y moderadas con manifestaciones clínicas y antecedentes cardiovasculares. En este grupo la terapia posicional podría recomendarse como tratamiento coadyuvante.

Body position during sleep time influences the frequency and duration of apneas and hypopneas in individuals who suffer from obstructive sleep apnea. Individuals in supine position show higher frequency of obstructive events and therefore, higher values in severity indexes. Though there are different definitions and classifications, the positional sleep apnea syndrome represents 60% of all patients evaluated in a sleep unit, and differentiating it aims to determine which candidates will benefit from positional therapy. There is no universally accepted definition and the evidence of the clinical benefit of classifying patients with positional sleep apnea is still controversial in many aspects. Positional therapy has the purpose of decreasing supine time and the severity of obstructive events. A significant proportion of patients would benefit from this treatment. The continuous positive airway pressure (CPAP) is the most effective treatment and is recommended for severe and moderate forms with clinical manifestations and cardiovascular history. In this group, positional therapy could be recommended as adjuvant treatment.

Selección de máscaras para el tratamiento con CPAP en el síndrome de apneas obstructivas del sueño / Mask Selection for Treatment with CPAP in Obstructive Sleep Apnea Syndrome

La presión positiva continua en las vías aéreas (CPAP) es el tratamiento estándar más eficaz para el síndrome de apneas e hipopneas obstructivas del sueño (SAHOS). La falta de adherencia se debe con frecuencia a la incomodidad o el disconfort generados por efectos secundarios relacionados con las máscaras. La aceptación de la CPAP depende en gran medida de la selección de la interfaz adecuada y para ello se requiere de experiencia del personal, de la posibilidad de seleccionar el modelo que mejor se adapta a cada paciente, y de que las interfaces cumplan con requisitos mínimos para proporcionar confort y eficacia terapéutica. La evidencia actual sugiere que la máscara nasal es mejor tolerada, requiere menor presión para resolver la obstrucción y se asocia con una mejor calidad de sueño y adherencia al tratamiento. Por lo tanto, máscaras o almohadillas nasales deben ser la primera opción. Máscaras oronasales pueden ser apropiadas cuando no se tolere la máscara nasal o la fuga bucal documentada persista. Los especialistas en medicina respiratoria somos responsables de controlar el proceso de selección y suministro de la máscara y de orientar a nuestros pacientes acerca de las opciones disponibles.

Continuous positive airway pressure (CPAP) is the most effective standard treatment for the obstructive sleep apnea and hypopnea syndrome (OSAHS). The lack of adherence to the treatment is frequently due to inconvenience or discomfort generated by side effects related to the masks. CPAP acceptance depends greatly on the selection of the adequate interface. To make the right choice, it is necessary to have experienced personnel and the possibility to select the model that best suits every patient. Also, interfaces must meet minimum requirements to provide comfort and therapeutic efficacy. Current evidence suggests that the nasal mask is better tolerated, requires less pressure to solve obstructions and is associated with better quality of sleep and adherence to the treatment. So, nasal masks or pillows should be the first option. Oronasal masks may be suitable when the nasal mask is not tolerated or the documented oral leakage persists. Specialists in respiratory medicine are responsible for controlling the process of selection and administration of the mask and guiding our patients on the available options.

Clinical Characteristics of Patients with Very Severe Obstructive Sleep Apnea

Introduction: The presence of obstructive sleep apneas (OSA) is a prevalent disease, whose severity is determined from the Apnea- Hypopnea Index (AHI). Very severe OSA (vsOSA) is defined by an AHI ≥ 60 events/hour; with clinical characteristics that could be different. The purpose of this study was to describe the clinical characteristics of patients with sOSA and compare them with less severe manifestations of this disease. Materials and Methods: Retrospective study of patients referred to a specialized hypertension center who met clinical criteria for the study of OSA. Patients were analyzed by means of a respiratory polygraphy, Ambulatory Monitoring of Arterial Pressure (AMAP), questionnaires and laboratory tests. We used non-parametric tests for the analysis of the results. Results: Of the 115 patients with OSA included in the study, 57 showed moderate OSA (mOSA), 48 sOSA and 10 vsOSA. No statistically significant differences were observed in age, Body Mass Index (BMI), glycemia, percentage of diabetic patients, or waist or neck diameter. We observed that the proportion of patients with arterial hypertension became higher as the severity of the OSA increased. This increase was significant only regarding the value of diastolic arterial pressure in very severe patients (vsOSA: 94.0 ± 7.7 mmHg vs. sOSA: 87.9 ± 8.7 mmHg and mOSA: 84.4 ± 8.2 mmHg; p < 0.05 and p < 0.01, respectively). Conclusions: In agreement with previous studies, our patients with vsOSA showed a higher degree of diastolic hypertension with clinical characteristics similar to less severe manifestations of OSA.

Characterization of Hemodynamic Patterns in Patients with Arterial Hypertension and Obstructive Sleep Apneas: Pilot Study Using Impedance Cardiography

Introduction: Arterial hypertension and obstructive sleep apneas are high prevalence diseases frequently associated. Understanding the hemodynamic profiles would allow treatment administration basing on the changes produced by the combination of both diseases. Materials and Methods: A prospective, exploratory pilot study was conducted with the purpose of characterizing the hemodynamic patterns of patients referred to the Arterial Hypertension Center who were without pharmacological treatment at the time of consultation. The hemodynamic pattern and thoracic fluid content were evaluated by impedance cardiography. In addition, office and 24-hour ambulatory monitoring of arterial pressure values were recorded; and the suspicion of sleep apnea was objectively assessed by means of home respiratory polygraphy. Results: 58 patients were included. The diagnosis of sleep apnea was confirmed in 84.5% of the cases (46.5% moderate to severe), and arterial hypertension in 65.2%. The findings of this study showed a progressive decrease in the proportion of the normodynamic pattern and normal thoracic fluid content, in relation to the increase in the severity of the respiratory sleep disorder (p 0.5). Furthermore, office systolic and diastolic pressure showed a progressive increase in relation to the increase in the severity of sleep apnea (p 0.05 and 0.01). Conclusion: The moderate-severe respiratory sleep disorder was related to an increase in resting blood pressure and a trend that did not reach statistical significance in the findings of altered hemodynamic patterns.

STOP-BANG, una herramienta útil y sencilla para el cribado del síndrome de apneas hipopneas obstructivas del sueño / STOP-BANG, a useful and easy tool for the screening of obstructive sleep apnea

El cuestionario STOP-BANG, del acrónimo en inglés S snore (ronquido), T tired (cansancio), Oobserved apneas (apneas observadas), P pressure (hipertensión arterial), B BMI (índice de masa corporal >35 kg/m2), A age (edad > 50 años), N neck (circunferencia del cuello > 40 cm) y G gender (sexo masculino), es una herramienta sencilla que permite detectar pacientes con síndrome de apneas/ hipopneas obstructivas del sueño (SAHOS). Si el paciente suma 3 o más puntos se considera que tiene una alta probabilidad de padecerlo. El objetivo de nuestro trabajo fue evaluar la capacidad del cuestionario STOP-BANG y compararla con la habilidad del médico neumonólogo capacitado en sueño para determinar la probabilidad de tener SAHOS. Se analizaron en forma retrospectiva 327 pacientes con sospecha de esta condición. Sexo masculino 171 (52.3%), edad 49.8 (37.9-61.7) años, índice de masa corporal (IMC) 38.7 (32.5-46) kg/m², circunferencia del cuello 44 (41-47.5) cm, roncadores 311 (95.1%), con somnolencia o cansancio 232 (70.9%), con apneas observadas 206 (63%), HTA 169 (51.7%), polisomnografía (PSG) normal 42 (12.9%), leve 65 (19.9%), moderada 59 (18%) y grave 161 (49.2%). La sensibilidad y especificidad del STOP-BANG, tomando como punto de corte un índice de perturbación respiratoria (IPR) = 15, fueron 99.1% y 14.0%, área bajo la curva (ABC) 0.755 (0.704-0.800), las de la habilidad del médico fueron 89.1% y 58.9%, ABC 0.550 (0.542-0.638). El STOP-BANG es una herramienta de fácil aplicación para el cribado de pacientes con sospecha de SAHOS.

The STO-BANG questionnaire, S standing for snore, T tired, O observed apneas, P pressure (arterial hypertension), B BMI (body mass index > 35 kg/ m2), A age (> 50 years old), N neck circumference (> 40 cm), G gender (male); is a simple tool that enables the detection of patients with obstructive sleep apnea syndrome (OSA). If the patient adds 3 or more points, it is considered to have a high probability of having this disease. Our goal was to evaluate the capacity of the STOP-BANG questionnaire and to compare it with the ability of a sleep trained pulmonologist in determining the probability of OSA. A retrospective analysis of 327 patients suspected of having this condition was performed. One hundred and seventy-one were males (52.3%), 49.8 years old (37.9-61.7), BMI 38.7 kg/m² (32.5-46), neck circumference 44 cm (41-47.5), 311 snorers (95.1%), 232 with daytime sleepiness or usual tiredness (70.9%), 206 with observed apneas (63%), 169 with arterial hypertension (51.7%), normal polysomnography 42 (12.9%), mild 65 (19.9%), moderate 59 (18%), severe 161 (49.2%). The STOP-BANG´s sensibility and specificity, taking as a cut-off point a respiratory disturbance index (RDI) > or = to 15, was 99.1% and 14.0% respectively, area under curve (AUC) 0.755 (0.704-0.800), the values for the PR actioner's ability were 89.1% and 58.9% respectively, AUC 0.550 (0.542-0.638). The STOP-BANG questionnaire is easy to implement as a screening tool.

Sleep Related Breathing Disorders: What & Why A Dentist Should Know? An Overview Of Dental Sleep Medicine.

Abstract: This article overviews the signs, symptoms, diagnosis and other facets of SRBDs ( sleep related breathing disorders. Snoring and EDS (excessive day time sleepiness) are the commonest signs of OSAs (obstructive sleep apneas). OSA are known to impact cvs, respiratory & metabolic balance. A new paradigm has evolved inter-connecting SRBDs& chronic periodontitis. So as to help a dentist to diagnose & manage SRBDs in dental scenario.

La neurología en un personaje de Dickens: síndrome pickwickiano, apneas hipopneas del sueño e hipertensión intracraneal

En muchos casos, la literatura de ficción se ha adelantado a la ciencia. Charles Dickens (1812-1870) pobló su obra con un tropel de notables personajes. Como la mayoría de los grandes novelistas, le adornaban finos dotes de observación y una extraordinaria capacidad descriptiva. Uno de sus protagonistas secundarios se ganó un puesto en los anales de la medicina. El logro de esta empresa se da al presentarnos la figura de un sirviente gordo y somnoliento llamado Joe, que a pesar de tener un pequeño y breve rol en el capítulo 54 de sus “Pickwick Papers” (1836), ha trascendido al lenguaje médico diario. La cómica caricatura que caracteriza al individuo obeso, sobrevivió en el ámbito de la medicina como un caso clásico de apneas del sueño: el síndrome de Pickwick o más precisamente, el síndrome Pickwickiano. Debieron transcurrir más de 120 años para que Burwell y sus colaboradores, hallaran una explicación fisiopatológicaal fenotipo de Joe, ese “niño gordinflón, rosado y roncador con la respiración entrecortada, eternamente somnoliento”,describiendo así, la presencia del síndrome apneashipopneas del sueño e hipoventilación alveolar en el sujeto obeso. La presencia de hipertensión intracraneal es otro de sus infrecuentes componentes. Describimos una serie de cuatro pacientes

In many cases, fictional literature has preceded science. Charles Dickens (1812-1870) filled his novels with anumber of noteworthy characters. As most great novelists, he possessed fine observation skills and an extraordinary capacity for description. In fact, one of his secondary characters gained a place in the world of medicine. From the “Pickwick Papers” (1836), Joe, the overweight and lazy servant, in spite of his brief appearance in chapter 54, has transcended to become part of the physician’s every day lingo. The amusing depiction that characterizes the overweight individual, survived in the medical world as the classic case of sleep apneas, the Pickwick syndrome or more precisely, the Pickwickian syndrome. After 120 years Burwell and his collaborators found a physiopathological explanation to the phenotype of Joe, ¨that fat and red-faced, chubby, plump and wheeze boy, in a state of somnolence”, so describing the presence of sleep apneas hypopneas and alveolar hypoventilation in obese individuals. The presence of intracranial hypertension is another of its infrequent components. We described a series of 4 of such cases.

Utilidad diagnóstica de un cuestionario de sueño y de la escala de somnolencia de Epworth en el síndrome de apneas/hipopneas obstructivas del sueño (SAHOS) / The usefulness of a sleep questionnaire and the epworth sleep scale in the diagnosis of obstructive sleep apnea syndrome (OSAS)

Introduction: Obstructive sleep apnea syndrome (OSAS) is a common disease associated with significant morbidity, including excessive daytime sleepiness, cardiovascular disease and stroke. Method: We studied prospectively the patients sent to our sleep laboratory for polysomnography (PSG) during 6 months. One-hundred patients were interviewed with a sleep questionnaire, 3 of them were ruled out because the lacking of PSG and 2 who no completed the Epworth sleep scale (ESS). Results: Out of the 95 patients, there were 85 men and 10 women, with a mean age of 47.4 +/- 12.5 years, obesity was found in 42.5 percent, an ESS greater than 11 points was found in 56.8 percent, loud snoring in 93.7 percent, breathing cessation in 68.4 percent, excessive daytime somnolence in 57.9 percent. PSG revealed no OSAS in 14.7 percent, slight OSAS in 27.4 percent, moderate OSAS in 21 percent y severe OSAS in 36.8 percent. Body mass index and breathing cessation reported by the couple had the highest discriminative power with a sensibility of 87 percent and specificity of 50 percent for ruled out severe OSAS. Conclusion: A severe OSAS is less probable when there is absence of breathing cessation during sleep reported by the couple and an IMC <30 Kg/m².

Introducción: El SAHOS presenta una alta prevalencia en estudios internacionales, con importantes repercusiones en los sistemas cardio, cerebrovascular y en la calidad de vida de las personas. Método: Estudiamos prospectivamente a los pacientes enviados para Polisomnografia (PSG) a nuestro laboratorio de sueño, en un período de 6 meses. Previo consentimiento informado, se les aplicó la Escala de Somnolencia de Epworth (EE) y un Cuestionario de Sueño. Fueron entrevistados 100 pacientes, excluyéndose 3 por no haberse realizado PSG y 2 que no completaron la EE. Resultados: Se analizaron 95 pacientes, 89,5 por ciento hombres, edad promedio 47,4 +/- 12,5 años, obesidad en 49,5 por ciento, EE mayor de 11 en 56,8 por ciento, ronquido en 93,7 por ciento, pausas respiratorias en 68,4 por ciento, somnolencia diurna excesiva en 57,9 por ciento, cansancio al despertar en 86,3 por ciento. La PSG no demostró SAHOS en 14,7 por ciento, hubo 27,4 por ciento con SAHOS leve, 21 por ciento> moderado y 36,8 por ciento> severo. Las variables presencia de pausas respiratorias observadas por la pareja e índice de masa corporal (IMC) predicen la ausencia de SAHOS severo, con una sensibilidad de 87 por ciento y especificidad de 50 por ciento. Conclusión: En la evaluación de pacientes con sospecha de SAHOS, la no observación de pausas respiratorias durante el sueño por parte de la pareja y el IMC menor de 30 Kg/m² hacen menos probable que exista un SAHOS severo.