Ventilation Obesity-Hypoventilation Syndrome


Article Author:
Marsha Antoine
Nakul Katyal


Article Editor:
Pradeep Bollu


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
6/25/2019 8:55:21 AM

Introduction

Obesity is associated with multiple medical complications. The prevalence of obesity in the United States has doubled since 1980. Currently, 35% of the United States population suffers from obesity. Given its extensive magnitude, it is paramount to address the associated metabolic, cardiovascular, and respiratory complications. [1][2][3]Obesity hypoventilation syndrome is one of the major respiratory consequences associated with obesity. The American Academy of Sleep Medicine introduced criteria for the diagnosis of OHS which includes:

  • Presence of hypoventilation during wakefulness (PaCO2 greater than 45 mm Hg) as measured by arterial PCO2, end-tidal PCO2, or transcutaneous PCO2
  • Presence of obesity (body mass index or BMI greater than 30 kg/m2; greater than the 95th percentile for age and sex for children)
  • Hypoventilation is not primarily due to lung parenchymal or airway disease, pulmonary vascular pathology, chest wall disorder (other than mass loading from obesity), medication use, neurologic disorder, muscle weakness, or a known congenital or idiopathic central alveolar hypoventilation syndrome.[4]

Etiology

Obesity is the number one contributor to OHS. Patients with body mass index (BMI) greater than 35 have a reported incidence of over 30%.[5][6][7]

Epidemiology

The prevalence of OHS in the adult population with BMI >40 kg/m2 ranges between 0.15% to 0.3%. Higher prevalence is seen in the population having obstructive sleep apnea (OSA). Many studies report a prevalence of OHS between 10% to 20% in patients with obesity with OSA. Among hospitalized adults with BMI greater than 35, the reported incidence is around 31%. For unknown reasons, a higher incidence rate is seen in men. Incidence is higher in African American population. OHS is known to occur at a lower BMI range in the Asian community.[8]

Pathophysiology

Obesity hypoventilation syndrome occurs as a result of complex interactions between multiple pathological processes including diminished respiratory drive, structural and functional respiratory impairment and sleep-related breathing alterations. Chronic steady state hypercapnia establishes as a result of the failure of compensatory ventilatory mechanisms.[5][9][10][11]

Excessive Load on Respiratory System

Respiratory Muscle Weakness

OHS patients have a moderate reduction in their respiratory muscle strength, which typically worsens in the supine position. In morbid obesity, accumulation of fat around the abdominal wall and chest significantly reduces pulmonary volumes and chest wall distensibility. OHS patients have a characteristic pattern of breathing that results in an increase in the airway resistance and a decrease in the distensibility leading to an increased respiratory effort.

Alterations of Respiratory Mechanics

Due to reduced pulmonary distensibility, obese patients suffer reduced ventilation in the lower pulmonary lobes. The alveoli close before the end of the expiration thus producing a characteristic breathing pattern of low tidal volume and an increased respiratory rate, causing an increase in the dead ventilation space. Decreased ventilation of the lower lobes causes alterations in the ventilation-perfusion (V/Q), thus triggering hypoxemia. Total lung capacity (TLC), expiratory reserve volume (ERV) and residual functional capacity (RFC) are reduced in patients with OHS as opposed to eucapnic obese patients.

Blunted Respiratory Drive

Patients with OHS have a blunted respiratory drive in response to a hypercapnic challenge. Multiple possible pathogenic mechanisms have been proposed to explain the blunted respiratory response including possible leptin resistance, genetic predisposition, and sleep-disordered breathing.

Leptin is produced in the adipose tissue. It regulates appetite and stimulates ventilation. Genetically-altered, obese mice with a leptin deficit are phenotypically similar to patients with OHS. These mice develop obesity, suffer from chronic hypercapnia while awake, in spite of increased ventilation which is in response to the increased metabolic production of CO2, and have decreased ventilatory response capacity. Importantly, replacement of leptin reverses chronic hypercapnia thus indicating a possible role in the pathogenesis of OHS.

Intrinsically diminished chemosensitivity to CO2 retention has been reported in OHS patients. It is possible that this familial diminished hypoxic and hypercapnic chemosensitivity could be the underlying reason for hypoventilation in patients with idiopathic obesity hypoventilation syndrome.

Sleep-Disordered Breathing

Obstructive sleep apnea is seen in about 90% of the patients with OHS. The PaCO2 increases are secondary to the cessation of ventilation during apneic events and continued metabolic production of CO2. Eucapnic patients can normalize the PaCO2 levels via compensatory augmentation of alveolar ventilation which increases CO2 clearance. However, in OHS patients, the compensatory mechanism is disrupted causing retention of CO2. In response to transitory hypercapnia, the renal system decreases bicarbonate clearance to compensate the hypercapnic pH drop. Plasma bicarbonate increases thus causing a gradual bicarbonate build-up. This built up eventually blunts the ventilatory response to carbon dioxide, thus fostering the development of nocturnal hypoventilation.

Sleep Hypoventilation

Almost 5% to 10 % of patients with OHS have sleep hypoventilation and a PaCO2 elevation during sleep of 10 mm Hg or higher. These patients are clinically indistinguishable from those with concomitant OSA. Sustained hypoxia significantly delays the warning signals of decreased ventilation and could potentially contribute to hypoventilation.

History and Physical

While some patients with OHS present with acute on chronic exacerbation of respiratory failure with acute respiratory acidosis, other patients remain clinically stable at the time of diagnosis. Majority patients have classic symptoms including loud snoring, nocturnal choking episodes with witnessed apneas, excessive daytime sleepiness, and morning headaches. Patients often exhibit dyspnea and may have signs of cor pulmonale. Classical physical examination findings include an enlarged neck circumference, crowded oropharynx, a prominent pulmonic component of the second heart sound on cardiac auscultation, and lower extremity edema.

Evaluation

Clinical suspicion should be high in patients with BMI > 30 kg/m2 with unexplained dyspnea on exertion and hypersomnolence [3]. The diagnostic approach's aim is to demonstrate daytime hypoventilation. The most definitive diagnostic test for alveolar hypoventilation is an arterial blood gas analysis. Unfortunately, an ABG is not readily done in an outpatient setting. However, most patients with OHS most common initial presentation is in a hospital setting after presenting with an acute exacerbation where an ABG along with a basic metabolic panel can be done. Their initial laboratory values will show elevated serum bicarbonate level which is typically seen as a result of metabolic compensation of respiratory acidosis which points toward the chronic nature of hypercapnia. This is why a serum bicarbonate level can sometimes serve as a sensitive test to screen for chronic hypercapnia but ultimately an arterial blood gas should show evidence of hypoventilation in complete wakefulness. Polymnography is not required for diagnosis but helps distinguish between patients with coexistent OSA from those with actual sleep hypoventilation. Sleep hypoventilation is defined as a 10 mmHG increase in PaCO2 above that of wakefulness that is not secondary to obstructive apneas or hypopnea. The percent of total sleep time with SpO2 spent below 90% can be a useful polysomnographic variable for evaluation of OHS patients. OHS is a diagnosis of exclusion that requires to be distinguished from disorders that are also associated with hypoventilation. Pulmonary function testing can exclude other causes of hypercapnia such as COPD. In OHS, PFT typically shows a mild to moderate restrictive defect. The expiratory reserve volume is significantly reduced along with mild reductions in maximum expiratory and inspiratory pressures secondary to a combination of altered respiratory mechanics and weak respiratory muscles. Imagings may identify anatomical obstructions such as severe chest-wall disorders. A complete blood count should be obtained to rule out secondary erythrocytosis. Thyroid function tests are to be obtained as well to exclude severe hypothyroidism. 

Treatment / Management

OHS is associated with significantly high rate of morbidity and mortality. Although treatment modalities target different aspects of the underlying pathophysiology, the goal is normalization of arterial carbon dioxide, reduction of oxyhemoglobin desaturation and improvement in symptoms. Several therapeutic options have been tried including positive airway pressure therapy, weight reduction surgery and pharmacotherapy.[12][13]

Positive Airway Pressure Therapy

Noninvasive positive airway pressure therapy is typically the first-line treatment for OHS. Noninvasive airway pressure therapy significantly reduces the nocturnal built up of PaCO2 and improves sleepiness during the daytime. The available treatment options includes Continuous positive airway pressure (CPAP), bi-level PAP, and other noninvasive ventilation (NIV) modalities. Although there is no defined guidelines for using particular treatment therapy, the current recommendation is to use CPAP if concomitant sleep-related breathing disorders are present. NIMV can be beneficial in patients having hypercapnia in the absence of significant apnea or hypopnea. The German society of pneumology recommends the use of NIMV in the absence of OSA, in the presence of OSA with significant comorbidities and with a CO2 level above 55 mm Hg for over 5 minutes or saturation of under 80% for over 10 minutes. The Canadian thoracic society recommends CPAP use in patients with a minor degree of nocturnal desaturation and no nocturnal rise of PaCO2. Bi-level PAP is the treatment of choice in OHS patients with significant nocturnal desaturation or the nocturnal rise of PaCO2. A recent study compared the 3 standard treatments for OHS including NIV, CPAP, and lifestyle modification. This study showed that both NIV and CPAP significantly improved polysomnographic parameters, although NIV was superior in improving respiratory parameters as compared to other treatment modalities. In a total of 351 patients compared to baseline, at 2 months, the 3 treatments showed a reduction in PaCO2 of 5.5, 3.7, and 3.2 with NIV, CPAP, and lifestyle modification respectively.

Surgery

Tracheostomy 

Tracheostomy relieves the airway obstruction during sleep, thus improving the alveolar ventilation and waking PaCO2. However, some patients still may not return to eucapnic state post tracheostomy, as it does not affect CO2 production and impaired muscle strength.

Weight reduction 

Numerous studies have shown improvement in OHS symptoms with weight reduction. Weight loss significantly reduces CO2 production and improve sleep apnea severity and alveolar ventilation. It also improves pulmonary artery hypertension and left ventricular dysfunction which can greatly reduce the cardiovascular compromise in OHS patients. Ideally, lifestyle modification therapy should be tried initially for weight loss. Surgical options should be considered for refractory cases.Pharmacotherapy

Medroxyprogesterone and acetazolamide can potentially reverse the hypercapnia associated with OHS; however, routine use is not recommended given the narrow safety margin and long-term side effects.

Leptin replacement therapy has been shown to relieve nocturnal hypoventilation and airway obstruction during sleep secondary to increased respiratory drive to both upper airway and diaphragm in experimental mice studies, but human use is not recommended.

Differential Diagnosis

Limitation to Ventilation

  • Chest wall diseases
  • Neuromuscular diseases
  • Obstructive lung disease

Central Control Defects

  • Congenital Central Hypoventilation (Ondine’s curse)
  • PHOX2B mutation on chromosome 4p12
  • Brainstem lesions
  • Carotid body disease
  • Metabolic alkalosis

Combined Defects

  • Cronic obstructive pulmonary disease (COPD)
  • Hypothyroidism
  • Sleep apnea

Prognosis

Obesity hypoventilation is associated with reduced quality of life and prolonged admission rates and time in intensive care unit. In patients with other medical conditions, such as diabetes, asthma , the mortality rates are significantly high with 23% over 18 months and 46% over 50 months. Early use of CPAP can reduce the associated mortality by 10%. 

Pearls and Other Issues

  • Obesity is associated with multiple medical complications. Obesity hypoventilation syndrome is one of the major respiratory consequence associated with obesity.
  • Presence of hypoventilation during wakefulness with PaCO2 greater than 45 mm Hg in the presence of obesity (BMI greater than 30 kg/m2) confirms the diagnosis, given that hypoventilation is not due to lung parenchymal or airway disease, pulmonary vascular pathology or chest wall disorder.
  • Serum bicarbonate levels, therefore, can be used as a sensitive test to screen for chronic hypercapnia.
  • The percent of total sleep time with SpO2 spent below 90% can be a useful polysomnographic variable for evaluation of OHS patients
  • Noninvasive positive airway pressure therapy is the first line treatment for OHS which significantly reduces the nocturnal built up of PaCO2 and improves sleepiness during the daytime.

Enhancing Healthcare Team Outcomes

Obesity is best managed by a multidisciplinary team including dietitians, nurses, therapists, and pharmacists. Obesity has significant morbidity and mortality if it is left untreated. The key is to educate the patient on the harms of obesity. Patients need to be told to change their lifestyle, become physically active, maintain a healthy weight, and exercise regularly. All current therapies for obesity hypoventilation syndrome are palliative until the patient loses weight.

For patients who do not lose weight, the prognosis is poor with a shortened life expectancy.[14][15] (Level V)


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Ventilation Obesity-Hypoventilation Syndrome - Questions

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A 60-year-old female with a body mass index ( BMI) of 40 Kg/m2 presents to a primary care clinic to establish care. Her past medical history is insignificant. She complains of daytime fatigue, sleepiness and mild breathlessness on exertion. She denies any smoking history. The examination was limited due to her body habitus. She takes ibuprofen as needed for arthritic-type pain of her knees. Her vital signs were within normal limits. Her laboratory results are elevated serum bicarbonate level at 30. What is the most likely diagnosis?



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A 60-year-old male has been having sleep attacks for 6 months. He falls asleep several times a day, even during meetings. He was always obese but has gained 40 kg over the past 2 years. BMI was 35 kg/m2. What is the most likely diagnosis?



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A 72-year-old female with known diagnosis of obesity hypoventilation syndrome presented to the sleep clinic with complaint of progressively worsening nocturnal choking episodes, despite using continuous positive airway pressure (CPAP). The PaCO2 and pulse oximetry levels obtained in the clinic were 40 mmHg and 80% respectively. What should be the ideal therapeutic option for this patient at this time?



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A 51-year-old morbidly obese male presents to the clinic to be evaluated for daytime fatigue. He has a medical history of type 2 diabetes and hyperlipidemia. He takes metformin, atorvastatin, and aspirin. He complains that he has been feeling fatigued for months. He is unable to complete his routine task due to hypersomnolence. His vitals are normal during this visit. He has a BMI of 44. Which of the following tests is most appropriate in the evaluation of this patient?



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A 36-year-old female presents to the emergency department with complaints of productive cough, malaise, and fever. She has no known medical history and does not take any medications. Her blood pressure is 105/92 mmHg, temperature 101.3 F, respiratory rate 24/min, and heart rate 96/min. Her BMI is 40 kg/m2. This patient's pulse oximetry is 93% on room air. Examination shows jugular venous distention, clear lung fields. A portable chest x-ray shows low lung volumes but is unremarkable otherwise. Laboratory results show hemoglobin of 15 g/l, platelets 290000/microL, and leukocytes 5000/microL. His sodium is 142 mEq/L, potassium 4.3 mEq/L, chloride 99 mEq/L, bicarbonate 35 mEq/L, BUN 26 mg/dL, creatinine 1.0 mg/dL, and glucose 100 mg/dL. Which of the following is the best next step in managing this patient?



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Ventilation Obesity-Hypoventilation Syndrome - References

References

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