Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713


Publication continuous and bimonthly

SCImago Journal & Country Rank
Advanced Search


Current Issue: 2018 - Volume 44 - Number 6 (November/December)


Proportional weight loss in six months as a risk factor for mortality in stage IV nonsmall cell lung cancer

Perda de peso proporcional em seis meses como fator de risco para mortalidade no câncer de pulmão de células não pequenas estádio IV


Guilherme Watte1; 2; 5; a; Claudia Helena de Abreu Nunes1; b; Luzielio Alves Sidney-Filho3; c; Matheus Zanon2; 4; d; Stephan Philip Leonhardt Altmayer4; 5; e; Gabriel Sartori Pacini4; f; Marcelo Barros5; g; Ana Luiza Schneider Moreira4; h; Rafael José Vargas Alves1; i; Alice de Medeiros Zelmanowicz4; j; Bashir Mnene Matata2; k; Jose da Silva Moreira1; l


1. Programa de Pós-Graduação em Ciências Pneumológicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS - Porto Alegre (RS) Brasil.
2. Department of Clinical Research and Radiology, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom.
3. Faculdade de Medicina, Universidade Federal do Espírito Santo, Vitória (ES) Brasil.
4. Departamento de Medicina Clínica e Saúde Pública, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS) Brasil.
5. Programa de Pós-Graduação em Medicina e Ciências da Saúde, Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre (RS) Brasil.
a. b. c. d. e. f. g. h. i. j. k. l.



Objective: To evaluate different weight loss (WL) cut-off points as prognostic markers of 3-month survival after diagnosis of stage IV non-small cell lung cancer (NSCLC). Methods: This was a prospective study involving 104 patients with metastatic (stage IV) NSCLC who were admitted to a cancer treatment center in southern Brazil between January of 2014 and November of 2016. We evaluated total WL and WL per month, as well as WL and WL per month in the 6 months preceding the diagnosis. The patients were followed for 3 months after diagnosis. A Cox proportional hazards regression model and Kaplan-Meier curves were used in order to evaluate 3-month survival. Results: The median WL in the 6 months preceding the diagnosis was 6% (interquartile range, 0.0- 12.9%). Patients with WL ≥ 5% had a median survival of 78 days, compared with 85 days for those with WL < 5% (p = 0.047). Survival at 3 months was 72% for the patients with WL ≥ 5% (p = 0.047), 61% for those with WL ≥ 10% (p < 0.001), and 45% for those with WL ≥ 15% (p < 0.001). In the multivariate analysis, the hazard ratio for risk of death was 4.51 (95% CI: 1.32-15.39) for the patients with WL ≥ 5%, 6.34 (95% CI: 2.31-17.40) for those with WL ≥ 10%, and 14.17 (95% CI: 5.06-39.65) for those with WL ≥ 15%. Conclusions: WL in the 6 months preceding the diagnosis of NSCLC is a relevant prognostic factor and appears to be directly proportional to the rate of survival at 3 months.



Objetivo: Avaliar diferentes pontos de corte da perda de peso (PP) como marcadores prognósticos de sobrevida em 3 meses após o diagnóstico de câncer de pulmão de células não pequenas estádio IV (CPCNP). Métodos: Estudo prospectivo envolvendo 104 pacientes com CPCNP metastático (estádio IV) que foram internados em um centro de tratamento de câncer no sul do Brasil entre janeiro de 2014 e novembro de 2016. Avaliamos a PP total e PP por mês, bem como PP e PP por mês nos 6 meses anteriores ao diagnóstico. Os pacientes foram acompanhados por 3 meses após o diagnóstico. Um modelo de regressão de riscos proporcionais de Cox e curvas de Kaplan-Meier foram utilizados para avaliar a sobrevida em 3 meses. Resultados: A mediana da PP nos 6 meses anteriores ao diagnóstico foi de 6% (intervalo interquartil, 0,0-12,9%). Pacientes com PP ≥ 5% tiveram uma sobrevida mediana de 78 dias, comparados a 85 dias para aqueles com PP < 5% (p = 0,047). A sobrevida em 3 meses foi de 72% para os pacientes com PP ≥ 5% (p = 0,047), 61% para aqueles com PP ≥ 10% (p < 0,001) e 45% para aqueles com PP ≥ 15% (p < 0,001). Na análise multivariada, a taxa de risco para óbito foi de 4,51 (IC95%: 1,32-15,39) para os pacientes com PP ≥ 5%, 6,34 (IC95%: 2,31-17,40) para aqueles com PP ≥ 10%, e 14,17 (IC95%: 5,06-39,65) para aqueles com PP ≥ 15%. Conclusões: A PP nos 6 meses anteriores ao diagnóstico de CPCNP é um fator prognóstico relevante e parece ser diretamente proporcional à taxa de sobrevida em 3 meses.



Keywords: Weight loss; Carcinoma, non-small-cell lung; Prognosis.


Palavras-chave: Perda de peso; Carcinoma pulmonar de células não pequenas; Prognóstico.




Obesity hypoventilation syndrome (OHS) is defined as the presence of obesity and daytime hypoventilation (PaCO2 ≥ 45 mmHg) in patients without central, pulmonary, neuromuscular, metabolic, or chest wall disease that explains the hypercapnia.(1) Therefore, OHS is a diagnosis of exclusion, and other causes of hypercapnia should be investigated. Obesity is the hallmark of the disease, there being a correlation between body mass index (BMI) and disease prevalence.(1-5) The identification of OHS is important because of the possibility of clinical exacerbation leading to respiratory failure and the high mortality rate in untreated patients. OHS is accompanied by obstructive sleep apnea (OSA) in more than 90% of cases, and both share the same major risk factor, that is, obesity; however, the presence of OSA is not necessary for the diagnosis of OHS. This explains why polysomnography is not necessary for this diagnosis. Signs of right heart failure can be present in OHS and are secondary to chronic hypoxemia and pulmonary hypertension, both of which can accompany the clinical picture. In addition, arterial hypertension and insulin resistance are more prevalent in patients with OHS than in obese individuals without OHS.(1-3)

Since OHS is associated with high morbidity and mortality,(5-7) the objective of the present study was to conduct a current review of the epidemiology, pathophysiology, and treatment of OHS.


Obesity-related sleepiness was described in 1889, even prior to the recognition of OSA.(8) Bickelmann et al. published a case report in 1956(3) and popularized the term "Pickwickian syndrome" (an eponym that has fallen into disuse) in a reference to the character Fat Boy Joe from Charles Dickens's "The Posthumous Papers of the Pickwick Club," who was always sleepy and hungry and would often fall asleep on the job any time during the day.(9) The patient reported by Bickelmann et al.(3) had daytime hypoventilation, chronic hypoxemia, polycythemia, and pulmonary hypertension, with evidence of cor pulmonale. Several studies have since characterized the epidemiology, clinical picture, and pathophysiology of OHS.(1,2,4,7) Since 1999, the American Academy of Sleep Medicine has defined the diagnostic criteria for OHS.(10,11)


The prevalence of OHS is unknown because of the lack of population-based studies. The prevalence of OHS is estimated to be 10-20% in patients with OSA(7,12-16) and is estimated to be even higher in extremely obese patients.(7,14) Mokhlesi et al.(7) evaluated a population in the USA referred to a sleep medicine center for suspicion of OSA-180 patients were retrospectively selected, and 410 patients were prospectively selected. Of the patients diagnosed with OSA in the retrospective and prospective samples, 30% and 20%, respectively, met the criteria for OHS, and those percentages increased with increasing BMI. Laaban et al.(14) retrospectively evaluated patients receiving home treatment for OSA in France. The sample included 1,114 adults, of whom approximately 10% met the diagnostic criteria for OHS, and a positive association was also found with increasing BMI.(14) Akashiba et al.(12) evaluated 611 patients in Japan referred to sleep medicine centers for OSA and diagnosed OHS in 9% of the patients. The patients with OHS were younger, were more obese, and had more severe OSA when compared with those without OHS. In a different approach, Kessler et al.(17) evaluated patients with OHS and detected OSA in most of the patients (90%); in addition, OHS patients with OSA were found to have poorer gas exchange and poorer pulmonary hemodynamics than did those without OSA.

Seeking to determine the prevalence and, consequently, the degree of underdiagnosis of OHS, Nowbar et al.(5) conducted a study involving obese patients admitted to internal medicine services for any cause. Of 29 obese inpatients with a BMI > 50 kg/m2, 14 (48%) were diagnosed with OHS. In the same study, 31% of 150 obese inpatients did not have a previous diagnosis of OHS, although they met the criteria for this diagnosis.(5)

Because of the lack of studies on the prevalence of OHS in the general population, an exercise on epidemiological correlations has been repeatedly cited. Mokhlesi(18) infers that if approximately 3% of the general population in the USA are severely obese (BMI > 40 kg/m2), half of those individuals would have OSA. Considering, therefore, the estimate that 10-20% of severely obese patients with OSA would have OHS, a conservative estimate indicates a prevalence of OHS of 0.15-0.30% in the general population in the USA (ranging approximately from 1:300 to 1:600 adults).(18)


Patients with OHS use more health care resources in the period prior to the diagnosis than do obese individuals without OHS or the general population.(19) Obesity per se leads to a greater likelihood of diseases such as systemic arterial hypertension, diabetes, dyslipidemia, and hypothyroidism. Comorbidities such as heart failure, coronary artery disease, and cor pulmonale are more common in patients with OHS, and the likelihood that such patients will require invasive mechanical ventilation or ICU admission is also increased.(5,20) In addition, pulmonary hypertension is more common (50% vs. 15%) and more severe in patients with OHS than in patients with OSA.(16,21,22)

Berg et al.(19) conducted a study involving 20 patients with OHS, who were matched to control subjects by age, gender, and zip code (to try to equate socioeconomic factors). A comparison with controls revealed that the most common morbidities in patients with OHS were cardiovascular diseases: congestive heart failure (OR = 9.0; 95% CI: 2.3-35.0); angina pectoris (OR = 9.0; 95% CI: 1.4-57.1); and cor pulmonale (OR = 9.0; 95% CI: 1.4-57.1). In a retrospective study conducted by Basoglu & Tasbakan, having a BMI > 40 kg/m2 and obesity-related complications showed a strong association with an increased risk of premature death in hospitalized patients.(2) Nowbar et al.(5) reported that, at 18 months following hospital discharge, mortality was 23% in patients with obesity-related hypoventilation, which was almost twice as high as that among obese patients without hypoventilation.


OHS occurs within a triad: obesity; daytime gas exchange abnormalities (hypercapnia); and the absence of other causes for the findings (Chart 1).(23) The American Academy of Sleep Medicine defines OHS as follows: the presence of awake daytime alveolar hypoventilation (PaCO2 > 45 mmHg as measured at sea level) in patients with a BMI ≥ 30 kg/m2 in the absence of other causes of hypoventilation.(11)

The vast majority of patients with OHS have symptoms of OSA, including snoring, nighttime choking, witnessed apneas, nonrestorative sleep, excessive daytime sleepiness, and fatigue. In contrast to patients with OSA alone, patients with OHS complain of dyspnea, are often hypoxemic, and can have signs of cor pulmonale. Plethoric obese patients with hypoxemia, an increased neck circumference, a decreased airway area, a prominent P2 (a loud second heart sound) on cardiac auscultation, and leg edema, as determined by physical examination, are at risk of having OHS.(1)

OHS is a diagnosis of exclusion. Other causes of hypoventilation, such as COPD; severe interstitial lung disease; mechanical respiratory limitation (for example, chest wall disorders such as kyphoscoliosis); myopathies (such as myasthenia gravis); neurological diseases; central causes (such as cerebrovascular disease and untreated hypothyroidism); and congenital causes (such as Ondine's syndrome; Chart 1), should be ruled out.

Patients suspected of having OHS can initially be screened by pulse oximetry and by determination of serum levels of venous bicarbonate. Borderline oximetry values are common findings. Patients with OHS undergoing arterial blood gas analysis rarely have PaO2 values > 70 mmHg. Consequently, SpO2 values < 93% on pulse oximetry would be suggestive of hypoventilation. However, higher values are not exclusionary, which explains why this is not a necessary criterion to establish the diagnosis, although it helps in screening. Nocturnal oximetry showing sustained hypoxemia and no associated apneas strengthens the suspicion for hypoventilation. A serum bicarbonate level ≥ 27 mEq/L had a sensitivity of 92% and a specificity of 50%, justifying its use in screening.(7,24,25) After such screening, arterial blood gas analysis is mandatory. For excluding other causes of hypoventilation (Chart 1), pulmonary function testing and assessment of respiratory muscle strength (MIP and MEP), chest X-ray, electrocardiography, and thyroid function testing should be performed. In addition, the use of drugs and medications, such as sedatives, hypnotics, opiates, and alcohol (alcohol abuse), should be investigated. Polysomnography is not necessary for the diagnosis of OHS.(11) However, since it has been observed that individuals with OHS have obstructive events, as well as lower saturation in REM sleep (Figure 1), polysomnography is requested with a view to treating comorbid sleep apnea and to justifying possible treatments.(6)

Unfortunately, despite being simple in concept, the diagnosis of OHS is delayed in most cases, occurring during acute events of respiratory failure or cardiac decompensation.(5,26)


Several mechanisms are related to the pathogenesis of OHS (Figure 2), including an abnormal organic response of the respiratory system in certain obese individuals, as well as an inappropriate central response to hypercapnia and hypoxemia, in addition to neurohumoral changes. In comparison with other obese individuals, patients with OHS have decreased lung compliance, important reductions in functional residual capacity and chest wall compliance, and increased pulmonary resistance.(23,27)

Changes in pulmonary function

Obesity and the resulting greater chest wall thickness cause an excessive increase in the work of breathing. Breathing smaller volumes affects respiratory mechanics, reducing respiratory system compliance and increasing its resistance (which, in individuals with OHS, is approximately 20% higher than in other obese individuals and 60% higher than in normal-weight individuals).(23,27) Gas exchange is also affected, worsening the ventilation/perfusion ratio. Individuals with OHS tend to have lower tidal volume and higher RR, which increases the dead space effect. Consequently, hypoxemia is a common finding, which leads to an equally common outcome of pulmonary hypertension secondary to hypoxia.(16,17) In addition, abdominal fat deposition compromises the diaphragm's influence on ventilation, compromising muscle function. Furthermore, there is thinning of the diaphragm and increased oxidative stress.(28)

Ventilatory control

Patients with OHS have arterial CO2 retention. A reduction in CO2 chemosensitivity was initially believed to be the possible cause of this finding, which was proven untrue.(29-31) Unlike what occurs in chronic hypoxia, low daytime and nighttime saturation can be the cause of decreased ventilatory response.(32) Chemosensitivity is progressively impaired by increased CO2 levels. Chronic hypercapnia is also believed to result from the inability to eliminate CO2, which accumulates at night during apnea and hypopnea episodes, during the day (Figure 3).(30) A secondary mechanism that also impairs chemosensitivity is elevated serum and cerebrospinal fluid levels of bicarbonate.

Role of leptin

Leptin is a cytokine produced by adipocytes and may explain a causal relationship among obesity, ventilatory control, and chronic hypercapnia. Most data come from studies of mice. When obese, these animals, like humans, develop daytime hypercapnia and reduced ventilatory response to CO2. In mice, there is deficiency of leptin. Leptin replacement reverses hypoventilation in mice with leptin deficiency.(33)

Unlike in the animal model, there is no deficiency but rather an increase in leptin levels in obese humans. Leptin is believed to initially have a protective effect, stimulating the ventilatory response. The persistence of obesity would lead to leptin resistance (which is conceptually similar to insulin resistance), and thus, a consequent decrease in the ventilatory response to CO2.(25,32,34)


Weight loss

Significant weight loss promotes improvement in ventilatory parameters.(3,32) Bariatric surgery is the intervention resulting in the best outcome.(35) However, low-calorie diets may have satisfactory results. Bariatric surgery is the treatment of choice in the management of morbidly obese patients, but not every patient is a candidate for the procedure, given that the number of comorbidities that increase surgical risk is high. In fact, in some cases, the procedure will be contraindicated because of such comorbidities.

Although treatment improves ventilatory variables, it does not always resolve the problem. In a study conducted by Dixon et al.(36) involving 60 obese patients with a diagnosis of OSA who were divided into two groups-those undergoing calorie restriction and those undergoing bariatric surgery-weight loss was greater in the bariatric surgery group, but there was no statistically significant difference regarding the apnea-hypopnea index. Greenburg et al.(37) published a meta-analysis that included 12 studies involving 342 patients who underwent polysomnography before bariatric surgery and after maximal weight loss. There was a 71% reduction in the apnea-hypopnea index, from 55 events/h (95% IC: 49-60 events/h) to 16 events/h (95% CI: 13-19 events/h). It is known that 7% to 20% of such patients are unable to maintain a BMI loss of at least 20% after 5-10 years,(38,39) which requires continued surveillance even after the procedure. Only one study evaluated the impact of bariatric surgery in patients with OHS. Sugerman et al.(40) evaluated 61 patients with OHS undergoing bariatric surgery. In 31 patients, there was improvement in PaO2 (from 53 mmHg to 73 mmHg) and in PaCO2 (from 53 mmHg to 44 mmHg) at 1 year. At 5 years, only 12 patients underwent arterial blood gas analysis, which revealed marked worsening (mean PaO2 = 68 mmHg and mean PaCO2 = 47 mmHg); in addition, the mean BMI was found to have increased (from 38 kg/m2 to 40 kg/m2), having been high since the first postoperative year.

Oxygen therapy alone

Oxygen therapy alone is not appropriate, even in acute events, because it increases nocturnal CO2 retention (Haldane effect or "dead space" ventilation effect), which worsens sleep quality, and is considered a common error in the management of patients with OHS (this subject will be discussed below).(41)


There are no studies that examine the indications for phlebotomy in patients with OHS. Our group uses the indications for phlebotomy for heart disease patients and lung disease patients (hematocrit > 56% or symptoms of hyperviscosity).(42)


Tracheostomy was the first treatment instituted for OHS; however, today, tracheostomy is reserved only for patients who are refractory to noninvasive ventilation (NIV), because of risk and complications inherent in the procedure and in obese patients.(34)


Several medications (such as medroxyprogesterone and acetazolamide) have been tried to increase ventilatory response, without success, and are not recommended for the treatment of OHS.(25,32,34,43)

Positive pressure
Continuous positive airway pressure (CPAP) is the treatment of choice for stable OHS. CPAP improves alveolar ventilation by decreasing upper airway resistance, relieving the respiratory muscle load, and/or increasing central respiratory activity.(6,19,24,41,44-52) Patients with OHS should be initially treated with CPAP if they are clinically stable and if PaCO2 is not severely altered (< 55 mmHg). If either of these conditions is not met, NIV should be used. In OHS patients without OSA, NIV should also be used. CPAP therapy is typically administered via a nasal mask. Some studies have shown that oronasal masks are less efficient and are associated with poorer adherence and greater side effects than are nasal masks in patients with OSA. (53) Therefore, for long-term use, nasal masks are recommended. In critically ill patients with respiratory failure, oronasal masks are preferred.

In a randomized multicenter study involving 221 patients conducted in Spain, NIV, CPAP, and lifestyle change were compared. NIV and CPAP were more effective than lifestyle change in improving clinical symptoms and polysomnographic parameters. However, there were no significant differences between NIV and CPAP, although NIV resulted in slightly improved pulmonary function values.(54) Howard et al.(55) conducted a double-blind, randomized trial of CPAP versus NIV in 57 patients with OHS admitted to either the emergency room or an outpatient clinic. There were no differences in treatment failure between CPAP and NIV, and there were similarities in ventilatory parameters, quality of life, and cardiovascular risk markers at 3 months, regardless of OHS severity. Although there was a trend toward early improvement in the group treated with NIV, use of CPAP was safe even in patients who were more severely ill, provided that it occurred in the emergency room after stabilization with NIV and that patients were monitored for treatment failure (PaCO2 > 60 mmHg at 3 months of treatment or a 10-mmHg increase in PaCO2 at any given time point).(55) However, further long-term comparative studies are needed to compare NIV versus CPAP in terms of variables such as length of hospital stay, cardiovascular events, and mortality. In patients with refractory hypoventilation (PaCO2 > 45 mmHg despite proven adherence to treatment and use of PAP determined by titration and despite the elimination of obstructive events) or with persistent desaturation (SpO2 < 90% despite proven adherence to treatment and use of PAP determined by titration and despite the elimination of obstructive events), NIV should be used.(43,46,47,49,52,56,57)

Treatment objectives

The objective of therapy in OHS is to reverse the major abnormalities that give rise to the disease, that is, to normalize ventilation during sleep and to reduce body weight. The therapeutic goals for patients with OHS include normalization of PaCO2 during wakefulness and sleep; prevention of desaturations during sleep and wakefulness; control of erythrocytosis, pulmonary hypertension, and cor pulmonale; and relief of hypersomnia. Poor adherence to PAP is associated with incomplete clinical improvement. Adherence can be assessed by reviewing the memory card of NIV and CPAP devices.

Management in the emergency room: common errors in caring for patients with OHS
Overuse of supplemental oxygen

Hypercapnia can be aggravated by hyperoxia via several mechanisms: an increase in FiO2 can result in a decrease in minute volume and, consequently, a decrease in tidal volume due to the activity of peripheral chemoreceptors; oxygenation of hypoxic areas causes vasodilation that changes blood flow to previously poorly ventilated areas, causing an increase in dead space; and the Haldane effect causes a reduction in hemoglobin affinity for CO2 and decreases correction of hypoxia, causing increased release of CO2 in plasma, which increases hypercapnia.(29,41,58) Therefore, oxygen therapy alone is best indicated in hemodynamically stable patients with no excessive work of breathing (RR ≤ 30 breaths/min without use of accessory muscles or with other signs of risk of ventilatory failure), under clinical surveillance, with an SpO2 target of 89-92%.(41)

Overuse of loop diuretics

Patients with OHS are commonly affected by conditions that cause edema due to cor pulmonale. Since decompensation of cor pulmonale can be the cause for seeking medical care, a loop diuretic (furosemide) usually is used for the initial treatment of these patients in order to achieve a euvolemic state. However, overuse of diuretics can lead to acute prerenal renal failure. Contraction alkalosis secondary to the use of diuretics can worsen CO2 retention. In addition, overuse of furosemide can cause hypokalemia. Cautious use of diuretics is indicated in OHS, at the lowest dose possible to achieve a favorable clinical response and minimize the electrolytic and acid-metabolic impact. (41) The use of spironolactone for the prevention of hypokalemia is plausible.

Overuse of psychotropic drugs

The use of sedative/hypnotic drugs not only increases airway collapsibility but also decreases ventilatory response, which is harmful to patients with OHS.

Diagnostic confusion with COPD

Patients with chronic CO2 retention, such as patients with OHS, are commonly diagnosed with COPD, despite the absence of documented obstructive ventilatory disorders. A retrospective study by Marik & Desai(59) showed that, of the morbidly obese patients admitted to the ICU for respiratory failure secondary to OHS, 75% had been erroneously treated for COPD and 86% had been treated for congestive heart failure (Chart 2).


Patients with OHS commonly have a consultation with a pulmonologist in the preoperative period. In addition to comorbidity care and the required cardiovascular evaluation in obese patients or in those who are known to have or are highly suspected of having OSA, specific perioperative care is required for these patients whatever the procedure. In addition to the already suggested screening with pulse oximetry and determination of serum bicarbonate, other measures are required. If screening is positive and OHS is confirmed by arterial blood gas analysis, treatment should be started immediately, even a few days or weeks after the procedure; there is significant evidence of improved gas exchange and improved ventilatory control, either with one-level positive pressure or with two-level positive pressure.(60)

Obesity is a risk factor for difficult mask ventilation.(61) A retrospective study by Rose & Cohen, involving 18,500 patients, showed that obesity is also an independent risk factor for difficult intubation.(62) ≥Kheterpal et al.(63) evaluated 22,660 procedures and identified five risk factors (limited mandibular protrusion, increased neck circumference, OSA, snoring alone, and BMI ≥ 30 kg/m2) as independent predictors of difficult mask ventilation and difficult intubation during anesthesia induction. This suggests that patients with OHS are among those at highest risk for airway complications. (64) During anesthesia induction, patients with OHS should be placed in the ramp position with elevation of the torso and head (preferably at a 25° tilt). This has been shown to improve ventilation and the glottic view,(65) as well as oxygenation.(66)

Patients with OHS are more sensitive to the respiratory depressant effects of anesthetic agents and opioids because they are prone to airway collapse and inappropriate physiological response to hypercapnia and hypoxemia. Regional block should be chosen, when possible. In addition, during the procedure if possible, patients with OHS should be monitored with a capnograph. At the end of the procedure, it is recommended that patients be placed in the ramp position or in the lateral decubitus position for improved oxygenation and maintenance of the airways, and tracheal extubation should be performed only after the patient is fully conscious.(64)

With regard to postoperative care, the use of CPAP for 24-48 h after extubation can reduce the risk of postoperative complications and extubation failure in severely obese patients admitted to the ICU (an absolute risk reduction of 16%), with a reduction in mortality in patients with hypercapnia.(67,68) In addition, pain control has an impact on ventilatory status. Therefore, optimal analgesia is also required.
Figure 4 outlines a suggested algorithm for the screening and perioperative management of patients with suspected or confirmed OHS.


OHS is still a poorly recognized entity in Brazil. Delayed diagnosis of OHS is associated with an increase in morbidity, mortality, and costs of care of patients who are more severely ill. However, breaking free from myths and paradigms regarding diagnosis, such as that related to polysomnography, which is unnecessary, the possibility of screening for OHS with determination of venous bicarbonate, and the possibility of treatment with CPAP enable the diagnosis and treatment of OHS in a larger number of patients.

1. Mokhlesi B, Kryger MH, Grunstein RR. Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc. 2008;5(2):218-25.
2. Basoglu OK, Tasbakan MS. Comparison of clinical characteristics in patients with obesity hypoventilation syndrome and obese obstructive sleep apnea syndrome: a case-control study. Clin Respir J. 2014;8(2):167-74.
3. BICKELMANN AG, BURWELL CS, ROBIN ED, WHALEY RD. Extreme obesity associated with alveolar hypoventilation; a Pickwickian syndrome. Am J Med. 1956;21(5):811-8.
4. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med. 2005;118(9):948-56.
5. Nowbar S, Burkart KM, Gonzales R, Fedorowicz A, Gozansky WS, Gaudio JC, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004;116(1):1-7.
6. Castro-Añón O, Pérez de Llano LA, De la Fuente Sánchez S, Golpe R, Méndez Marote L, Castro-Castro J, et al. Obesity-hypoventilation syndrome: increased risk of death over sleep apnea syndrome. PLoS One. 2015;10(2):e0117808.
7. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007;11(2):117-24.
8. Lavie P. Who was the first to use the term Pickwickian in connection with sleepy patients? History of sleep apnoea syndrome. Sleep Med Rev. 2008;12(1):5-17.
9. Dickens C. The posthumous papers of the Pickwick Club. Boston: Riverside Press; 1867.
10. American Academy of Sleep Medicine. International Classification of Sleep Disorders. Darien, IL: the Academy; 1999.
11. American Academy of Sleep Medicine. Darien, IL: the Academy; 2014.
12. Akashiba T, Akahoshi T, Kawahara S, Uematsu A, Katsura K, Sakurai S, et al. Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study. Intern Med. 2006;45(20):1121-5.
13. Verin E, Tardif C, Pasquis P. Prevalence of daytime hypercapnia or hypoxia in patients with OSAS and normal lung function. Respir Med. 2001;95(8):693-6.
14. Laaban JP, Chailleux E. Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy. Chest. 2005;127(3):710-5.
15. Ayappa I, Berger KI, Norman RG, Oppenheimer BW, Rapoport DM, Goldring RM. Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2002;166(8):1112-5.
16. Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J. 1996;9(4):787-94.
17. Kessler R, Chaouat A, Schinkewitch P, Faller M, Casel S, Krieger J, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. 2001;120(2):369-76.
18. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care. 2010;55(10):1347-65; discussion 1363-5.
19. Berg G, Delaive K, Manfreda J, Walld R, Kryger MH. The use of health-care resources in obesity-hypoventilation syndrome. Chest. 2001;120(2):377-83.
20. Bender R, Trautner C, Spraul M, Berger M. Assessment of excess mortality in obesity. Am J Epidemiol. 1998;147(1):42-8.
21. Atwood CW Jr, McCrory D, Garcia JG, Abman SH, Ahearn GS; American College of Chest Physicians. Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1 Suppl):72S-77S.
22. Sugerman HJ, Baron PL, Fairman RP, Evans CR, Vetrovec GW. Hemodynamic dysfunction in obesity hypoventilation syndrome and the effects of treatment with surgically induced weight loss. Ann Surg. 1988;207(5):604-13.
23. Lopata M, Onal E. Mass loading, sleep apnea, and the pathogenesis of obesity hypoventilation. Am Rev Respir Dis. 1982;126(4):640-5.
24. Harada Y, Chihara Y, Azuma M, Murase K, Toyama Y, Yoshimura C, et al. Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels. Respirology. 2014;19(8):1233-40.
25. Piper AJ, Grunstein RR. Obesity hypoventilation syndrome: mechanisms and management. Am J Respir Crit Care Med. 2011;183(3):292-8.
26. Owens RL. A big problem in the ICU. Initiation of CPAP/bilevel PAP therapy. J Clin Sleep Med. 2014;10(10):1161-2.
27. Merkus PJ, van Pelt W, Quanjer PH. Effects of overweight on lung function. Arch Dis Child. 1991;66(2):273-4.
28. Becker HF, Piper AJ, Flynn WE, McNamara SG, Grunstein RR, Peter JH, et al. Breathing during sleep inpatients with nocturnal desaturation. Am J Respir Crit Care Med. 1999;159(1):112-8.
29. Hollier CA, Harmer AR, Maxwell LJ, Menadue C, Willson GN, Unger G, et al. Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. Thorax. 2014;69(4):346-53.
30. Rapoport M, Garay SM, Epstein H, Goldring RM. Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome". Chest. 1986;89(5):627-35.
31. Berger KI, Ayappa I, Sorkin IB, Norman RG, Rapoport DM, Goldring RM. CO(2) homeostasis during periodic breathing in obstructive sleep apnea. J Appl Physiol (1095). 2000;88(1):257-64.
32. Piper AJ. Obesity hypoventilation syndrome--the big and the breathless. Sleep Med Rev. 2011;15(2):79-89.
33. Tankersley CG, O'Donnell C, Daood MJ, Watchko JF, Mitzner W, Schwartz A, et al. Leptin attenuates respiratory complications associated with the obese phenotype. J Appl Physiol (1985). 1998;85(6):2261-9.
34. Selim BJ, Junna MR, Morgenthaler TI. Therapy for sleep hypoventilation and central apnea syndromes. Curr Treat Options Neurol. 2012;14(5):427-37.
35. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-52.
36. Dixon JB, Schachter LM, O'Brien PE, Jones K, Grima M, Lambert G, et al. Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;308(11):1142-9.
37. Greenburg DL, Lettieri CJ, Eliasson AH. Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis. Am J Med. 2009;122(6):535-42.
38. le Roux CW, Heneghan HM. Bariatric Surgery for Obesity. Med Clin N Am. 2018;(102):165-82.
39. Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;(351):2683-93.
40. Sugerman HJ, Fairman RP, Sood R, Engle K, Wolfe L, Kellum J. Long-term effects of gastric surgery for treating respiratory insufficiency of obesity. Am J Clin Nutr. 1992;55(2 Suppl):597S-601S.
41. Manthous CA, Mokhlesi B. Avoiding Management Errors in Patients with Obesity Hypoventilation Syndrome. Ann Am Thorac Soc. 2016;13(1):109-14.
42. McMullin MF, Bareford D, Campbell P, Green AR, Harrison C, Hunt B, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol. 2005;130(2):174-95.
43. Piper A. Obesity Hypoventilation Syndrome Weighing in on Therapy Options. Chest. 2016;149(3):856-68.
44. Borel JC, Pepin JL, Pison C, Vesin A, Gonzalez-Bermejo J, Court-Fortune I, et al. Long-term adherence with non-invasive ventilation improves prognosis in obese COPD patients. Respirology. 2014;19(6):857-65.
45. Bülbül Y, Ayik S, Ozlu T, Orem A. Frequency and predictors of obesity hypoventilation in hospitalized patients at a tertiary health care institution. Ann Thorac Med. 2014;9(2):87-91.
46. Combs D, Shetty S, Parthasarathy S. Advances in Positive Airway Pressure Treatment Modalities for Hypoventilation Syndromes. Sleep Med Clin. 2014;9(3):315-325.
47. Esquinas AM, Petroianni A. Non-invasive mechanical ventilation in obesity hypoventilation syndrome: are multimodal therapeutic strategies disease essential? Respirology. 2013;18(2):385.
48. Jaoude P, Kufel T, El-Solh AA. Survival benefit of CPAP favors hypercapnic patients with the overlap syndrome. Lung. 2014;192(2):251-8.
49. Lemyze M, Taufour P, Duhamel A, Temime J, Nigeon O, Vangrunderbeeck N, et al. Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure. PLoS One. 2014;9(5):e97563.
50. Palen BN, Kapur VK. Tailoring Therapy for Obesity Hypoventilation Syndrome. Am J Respir Crit Care Med. 2015;192(1):8-10.
51. Salord N, Mayos M, Miralda RM, Farré A, Carreras M, Sust R, et al. Continuous positive airway pressure in clinically stable patients with mild-to-moderate obesity hypoventilation syndrome and obstructive sleep apnoea. Respirology. 2013;18(7):1135-42.
52. Storre JH, Seuthe B, Fiechter R, Milioglou S, Dreher M, Sorichter S, et al. Average volume-assured pressure support in obesity hypoventilation: A randomized crossover trial. Chest. 2006;130(3):815-21.
53. Andrade RG, Piccin VS, Nascimento JA, Viana FM, Genta PR, Lorenzi-Filho G. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea. J Bras Pneumol. 2014;40(6):658-68.
54. Masa JF, Corral J, Alonso ML, Ordax E, Troncoso MF, Gonzalez M, et al. Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome: Pickwick Study. Am J Respir Crit Care Med. 2015;192(1):86-95.
55. Howard ME, Piper AJ, Stevens B, Holland AE, Yee BJ, Dabscheck E, et al. A randomised controlled trial of CPAP vs non-invasive ventilation for initial treatment of obesity hypoventilation syndrome. Thorax. 2017;72(5):437-444.
56. Ojeda Castillejo E, de Lucas Ramos P, López Martin S, Resano Barrios P, Rodriguez Rodríguez P, Morán Caicedo L, et al. Noninvasive mechanical ventilation in patients with obesity hypoventilation syndrome. long-term outcome and prognostic factors. Arch Bronconeumol. 2015;51(2):61-8.
57. Waldhorn RE. Nocturnal nasal intermittent positive pressure ventilation with bi-level positive airway pressure (BiPAP) in respiratory failure. Chest. 1992;101(2):516-21.
58. Masa JF, Corral J, Romero A, Caballero C, Terán-Santos J, Alonso-Álvarez ML, et al. The effect of supplemental oxygen in obesity hypoventilation syndrome. J Clin Sleep Med. 2016;12(10):1379-1388.
59. Marik PE, Desai H. Characteristics of patients with the "malignant obesity hypoventilation syndrome" admitted to an ICU. J Intensive Care Med. 2012;28(2):124-30.
60. Chouri-Pontarollo N, Borel J, Tamisier R, Wuyam B, Levy P, Pepin J. Impaired objective daytime vigilance in obesity-hypoventilation syndrome: Impact of noninvasive ventilation. Chest. 2007;131(1):148-55.
61. Langeron O, Masso E, Huraux C, Guggiari M, Bianchi A, Coriat P, et al. Prediction of difficult mask ventilation. Anesthesiology. 2000;92(5):1229-36.
62. Rose DK, Cohen MM. The airway: problems and predictions in 18,500 patients. Can J Anaesth. 1994;41(5 Pt 1):372-83.
63. Kheterpal S, Han R, Tremper KK, Shanks A, Tait AR, O'Reilly M, et al. Incidence and predictors of difficult and impossible mask ventilation. Anesthesiology. 2006;105(5):885-91.
64. Chau EH, Lam D, Wong J, Mokhlesi B, Chung F. Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology. 2012;117(1):188-205.
65. Cattano D, Melnikov V, Khalil Y, Sridhar S, Hagberg CA. An evaluation of the rapid airway management positioner in obese patients undergoing gastric bypass or laparoscopic gastric banding surgery. Obes Surg. 2010;20(10):1436-41.
66. Dixon B, Dixon J, Carden J, Burn A, Schachter L, Playfair J, et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 2005;102(6):1110-5; discussion 5A.
67. Rennotte MT, Baele P, Aubert G, Rodenstein DO. Nasal continuous positive airway pressure in the perioperative management of patients with obstructive sleep apnea submitted to surgery. Chest. 1995;107(2):367-74.
68. El-Solh AA, Aquilina A, Pineda L, Dhanvantri V, Grant B, Bouquin P. Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients. Eur Respir J. 2006;28(3):588-95.



The Brazilian Journal of Pulmonology is indexed in:

Latindex Lilacs SciELO PubMed ISI Scopus Copernicus pmc


CNPq, Capes, Ministério da Educação, Ministério da Ciência e Tecnologia, Governo Federal, Brasil, País Rico é País sem Pobreza
Secretariat of the Brazilian Journal of Pulmonology
SCS Quadra 01, Bloco K, Salas 203/204 Ed. Denasa. CEP: 70.398-900 - Brasília - DF
Fone/fax: 0800 61 6218/ (55) (61) 3245 1030/ (55) (61) 3245 6218

Copyright 2019 - Brazilian Thoracic Association

Logo GN1