red Obesity is becoming a pandemic, which is alarming because virtually all internal organs and systems are involved in the pathological process. The explanation is simple: adipose tissue is a source of hormones that control human eating behavior. For example, leptin is closely affiliated with metabolism, which means it has a connection to many bioactive substances. Thus, overeating or malnutrition become triggers for a multitude of pathologies, including the respiratory system. We are talking about obesity-associated hypoventilation syndrome, or Pickwick’s syndrome, to which this article is devoted.
Contents:
- What is Pickwick syndrome.
- The relationship between apnea and Pickwick syndrome.
- Role of leptin.
- Obesity and hypoventilation.
- Two groups of obese patients.
- Diagnosis of Pickwick syndrome.
- Treatment of hypoventilation.
What is Pickwick’s Syndrome
This pathological condition is commonly understood as chronic pulmonary hypoventilation in obese patients with BMI > 30 kg/m2 and hypercapnia of RAS2 > 45 mmHg, unexplained by anything other than significant weight gain. At the same time, despite the fact that theoretically hypoxemia does not always accompany hypercapnia, but the practical blood oxygen saturation is reduced in such patients. Another feature of leptin hypoventilation is nocturnal apnea. However, there may only be respiratory disturbances of a central nature. One does not exclude the other.
The connection between apnea and Pickwick syndrome
If you look closely at the obese sleepy servant Joe from the novel by Dickens, after whom Pickwick syndrome is named, it is clear that he has severe chronic respiratory failure with nocturnal apnea syndrome. This has allowed some to consider both pathologies synonymous, and others – to allocate apnea as an independent symptom of obesity. The truth, as always, is somewhere in the middle. On the one hand, we see many patients with manifestations of both chronic respiratory failure and nocturnal apnea, and on the other hand, even very severe obstructive apnea is not always accompanied by chronic hypoventilation.
The pathophysiology of obesity, which provokes hypoventilation, appears to be a combination of limited pulmonary ventilation, impaired respiratory mechanics, chronic fatigue of respiratory muscles and failure of central mechanisms of respiratory regulation. In other words, all the above triggers become triggers of chronic hypercapnia.
The role of leptin
Recently, the role of leptin in the development of hypoventilation in obesity has received considerable attention. The adipose tissue hormone responsible for satiety is a regulatory polypeptide. Since in the hypothalamus, through the centers of which leptin controls human eating behavior, the nuclei controlling eating and breathing are located side by side, they are activated under hypoxic conditions almost simultaneously, increasing respiratory sensitivity to high blood CO2 concentrations.
Normally, the increased level of the fat cell hormone in overweight patients provokes increased lung ventilation, which is regarded as a protective mechanism, allowing overweight patients to maintain normal RAS2 levels. In contrast, a higher concentration of leptin in the bloodstream in chronic hypercapnia does not lead to an adequate increase in lung ventilation. This means that low individual sensitivity of respiratory receptors to leptin is a probable mechanism of underventilation syndrome on the background of extra kilograms.
Obesity and hypoventilation
One of the features of the hypoventilation syndrome against the background of obesity is an increase in respiratory distress at night. This is explained by the fact that upper airway obstruction is exacerbated by abdominal fat pressure on the diaphragm when lying down. Plus – uncontrolled breathing in sleep with minimal receptor sensitivity to hypoxia and hypercapnia on the background of decreased tone of respiratory muscles. Apparently, the connection between apnea and leptin hypoventilation as a result of obesity exists, but it is ambiguous with a complex physiological mechanism.
On the one hand, obesity is a trigger of apnea, on the other hand, it stimulates the development of metabolic dysfunction, such as diabetes mellitus 2. This is the so-called vicious circle, in which apnea provokes a disorder of carbohydrate metabolism, which in turn leads to obesity, hypoventilation and in parallel aggravates obstructive breathing at night. In addition, hypoventilation impairs gas exchange, stresses respiratory function, musculature, and further reduces the sensitivity of the respiratory center to hypercapnia and hypoxemia. It turns out that the severity of obstruction helps to form chronic respiratory failure faster.
The following should be noted: chronic hypoventilation is formed against the background of overweight, but BMI itself has little effect on chronic respiratory failure. Moreover, in patients with hypercapnia, which occurs in the daytime, the situation worsens by night, and the value of RAS2 in the daytime correlates with the severity of nocturnal obstruction. In addition, respiratory failure against the background of obesity is heterogeneous in nature in different patients, so the correction of Pickwick’s syndrome is also variable.
Two groups of obese patients
Patients with background hypoventilation syndrome and nighttime apnea are thought to fall into two large groups:
- Apnea-dependent;
- Apnea-independent.
If the first in the development of chronic respiratory failure can easily normalize gas exchange by eliminating nocturnal apnea, the latter need a combined treatment with drugs of different pharmacological groups. In this case, chronic hypoventilation and nocturnal airway obstruction are associated with each other, but are separate syndromes.
There are no exact statistics on the prevalence of hypoventilation syndrome against obesity, but indirectly we can speak about less than 1% Pickwick’s syndrome in patients with obstructive apnea at night. However, clinical observations suggest that hypoventilation is a major trigger of chronic hypercapnia.
Diagnosis of Pickwick’s Syndrome
To suspect the pathology is quite simple clinically. A patient with pronounced obesity, shortness of breath on physical exertion, a constant feeling of brokenness, sleepiness, with anxious sleep accompanied by snoring, headaches in the morning, memory impairment. On physical examination, cyanosis and often pastosity of the legs attract attention. At the same time, pronounced tachypnea in such a patient may be absent, and a slight increase in respiratory rate does not correspond to the severity of respiratory failure. It turns out that patients not only can not, but also do not want to breathe.
In the general blood test there is secondary erythrocytosis.
Analysis of acid-base balance and blood gas composition gives typical symptomatology:
- ompensated respiratory acidosis;
- hypercapnia;
- hypoxemia.
Instrumental techniques show minimization of pulmonary volumes, pulmonary hypertension, hypertrophy of right heart chambers with their subsequent dilation. Sleep apnea syndrome with significant hypoxia, sometimes with oxygen saturation below 50% is detected. In the absence of obstruction during sleep, hypoventilation is noted. Unfortunately, noninvasive techniques of CO2 level monitoring during sleep are not widely used in Russia, therefore a simple criterion for diagnosing hypoventilation is used: the registration of hypoxemia with oxygen saturation <90% lasting >5 minutes, with minimum SpO2 value during this period ≤85% in the absence of obstructive respiratory disorders.
Although the development of chronic pulmonary heart failure in the absence of adequate treatment is considered a typical complication of obesity-associated hypoventilation syndrome, the diagnosis of chronic heart failure in such patients is not always obvious.
Dyspnea in this case is not a marker of congestion in the small circle of circulation, but the result of increasing pressure of abdominal fat on the diaphragm in the horizontal position. Swelling is the result of excess weight, varicose veins and lymphostasis, so the prescription of diuretics in this case is not always unreasonable. The consequence of such treatment is metabolic alkalosis, which automatically provokes accumulation of CO2.
Treatment of hypoventilation
To correct hypoventilation against the background of obesity, respiratory analeptics are used, the most promising among which are Medroxyprogesterone and Acetazolamide. The first one increases sensitivity of the respiratory system to hypercapnia, which leads to the increase of pulmonary ventilation, decrease of RAS2 and increase of ROS2, which explains the frequent prescription of the drug in patients with chronic hypoventilation. But it should be remembered that such therapy is fraught with the risk of thrombosis and thromboembolism due to the fact that blood viscosity is a priori changed due to obesity, so in many cases the drug prescription is not always justified.
Acetazolamide is a diuretic that inhibits carboangidase, which induces metabolic acidosis. This, in turn, potentially stimulates respiration and leads to reduction of RAS2, but in practice the therapeutic value of this is minimal. The main recommendation for use in alveolar hypoventilation is pastosity in patients with decompensated pulmonary heart. Although the diuretic effect of Acetazolamide is minimal, in combination with loop diuretics it can compensate the alkalosis caused by them.
It seems that the problems of pathology can be solved by prescribing oxygen, but this is a mistake, because the carbon dioxide content in the blood is not taken into account. In practice, this mistake is often made because oxygen saturation data are used to diagnose leptin hypoventilation. More complex analysis of gases is abandoned because of the simplicity of determining saturation. And the regulation of breathing is normally correlated with the concentration of CO2, and oxygen has little effect on respiratory parameters.
At normal RAS2 concentration only minimization of blood oxygen saturation less than 60 mm Hg significantly increases lung ventilation. And in patients with chronic hypoventilation the control of respiration is completely focused on blood oxygen content. It turns out that administration of inhaled oxygen during spontaneous breathing leads to even greater fall of ventilation. Thus, oxygen therapy based only on hypoxemia correction in such patients can aggravate respiratory failure up to hypercapnic coma with fatal outcome.
Treatment of obesity is a strategic goal for patients with pulmonary hypoventilation. Radical shedding of extra pounds can correct pulmonary ventilation and eliminate nocturnal apnea. But it is necessary to understand that any radical methods will not provide immediate results. Besides, it is not easy to fight obesity on your own, and surgical interventions are dangerous. True, this does not exclude bariatric surgery from the arsenal of means for correcting obesity. In any case, the treatment of hypoventilation against the background of obesity is a difficult task.
Today, the first-line treatment is noninvasive or mask ventilation, which minimizes the strain on respiratory muscles, improves breathing and restores respiratory center sensitivity to CO2, while ensuring upper airway patency at night. This not only improves quality of life, but also minimizes mortality among these difficult patients.
Therapy should begin with CPAP ventilation – breathing with constant positive air pressure. This will eliminate the obstruction of the respiratory tract at night and compensate for its patency. But CPAP therapy is suitable only for a proportion of patients with hypoventilation syndrome due to obesity. The combination of CPAP and oxygen therapy is considered the wrong tactic because it eliminates hypoxia but not hypoventilation.
CPAP ventilation is indicated in patients with severe nocturnal apnea and moderate gas exchange abnormalities during the day. If CPAP therapy fails, classical non-invasive assisted ventilation is prescribed: the delivery of machine breaths is synchronized with the patient’s own breathing.
It turns out that in acute hypercapnia, noninvasive ventilation is considered an established therapy and is widely used. In patients with chronic hypoventilation such support is unreasonably rarely used. It can effectively rehabilitate patients and return them to active life.
