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Table of Contents   
CASE REPORT  
Year : 2017  |  Volume : 10  |  Issue : 4  |  Page : 1049-1053
Central hypoventilation syndrome and hypoxic drive disorder


1 Gorgan Congenital Malformations Research Center, Department of Internal Medicine, Golestan University of Medical Science, Gorgan, Iran
2 Department of Internal Medicine, Golestan University of Medical Science, Gorgan, Iran
3 Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Science, Gorgan, Iran

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Date of Web Publication5-Oct-2017
 

   Abstract 


The central hypoventilation syndrome is a rare disease which is mainly characterized by respiratory failure in response to hypercapnia and hypoxia. Patients need some levels of ventilation support during sleep or even during the day. This study introduces a young Turkmen male patient with central hypoventilation suffering from the loss of consciousness and severe drowsiness.

Keywords: Central hypoventilation syndrome, hypercapnic respiratory failure, hypoxic drive disorder

How to cite this article:
Zahedi M, Keshavarz B, Montazery M, Shahmirzadi AR. Central hypoventilation syndrome and hypoxic drive disorder. Ann Trop Med Public Health 2017;10:1049-53

How to cite this URL:
Zahedi M, Keshavarz B, Montazery M, Shahmirzadi AR. Central hypoventilation syndrome and hypoxic drive disorder. Ann Trop Med Public Health [serial online] 2017 [cited 2019 Sep 21];10:1049-53. Available from: http://www.atmph.org/text.asp?2017/10/4/1049/215864



   Introduction Top


Air hemostasis control requires the integration of various components including the normal functions of the central and peripheral nervous systems, the upper healthy airways, and the enough strength of the musculoskeletal system. Normally, ventilation and respiration are performed by respiratory centers in the pons and medulla through central and peripheral chemical receptors. Respiratory control centers regulate changes in pH, PcO2, and PO2 through ventilation. Impairment in central control can cause acquired or congenital hypoventilation, hypercarbia, and hypoxia.

Central alveolar hypoventilation syndrome is a rare disorder which refers to the increased serum concentration of CO2 gas in arterial blood due to inadequate gas exchange.

This disease was first described by Richter et al., in 1957.[3] In 2006, only 200 cases of this disease were reported worldwide.

This syndrome can occur in infancy or later in life. Regardless of the age of onset, it includes patients who suffer from respiratory failure in response to severe hypoxia and hypercapnia.

The secondary symptoms of hypoventilation syndrome are often nonspecific. Left untreated, these patients face complications such as severe hypercapnia, hypoxia, cyanosis, heart failure, convulsion, and death.

In addition, severe hypercapnia may cause asterixis, myoclonus, and papilledema due to the increased intracranial pressure. Patients with central alveolar hypoventilation do not usually make any complaints although they may experience the symptoms of sleep disorders and hypersomnolence during the day. In general, diagnosis is possible only on the basis of respiratory failure.

The early diagnosis and ventilation supports prevent these problems. Nearly all of such patients need mechanical ventilation supports during sleep; however, some of them need respiratory supports even during the day.[1],[2],[3],[4],[5]

Given the fact that this syndrome is rare and interesting, this study introduces a young Turkmen male patient with central alveolar hypoventilation of hypoxic drive disorder with the loss of consciousness and severe drowsiness.


   Case Report Top


A 31-year-old Turkmen male patient was under the treatment of a cardiovascular and hematological center with cardiomyopathy and polycythemia diagnosis for 3 years. He was transferred to the emergency room because of severe drowsiness and a loss of consciousness.

The patient's sister mentioned drowsiness and tremor 3 days before referral. These symptoms became severe on the morning of referral. She did not mention anything about misusing drugs or opium, smoking, and taking specific medicines.

The patient's companions said that he had experienced a progressive loss of the ability to work, some bruises, and snores during sleep.

Upon his arrival, the thin patient had severe central and peripheral cyanosis as well as severe drowsiness and breathed slowly.

Patient blood pressure was 140/90 mmHg, pulse rate was 110/min, respiratory rate was 8/min, T: 36 °c and SpO2: 67%.

In the initial examinations, there were no noticeable problems, especially in the auscultation of the lungs and heart (RVS3).

In neurological examinations, there were no considerable issues, except for the loss of muscular power. In electrocardiogram, there was some evidence in favor of right axis [Figure 1].
Figure 1: ABG pH: 7.15 HCO3: 46.15 PCO2: 120 PO2: 22

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Upon the initiation of mechanical ventilation, a urine screen test (multidrug) was requested for morphine, methadone, tramadol, tricyclic antidepressants, marijuana (tetrahydrocannabinol), phenobarbital, barbiturates, and benzodiazepines. The test results were negative.

Then, complete blood count was requested to evaluate the polycythemia status, and blood urea nitrogen/creatinine was tested to assess kidney disorders, liver aminotransferases, bilirubin, prothrombin time (PT), and albumin to investigate hepatic insufficiency.

In the initial examinations, hemoglobin and hematocrit were reported 20 and 50 mg/dl, respectively. An ultrasound examination was requested to exclude polycythemia vera by determining the sizes of liver and spleen and investigating jak2-V617F mutation. The sizes of liver and spleen were normal, and the mutation was reported negative.

According to the test results and adequate urine flow, renal failure was not concluded.

Then, severe pulmonary hypertension (Pul HT), severe right ventricular (RV) failure, and corpulmonale were raised; however, there was no evidence of cardiac valvular disease.

Patient's Chest X-Ray (CXR) showed mild to moderate Cardiomegaly and Prominence of right lung hilum [Figure 2].
Figure 2: Patient's chest X-ray evidence

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Aminotransferase abnormalities, PT, and international normalized ratio were justified regarding hepatic congestions, and phlebotomy was carried out with respect to the high Hb concentration.

A computed tomography (CT) scan of the brain and spiral chest were requested; however, no pathological issues were found [Figure 3] and [Figure 4].
Figure 3: Brain computed tomography scan

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Figure 4: Spiral computed tomography scan

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Considering respiratory failure, hypoxic drive loss, and all of the above-mentioned findings, the central hypoventilation syndrome was concluded. Then, a magnetic resonance imaging (MRI) was conducted to examine the secondary cerebral causes more accurately. The results are as follows:

Technique: T2 and Fluid-attenuated inversion recovery/diffusion-weighted imaging/apparent diffusion coefficient

Three micro lesions with restricted diffusion were notable at right cerebral hemisphere, which are suggestive for lacunar infarctions.

These findings justify the patient's conditions. Considering drowsiness and the loss of consciousness, the hypoxic encephalopathy was raised. When hypercapnic respiratory failure was diagnosed, the patient was under mechanical ventilation. After improving consciousness, he was extubated and placed under noninvasive ventilation (NIV), ResMed.

These findings justify the patient's conditions. Considering drowsiness and the loss of consciousness, the hypoxic encephalopathy was raised. When hypercapnia respiratory failure was diagnosed, the patient was under mechanical ventilation. After improving consciousness, he was ex-tubed and placed under (Noninvasive Ventilation) NIV (with: I PAP: 14 mmHg, E PAP: 5 mmHg, RR: 12/min). RR: 12/min.

Then, the patient's dyspnea and orientation improved gradually; however, PCO2 increased, and PO2 returned when NIV was removed.

After the patient's general status was improved, spirometry was conducted. There were no restrictive and obstructive patterns detected. The voluntary hypoventilation test decreased PCO2 to 40.

The patient's hypoxia and hypercapnia were intensified during sleep; however, NIV could control them.

Finally, the patient was diagnosed with the central hypoventilation syndrome and the loss of hypoxic drive. Then, he was discharged under treatment with the NIV device and also trained in the continuous use of medicine. He was asked to come back every 6 months for follow-up.

Now, after 6 months, his latest test results are as follows:

Arterial blood gas

Arterial blood gas examination revealed PH: 7/39, PCO2: 50 mmHg, HCO3: 36 mmol/L, PO2: 80 mmHg.

Currently, the patient uses the NIV device every 2 h, then he takes a rest for 1 h. He does not have any problem doing his routines. In his last echo test, mild pulmonary HTN and mild RV failure were decreased, and EF was 50%–55%.


   Conclusion Top


Hypoventilation refers to the increase in the serum concentration of CO2 gas in arterial blood due to the inadequate gas exchange.[1],[6] The diseases causing hypoventilation and increased dead space are divided into four groups including lung and chest parenchyma, sleep apnea, neuromuscular diseases, and hypoxic drive disorders.[7]

The hypoxic drive disorder is secondary to neuromuscular diseases. The patient in this case suffered from this disease.

The chronic alveolar hypoventilation is characterized by the decreased arterial pressure of oxygen (Pao2) and increased pressure of carbon dioxide (Paco2).

The secondary symptoms of hypoventilation are often nonspecific. In the initial steps, there may be no signs such as hypoventilation with different causes of neuromuscular disorders or chest wall disorders, in which PaO2 and PaCO2 are normal. Following the nightly hypoventilation during rapid eye movement sleep, vital capacity drops gradually and hypercapnia increases. Then, there will be the signs of respiratory acidosis and increased plasma concentrations of bicarbonate. Increased PaCO2 will decrease PaO2 and hypoxia. If hypoxia is intensified, there will be cyanosis, Q erythropoietin stimulations, and the production of secondary erythrocytosis, which is the chronic hypoxia and hypercapnia. Then the increased vasoconstriction will cause the induced pulmonary hypertension, the right ventricular hypertrophy and failure.[5],[7]

The clinical manifestations of hypoventilation include exertional dyspnea and even at rest (the most common symptom), dyspnea during daily activities, fatigue, oversleeping, poor sleep, orthopnea, morning headaches, coughs, anxiety, and psychological disorders. Other symptoms of the deterioration of hypoventilation include anxiety progressing to delirium, confusion, and increasing drowsiness, which is known as carbon dioxide unconsciousness.[6]

In this study, the patient mentioned severe drowsiness and the loss of consciousness 3 days before referral.

Physical examinations, imaging procedures (CXR, MRI, and CT scans), and pulmonary function test lung functional tests can be used to identify the causes of central hypoventilation in detail. If the respiratory system (lungs, airways, and chest wall) is not responsible for the chronic hypercapnia, the cause must be sought in hypoventilation resulting from hypoxic drive and neuromuscular disorders. In the hypoxic drive disorders, there are signs of slight increases in ventilation in response to the high level of CO2 and decreased O2. These diseases are hard to diagnose. It can be suspected when a patient with hypercapnia has normal strengths of respiratory muscles, normal lung function, and normal arterial-alveolar PO2. Hypoventilation is characterized by decreased hypoxic drive during sleep indicating polysomnography very often.[7]

Other methods of measuring central hypoxic drive include the use of chemical stimuli such as hypoxia, hypercapnia, and mouth occlusion technique. CT scan and brain MRI can also indicate structural abnormalities in the pons or medulla decreasing the volume of breathed air and hypoventilation. On the other hand, the chronic or hypothyroidism use of drugs can decrease hypoxic drive and chronic hypercapnia.[8]

The nightly noninvasive positive pressure ventilation (NIPPV) was successful in the treatment of central hypoventilation. It had some effects on the patients with chest wall and neuromuscular functioning disorders. Nightly NIPPV is used to improve hypercapnia during the day and increase the quality of life. If NIPPV fails, mechanical ventilation is required.

A systematic study indicated that mechanical ventilation improved lung mechanism, respiratory muscular power, and hypoxic drive. In the long term, it reduces the symptoms. Currently, the case patient used NIV every 2 h. Then, he takes a rest for 1 h. The quality of his life has been improved.[9],[10],[11]

The cause of metabolic alkalosis in patients with hypoventilation should be corrected because increasing the plasma concentration of bicarbonate higher than the chronic respiratory acidosis can intensify hypoventilation.

It appears that oxygen therapy can be effective in patients with hypoxia, polycythemia, and pulmonary HTN. However, this treatment worsens hypercapnia in some other patients.[7],[12]

Other therapeutic actions, meant for patients with hypoventilation, include glossopharyngeal respiration and pacing aperture to increase ventilation. Some studies indicated that the use of mouth and throat muscles were effective in improving ventilation in the short term when mechanical ventilation was not employed. Phrenic nerve surgery or aperture pack can be regarded as the potential treatment for patients with hypoventilation suffering from the lesions of the cervical spine and respiratory drive disorders. All these factors indicate that aperture pack can improve the quality of life significantly.

It is expected that patients with central alveolar hypoventilation can reach the desirable quality of life and have a normal lifetime with clinical interventions and regular follow-ups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Richter T, West JR, Fishman AP. The syndrome of alveolar hypoventilation and diminished sensitivity of the respiratory center. N Engl J Med 1957;256:1165-70.  Back to cited text no. 1
    
2.
Murphy PB. Physiological Assessment of the Load-Capacity-Drive Relationship in Chronic Respiratory Failure and Outcomes Following Domiciliary Non-Invasive Ventilation: King's College London; 2015.  Back to cited text no. 2
    
3.
Katz ES, McGrath S, Marcus CL. Late-onset central hypoventilation with hypothalamic dysfunction: A distinct clinical syndrome. Pediatr Pulmonol 2000;29:62-8.  Back to cited text no. 3
    
4.
Lee P, Su YN, Yu CJ, Yang PC, Wu HD. PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: Presentation from newborn to adulthood. Chest 2009;135:537-44.  Back to cited text no. 4
    
5.
Barratt S, Kendrick AH, Buchanan F, Whittle AT. Central hypoventilation with PHOX2B expansion mutation presenting in adulthood. Thorax 2007;62:919-20.  Back to cited text no. 5
    
6.
Kennedy JD, Martin AJ. Chronic respiratory failure and neuromuscular disease. Pediatr Clin North Am 2009;56:261-73, xii.  Back to cited text no. 6
    
7.
Fauci AS. Harrison's Principles of Internal Medicine. New York, USA: McGraw-Hill Medical Publishing Division; 2008.  Back to cited text no. 7
    
8.
Susło R, Trnka J, Siewiera J, Drobnik J. Ondine's Curse - Genetic and Iatrogenic Central Hypoventilation as Diagnostic Options in Forensic Medicine. Adv Exp Med Biol 2015;861:65-73.  Back to cited text no. 8
    
9.
Macey PM, Alger JR, Kumar R, Macey KE, Woo MA, Harper RM. Global BOLD MRI changes to ventilatory challenges in congenital central hypoventilation syndrome. Respir Physiol Neurobiol 2003;139:41-50.  Back to cited text no. 9
    
10.
Atkins GT, Gifford AH. Quality of Life during Long-Term Mechanical Ventilation in Hypercapnic Respiratory Failure: Main Determinants and Evidence. In: Esquinas A. (eds) Noninvasive Mechanical Ventilation. Springer, 2016; p. 859-65.  Back to cited text no. 10
    
11.
Kelly JL. Autotitrating Non-Invasive Ventilation (NIV) in Patients with Hypercapnic Ventilatory Failure: Imperial College London; 2015.  Back to cited text no. 11
    
12.
Cain SM. Increased oxygen uptake with passive hyperventilation of dogs. J Appl Physiol 1970;28:4-7.  Back to cited text no. 12
    

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Correspondence Address:
Arash Rezaei Shahmirzadi
Golestan University of Medical Sciences, Gorgan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ATMPH.ATMPH_249_17

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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