Central alveolar hypoventilation and failure to wean from the ventilator.

A 66-year-old woman was transferred to our respiratory care unit for “failure to wean” from the mechanical ventilator. Initially admitted to another hospital for worsening headaches and nausea, she awoke with dysphagia, dysphonia, hypothermia (body temperature 93°F), and sinus bradycardia (heart rate ∼40); she was later found to be apneic and required intubation for hypercapnic respiratory failure. Personnel at the other hospital attempted twice to extubate the patient, but she was unable to clear her secretions and developed hypercapnia, leading to transfer to our facility for further management. Medical history included smoldering myeloma, migraine headaches, and hypothyroidism. Her thyrotropin stimulating hormone (TSH) level was normal. Arterial blood gas (ABG) drawn while the patient was awake revealed a mildly elevated PCO2 of 45, but, during sleep, the level increased to the mid-60s. Of note, the patient was able to normalize her daytime PCO2 by voluntarily increasing her ventilation. She also had periodic apneas while sleeping, triggering ventilatory alarms while she was on pressure-support mode and, therefore, requiring a back-up rate. She also had significant bradyarrhythmias during sleep, with sinus pauses of approximately 4 seconds. The patient had a tracheostomy tube, through which she was ventilated during the night and that was corked during the day. Except for dysphonia and bilateral Babinski signs, the neurologic examination, including the cranial nerves and cerebellar exam, revealed no abnormalities. The findings of the chest radiograph and maximal respiratory pressures performed at the bedside were normal. Electromyogram of the diaphragm and phrenic nerves revealed no evidence of a neuromuscular disorder. A central cause for hypoventilation was suspected; a brain magnetic resonance imaging scan revealed abnormal, bilateral, symmetric T-2 hyperintensities within the lateral medulla (Figure 1) with no clear cause. Figure 1 Presence of abnormal, symmetrical, bilateral lesions in the lateral medulla (white arrow). What is the diagnosis? Answer: Acquired central alveolar hypoventilation due to bilateral medullary lesions Congenital central alveolar hypoventilation is a rare but severe condition that usually affects infants. The syndrome is characterized by hypoventilation that is worse during sleep than wakefulness and is unexplained by primary pulmonary, neurologic, or metabolic disease.1–3 The hypoventilation is often worse during non-rapid eye movement (NREM) sleep than during rapid eye movement (REM) sleep because the control of breathing is entirely metabolic during NREM sleep.4 Patients with congenital central hypoventilation syndrome also have abnormalities of autonomic nervous system function, such as Hirschsprung disease. A suspected diagnosis of congenital central hypoventilation syndrome is confirmed by genetic testing for mutations in the PHOX2b gene.5,6 Acquired central alveolar hypoventilation has similar clinical features and reportedly results from lesions affecting the medullary centers that specifically control respiration.7, 8 The acquired form has been reported to occur secondary to brainstem infarction, hemorrhage, encephalitis, demyelinating diseases, and nonspecific anoxic insult.7 Ventilatory support at night may correct the hypoventilation; however, patients with severe manifestations may require ventilatory support during the day as well. Medications such as acetazolamide, levothyroxine, and clomipramine have been tried with minimal clinical benefit. Due to the precarious position of the medullary lesions in our patient, biopsies were not performed. She developed pancytopenia and was treated with cyclophosphamide and intravenously administered methylprednisolone after the diagnosis of multiple myeloma was confirmed. The bilateral medullary lesions were assumed to be related to myeloma and improved with chemotherapy. Though the symptoms of dysphagia and dysphonia improved, the hypoventilation and sinus bradycardia persisted while the patient was asleep. Central sleep apnea was documented by a split-night overnight polysomnogram with the tracheostomy tube corked. The apnea-hypopnea index (AHI) was 83 per hour. The very high AHI appeared to be due to repetitive short central apneas (Figure 2A). This was treated with a bilevel positive pressure airway device with a spontaneous timed (BPAP-ST) mode (Figure 2B). Because the patient's symptoms responded very well to BPAP-ST (Figure 2B) with a back-up rate of 14 breaths per minute, the tracheostomy tube was removed before the patient was transferred to a skilled nursing facility for further care and rehabilitation. Figure 2 (A) Compressed diagnostic portion of the polysomnogram focusing on the respiratory and electrocardiogram (ECG) channels (120-s epoch) showing repetitive short central apneas associated with bradyarrhythmias. A breathing pattern of closely grouped series ...