Congenital rubella syndrome (CRS) causes potentially fatal birth defects in infants and is caused by infection of the pregnant mother with the rubella virus. Although a rare disease in the developed world, rubella remains endemic in many parts of the world with 100,000 infants born with CRS annually.1 The disease is not foreign to the United States. The global rubella pandemic of the early 1960s, predating vaccine use, resulted in 20,000 infants born with CRS in the United States.2 Currently, the number of reported cases of CRS in the United States is <1 per year, with most cases occurring in mothers born abroad and not vaccinated. Although CRS patients present for medical attention and undergo corrective surgery in infancy, manifestations of CRS continue into adulthood. With written permission from our IRB, we present a case of an adult patient with CRS who had an unexpected prolonged postoperative respiratory insufficiency.
A 30-year-old, deaf, mute, and early osteoporotic woman suffering with bipolar disorder and CRS presented for vocal cord lateralization and tracheostomy. The patient originally presented for repair of a residual tracheocutaneous fistula after tracheostomy 2 years earlier. The surgeon’s preoperative evaluation revealed limited mobility of the left vocal cord, an immobile right vocal cord, and glottic stenosis. The tracheocutaneous fistula persisted as a breathing conduit due to vocal cord disease suggestive of neurologic etiology. Of note, the patient had a history of a similar surgery on her vocal cords, with tracheostomy, at the age of 12 years, the details of which could not be located. Two years prior, she developed acute respiratory failure after a psychiatric episode treated with benzodiazepines requiring mechanical ventilation culminating in tracheostomy. She was eventually discharged with compensated respiratory acidosis, attributed to weakness, necessitating nocturnal ventilatory support at home. Workup at the time showed normal thyroid function tests, normal liver enzymes, abnormal coagulation studies (prothrombin time, 28 seconds; international normalized ratio, 2.2; partial thromboplastin time, 46 seconds), and negative acetylcholine receptor antibodies.
Preoperative pulmonary evaluation revealed normal pulmonary function tests with mild hypoxemia and respiratory acidosis; pH 7.38 to 7.27, PO2 92 to 68 mm Hg, PCO2 58 to 73 mm Hg, base excess +6 to 5 mmol/L at rest and during pulmonary function tests, respectively. The pulmonologist noted that the patient was somnolent and her hemoglobin oxygen saturation decreased when she fell asleep. She attributed these findings to 1 of her psychiatric medicationsa which included fluoxetine 40 mg, risperidone 2 mg, and tegretol XR 200 mg. The patient was advised to decrease the dose of psychiatric drugs and to use incentive spirometry. Chest radiograph only revealed scoliosis.
The patient presented to surgery 4 months after her initial surgical clinic visit without any further testing. She was 155 cm tall and weighed 68 kg. She had decreased breath sounds bilaterally with diminished breathing effort. After standard monitors were applied, anesthesia was induced using midazolam 2 mg, propofol 90 mg, vecuronium 3 mg, and fentanyl 100 µg and maintained with sevoflurane. The duration of surgery was 2 hours, during which she received a total 250 µg of fentanyl, with the final 50 µg dose administered 20 minutes before the end of surgery. Neuromuscular blockade was reversed using glycopyrrolate 0.65 mg and neostigmine 4.5 mg after a train-of-four count 4/4 at the abductor pollicis. The patient was arousable at the end of surgery, breathing spontaneously through a cuffed tracheostomy tube, but required repeated stimulation to keep her from drifting into sleep and hypopnea. She was transferred out of the operating room 30 minutes later. No arterial blood gases were obtained at the time.
In the postanesthesia care unit, the patient became unresponsive with respiratory depression requiring mechanical ventilation. Arterial blood gas revealed profound respiratory acidosis (pH 7.13/PCO2 107 mm Hg/PO2 315 mm Hg/HCO3 35 mmol/L/BE +3 mmol/L/98.6%). Her respiratory depression, at the time, was attributed to the residual effect of fentanyl. Naloxone was not given because, once her lungs were ventilated through the tracheostomy tube, the patient became arousable; it had been an hour since the last dose of fentanyl and she was expected to recover soon. However, somnolence requiring continued ventilator support persisted for several additional hours and she was transferred to the intensive care unit (ICU) where she remained for a week. The patient had poor respiratory effort with negative inspiratory force of −10 cm H2O and tidal volumes of 50 to 100 mL prompting further investigation of her acute and chronic respiratory insufficiency. Testing included thyroid function tests, aldolase, and creatine kinase; the results of these tests were all normal. The patient’s electrolytes revealed hypophosphatemia that was corrected without any improvement in respiratory insufficiency. Magnetic resonance imaging of the cervical spine and brain revealed an old right lacunar basal ganglia infarct with no acute changes.
The ICU stay was complicated on day 5 by tracheal obstruction due to blood clots, which were removed by bronchoscopy and sent for cytology and microbiology testing. Subsequently, her respiratory variables improved. Bacterial, fungal, and viral (human immunodeficiency virus, adenovirus) tests were all negative. Diaphragm fluoroscopy showed adequate spontaneous movement. Ventilatory support was discontinued 7 days postoperatively, and the patient was discharged home with a tracheostomy tube in place.
A follow-up visit 1 week after hospital discharge showed persistence of chronic respiratory acidosis (pH 7.31/PCO2 63 mm Hg/PO2 71 mm Hg/HCO3 31 mmol/L/BE +3 mmol/L/94%). Pulse oximeter oxygen saturation (SpO2) was 98% at rest and 92% after ambulation. Her chronic hypoventilation was attributed to a central nervous system process caused by congenital rubella.
The major concern with rubella infection is its teratogenic effect on the fetus, first observed in 1941 by Gregg.3 CRS is used to denote any combination of the findings known to result from gestational rubella.4 Classical CRS is characterized by the combination of cardiac, ocular, and hearing defects, although rubella virus in a fetus can affect almost any organ.4,5 There are many manifestations of CRS, but those of greatest importance in our patient were associated with central nervous system injury.
Bilateral vocal cord paralysis (VCP) and central hypoventilation are suggestive of brainstem dysfunction and vagus nerve abnormality that may be caused by congenital rubella (meningoencephalitis or stroke). VCP refers to vocal cord immobility due to disruption of the motor nerve supply to the larynx.6,7 VCP may result in long-standing airway obstruction and act as the primary culprit causing hypoventilation. However, VCP was excluded as the primary cause of hypoventilation since, despite corrective surgery and a tracheostomy tube, the patient continued to have respiratory acidosis on postoperative follow-up.
Central hypoventilation syndrome is a rare neuropathologic condition characterized by an inadequate central respiratory drive with a decreased response to PaCO2 resulting in hypoventilation, apnea, hypercarbia, and hypoxemia. This syndrome is characterized by hypoventilation that worsens during sleep.8 It may be congenital or acquired. The congenital form, also known as Ondine’s Curse, is seen in infancy. Acquired central hypoventilation results from lesions affecting the medullary centers controlling respiration (brainstem infarction, hemorrhage, encephalitis, demyelinating diseases, and nonspecific anoxic insult).9 A diagnosis may be delayed due to lack of awareness of this disease, particularly in milder cases. Given the patient’s history of nocturnal ventilatory support after previous hospital admission, her persistent hypercarbia, and sensitivity to benzodiazepines and opioids, the diagnosis of central hypoventilation syndrome is very likely. Ideally, a polysomnographic study should have been done to confirm diagnosis.
Unfamiliarity with CRS and central hypoventilation syndrome resulted in a misdiagnosis of the patient by health care professionals on previous encounters and hospitalizations. Hypersensitivity to anesthetic drugs, central hypoventilation with chronic respiratory acidosis, and airway obstruction by blood clots all led to difficulty in separating the patient from mechanical support.
With myriad clinical manifestations and various corrective surgical options, the perioperative care of CRS can be challenging. The type of anesthesia, choice of muscle relaxants, analgesics, sedatives, and perioperative care are influenced by how the CRS is manifested in the patient in terms of cardiovascular, musculoskeletal, neuronal, metabolic, endocrine, and renal dysfunction. Thus the preanesthetic workup should include a detailed history and physical examination, a listing of prior surgeries and hospitalizations, and laboratory testing appropriate to the specific abnormalities suspected as well as those of specific interest depending on the planned surgery. For bilateral VCP and hypoventilation, a magnetic resonance imaging of the brain and cervical spine, fluoroscopy of the diaphragm, vocal cord electromyogram, polysomnography, and tests for infectious etiology (i.e., human immunodeficiency virus, hepatitis, meningitis, encephalitis) should be obtained. These tests may help detect and treat a reversible cause preoperatively, adjust intraoperative anesthetic plan, and anticipate postoperative needs such as postanesthesia care unit stay, monitoring, ventilatory support, and disposition.
Anesthetic goals involve minimizing respiratory depression to avoid prolonged mechanical ventilation. For general anesthesia, it is necessary to intubate the patient’s trachea and control lung ventilation, because these patients may not breathe spontaneously when asleep.10 Judicious use of anesthetics with short duration of action is preferred. Because prolonged respiratory depression and hypoventilation with delayed exhalation of inhaled anesthetics may occur, total IV anesthesia with propofol and remifentanil has been suggested for patients with central hypoventilation.10 Patients with pulmonary hypertension due to chronic hypercarbia and hypoxemia may be predisposed to heart failure and arrhythmias, and appropriate management is indicated.11,12
In this case report, we describe a rarely seen central hypoventilation syndrome and VCP associated with CRS. A more complete medical history with thorough preoperative testing including polysomnography as well as intraoperative avoidance of benzodiazepines and smaller doses of opioids might have resulted in an outcome minimizing the prolonged postoperative course including that in the ICU. Perioperative communication among the anesthesiologist, surgeon, and consulting physicians managing these patients is essential.
a eHealthMe. Tegretol and Hypoventilation: a study of 23 users. Available at: http://www.ehealthme.com/ds/tegretol/hypoventilation. Accessed March 26, 2013.
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