Long-term mechanical ventilation in a pregnant woman with amyotrophic lateral sclerosis: a successful outcome

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motoneurons, which results in progressive muscle weakness, hyperreflexia, spasticity, and muscular atrophy [1]. Respiratory failure is the most common cause of death in ALS. However, it is not clear if pregnant women with ALS are at an increased risk of developing respiratory failure compared with nonpregnant patients with ALS [1]. Mechanical ventilation during pregnancy is an infrequent scenario [4]. This is, to our knowledge, the first report describing the use of long-term mechanical ventilation in a pregnant woman with ALS.

Case presentation

A 37-year-old woman, G3P2 with a 3-year history of ALS, was admitted to the emergency room with shortness of breath and tachypnea at 24 weeks of gestation. ALS had resulted in tetraplegia about a year prior to presentation. On admission, the patient had marked respiratory distress, with fast and shallow breaths using accessory muscles and a respiratory rate of 24 breaths per minute. Neurological examination showed marked dysarthria, muscular atrophy, and tetraplegia with hyperreflexia. Respiratory failure was diagnosed after the arterial blood gases showed acute hypoxemia and severe respiratory acidosis (Table 1); therefore, the patient was transferred to the intensive care unit (ICU), where emergency endotracheal intubation was performed. Ventilatory support was provided in a time-cycled, volume-limited mode with a Puritan Bennett™ 840 (Covidien, Mansfield, MA) ventilator and the patient was sedated with intravenous fentanyl as necessary. Community-acquired pneumonia was diagnosed on chest radiography and broad spectrum antibiotics were initiated (Figure 1). An early tracheostomy was performed 10 days after admission as the need for prolonged mechanical ventilatory support was identified. The ventilator parameters used during prolonged mechanical ventilation are displayed in Table 2. Based on the patient’s weight of 50 kg (body mass index [BMI], 18 kg/m²), enteral nutrition was initiated using a polymeric, hypercalcemic, low-protein, and low-carbohydrate formula to meet caloric demands without overloading the respiratory system. Requirements were calculated weekly and based on maternal and fetal requirements. Arterial blood gases were drawn daily during the acute illness and then weekly once she stabilized.

Figure 1

Chest X-ray on admission: right lower lobe infiltrate.

During prolonged mechanical ventilation, fetal monitoring was assessed using daily fetal heart rate tracings, weekly umbilical artery Doppler velocimetry, and a fetal growth scan every 2 weeks. Amniotic fluid index remained normal and there were no abnormalities in the umbilical artery Doppler. At 31 weeks of gestation, the estimated fetal weight was below the 3rd percentile, establishing the diagnosis of intrauterine growth restriction. Betamethasone was then administered to enhance fetal organ maturity.

The patient had a spontaneous preterm birth with vaginal delivery at 32 weeks of gestation (8 weeks after admission), without clinical or laboratory evidence of infection. The newborn was a female with a birth weight of 1190 g. The neonate was admitted to the neonatal ICU because of low birth weight but was discharged home a week later. The mother’s oxygenation and ventilatory status as well as neurologic status did not change significantly after delivery, and her overall postpartum course was uneventful. Due to the complex nature of end-of-life discussions regarding a new mother, those were initiated with the family while the patient was in the ICU, but no major decisions made at the time. The mother was discharged from the ICU one month postpartum and was transferred to a home care facility for continued mechanical ventilatory care.

Discussion

ALS is a neurodegenerative disease that rarely affects women of childbearing age [1, 3]. Despite limited data regarding the outcomes of ALS in pregnancy, the disease does not affect involuntary muscles such as the myocardium or myometrium. However, bulbar weakness and respiratory muscle dysfunction are well-known complications of the disorder. Diaphragmatic electromyography abnormalities are associated with lower forced vital capacity, lower arterial PO₂, and higher PCO₂ measurements. Hence, adaptations of the respiratory system to pregnancy are important in patients with neurodegenerative diseases [5]. These adaptations include an increase in upper airway resistance, increases in oxygen consumption by about 20%, increases in minute ventilation and tidal volume by 30%–50%, increases in the anteroposterior and transverse diameters of the chest wall, repositioning of the diaphragm, and decrease in the functional residual capacity [2].

Failure to increase tidal volume due to neuromuscular disease as required by pregnancy demands may lead to a compensatory increase in respiratory rate, which may eventually lead to respiratory muscle fatigue and respiratory failure. Due to this limited reserve, conditions that further reduce the reserve or increase metabolic rate or oxygen consumption such as pneumonia may also tip the balance and result in respiratory failure, as in this patient’s case. Studies assessing inspiratory and expiratory pressures of respiratory muscles show no significant change during normal pregnancy. However, due to an upward pressure on the diaphragm (the main inspiratory muscle) from the enlarging uterus, this muscle becomes more functional and efficient, but also more easily susceptible to fatigue [6]. In addition, although changes in the anteroposterior and transverse diameters of the chest wall are unlikely to affect respiratory muscle function in a normal pregnancy, the respiratory muscles of pregnant patients with ALS may be more sensitive to these changes with a potential for respiratory muscle fatigue and failure. In this patient, the acute event and decompensation were related to pneumonia; however, weaning difficulty was likely due to a combination of the underlying condition and pregnancy.

Evidence regarding mechanical ventilation during pregnancy is limited, and guidelines on best approach, goals of oxygenation, and ventilation are lacking. Physiological considerations must be taken into account while adjusting mechanical ventilation parameters during pregnancy. The fetus requires an oxygen gradient for continuous diffusion across the placenta; a partial pressure of carbon dioxide (PaCO₂) gradient of about 10 mm Hg between mother and fetus allows the fetus to offload CO₂ to the maternal circulation [2]. Therefore, experts recommend maintaining maternal O₂ saturation above 95% and a partial pressure of oxygen >75 mm Hg [4]. In the case reported herein, the PaCO₂ was maintained close to physiologic concentrations during pregnancy (Table 1). However, in conditions such as acute respiratory distress syndrome, lower tidal volumes and a higher PaCO₂ may be justifiable, since such ventilatory strategies are shown to reduce mortality in the nonpregnant population [3]. Because a fetal PaCO₂ of 65 mm Hg or above is associated with detrimental effects, it may be advisable to keep maternal PaCO₂ at 55 mm Hg or less.

Although ALS is not known to affect fetal outcomes [1], patients with more severe disease – as is the case with many chronic illnesses – may have fetal growth issues due to either chronic inflammatory state or, possibly, as in our patient’s situation, poor nutritional status. Our patient had a BMI below the lower limit of normal, even at mid-gestation, which suggests a poor nutritional status and/or muscle wasting due to immobility. Hence, the diagnosis of growth restriction is due to respiratory failure that lasted many weeks as well as a questionable nutritional status at baseline.

Delivery is not expected to result in an improvement of the underlying disease; therefore, induction of labor is unnecessary in these cases. The route of delivery in pregnant patients with neurodegenerative diseases is controversial [7, 8]; in the setting of respiratory failure, either vaginal or cesarean delivery may carry substantial risks. Therefore, obstetric indications for delivery in women with ALS do not have to be modified [8]. Loss of tone of the pelvic floor would probably facilitate a vaginal delivery, and abdominal surgery may lead to complications such as atelectasis and pneumonia, arguing against cesarean section [8].

Prolonged mechanical ventilation also entails significant ethical and management considerations in pregnant women. The decision must balance the increased risk of lower respiratory infections, further muscle wasting, nutritional status and metabolic requirements, and the quality of life that therapy can offer. End-of-life decisions are obviously very difficult to make in pregnant patients with a viable fetus and may understandably be postponed until delivery.

Conclusion

Pregnancy in patients with ALS can be complicated by a state of chronic respiratory failure and the need for mechanical ventilation. Long-term mechanical ventilation and vaginal delivery can be successfully performed in pregnancy, but goals of oxygenation and ventilation need to be modified and customized based on the underlying condition and the status of the mother.