PBLD7: Anesthetic Management of the Pregnant Patient with Cystic Fibrosis

Cystic fibrosis (CF) affects 1:1,600 to 1:2,500 live births and is the result of mutations on the long arm of chromosome 7 where the CF transmembrane conductance regulator protein resides. It is autosomal recessive and over 1,900 different mutations have been noted with ΔF508 the most common—70% of all cases. Ninety-five to ninety-eight percent of males with cystic fibrosis are infertile while female fertility is unaffected, although in severe disease there may be ovulation disturbances. Males need special intervention such as microepididymal sperm aspiration or testicular sperm aspiration followed by intracytoplasmic sperm injection. (1,2,3,4)

Absolute contraindications to pregnancy in CF include cor-pulmonale and severe pulmonary hypertension. Mortality in the modern era is still 20-30% in parturients with primary pulmonary hypertension. (1) FEV1 of less than 60% has been associated with increased pulmonary complications, (mainly pneumothorax, pulmonary exacerbations and preeclampsia), and an increased risk of mortality. Relative contraindications include: severe malnutrition (BMI < 18), ventilatory failure as shown by hypercapnia, and chronic exertional or nocturnal hypoxia. Burkholderia Cepacia carriers may be at risk of poor outcomes including worsening lung function, premature delivery, and mortality. This is especially true in those with existing poor lung function and colonization with B. Cepacia remains a relative contraindication to pregnancy. (1,3)

Patients with CF can have manifestations of the disease in multiple organ systems. Respiratory issues are most commonly associated with CF but problems can arise in the gastrointestinal, renal, psychiatric, orthopedic, issues with vascular access and within the endocrine system. Diabetes in CF generally results from an insulin deficient state although insulin resistance can become more prevalent during respiratory infections and pregnancy. Obstacles to proper diabetes care include: access to appropriate healthcare providers, surveillance, patient motivation and compliance to medication and diet instructions, and infections increasing stress. (1)

Approximately 25% of young adults with CF have diabetes. (1) Risk factors for developing diabetes among patients with CF include: advancing age, female gender and any pancreatic issues especially insufficiency. Those who develop DM are at an increased risk of developing more pulmonary complications, more severe pulmonary disease, a more inadequate nutritional status and liver disease. (1,3,8)

The care of a pregnant CF patient should include: an obstetric physician or maternal fetal medicine specialist, anesthesiologist, pulmonologist, an endocrinologist, a dietician and/or diabetes educators, social worker, access to a genetic counselor, psychologist, and neonatologist. (1) All patients should be screened for diabetes with an oral glucose tolerance test at 16-18 weeks and again at 28-30 if the initial test was negative. Gestational diabetes generally requires the use of diet modification and insulin with a target HbA1C of < 6.1%. Nutritional issues are important in CF as low BMI is associated with poor outcome and absorption of vitamins and nutrients may be impaired. CF patients with pancreatic insufficiency may have problems absorbing the fat-soluble vitamins A, D, E and K which may necessitate supplementation. Gastroesophageal reflux disease (GERD) is common in pregnancy and aspiration of acidic contents may worsen pulmonary status. Use of an H2 blocker or proton pump inhibitor may be necessary, as well as pro-kinetic agents. (1,4)

Anatomical changes coupled with hormonal changes have multiple effects on respiratory function during pregnancy. There is an increase in transverse diameter of the chest that offsets the enlarging uterus and elevated diaphragm. During pregnancy MV and VT increase while the ERV and FRC are decreased. (6) In one study of patients without CF, both the FVC and FVC% significantly increased after 14-16 weeks gestation. FVC% was noted to be higher in parous compared to primigravida women which suggests that changes in FVC during pregnancy persists postpartum. It was also noted that overweight individuals have a decrease in FVC and FEV1. (6)

Decreasing FVC and BMI are worrisome prognostic indicators. As noted above, FEV1 of less than 60% has been associated with increased pulmonary complications, (mainly pneumothorax, pulmonary exacerbations and preeclampsia), and an increased risk of mortality. Although FVC increases in healthy parturients, pregnant patients with CF typically exhibit a small yet statistically insignificant decrease in FVC and FEV1. (7) BMI of less than 18 is a relative contraindication to pregnancy and indicates a catabolic state whereby nutritional intake is insufficient for the demands of the woman and her developing fetus. (1,3)

The timing of delivery balances the risk of prematurity of the fetus with respiratory failure in the parturient. Discussions among team members with the patient will help facilitate this decision. Decreasing weight and worsening lung function are the primary impetus for expedited delivery. For vaginal delivery an early epidural placement is generally warranted to decrease the respiratory demands of labor. Avoidance of a high motor block and of thoracic sensory levels should be emphasized. Parenteral opioids are also best avoided due to depressing respiratory drive and blunting of the cough reflex. Ideally a dilute local anesthetic—either with or without opioids—titrated to a T10 sensory level should provide adequate analgesia. (2,5)

If cesarean section is warranted then avoidance of general endotracheal anesthesia is preferable unless an emergency exists. GETA can worsen lung function and predisposes the patient to bronchospasm, laryngospasm, and pneumothorax due to positive pressure in lieu of possible pulmonary blebs. Strategies to reduce complications from GETA include: humidification of inspired air, frequent suctioning of secretions, avoidance of nitrous oxide and ventilator settings that allow sufficient expiratory time to avoid air trapping and breath stacking. The goal of neuraxial anesthesia for C-section is balancing a high enough block (generally T6) while avoiding a high thoracic block that may impair motor input and the initiation of hyperventilation. Epidural or combined spinal epidural with low dosed spinal is preferred over the uncertainty of a regular spinal dose alone. (2,5) Invasive monitoring including arterial line, central venous access, and echocardiography may be necessary no matter the anesthetic chosen. A recent cohort study found that the 10-year survival of CF women who became pregnant was no worse compared to those who had not. (1) Additionally in one study, pregnancy in CF patients had no long-term effect on lung function from the pre-pregnancy state. The only significant predictors of decline in lung function were higher function at the beginning of the study and pancreatic insufficiency. (7)

Case Presentation continued:
Preoperatively you place a left radial arterial catheter and a second IV. Due to your concerns of her respiratory status you decide on a combined spinal-epidural technique. You administer hyperbaric bupvicaine 7.5% 1 mL mixed with fentanyl 15 mcg and preservative-free morphine 100 mcg intrathecally and the epidural catheter is threaded without difficulty. The patient develops a T6 sensory level and tolerates the cesarean section through delivery but develops significant pain upon exteriorization of the uterus. Your surgeon pauses as you cautiously dose up the epidural with chloroprocaine. This dose up is well tolerated. Her newborn has APGARS of 7 and 8 and is placed in the NICU. Due to the mother’s elevated white count and low-grade temperature the evening prior, the newborn is placed on a prophylactic dual antibiotic regimen. Both mother and baby have an uneventful course.

Final discussion:

Many patients with end-stage CF have undergone lung transplantation, and these patients may achieve pregnancy post-transplant. To date, there has not been a systematic review of allograft function after pregnancy. A recent case series of ten CF post lung transplant pregnancies resulted in nine live births and one therapeutic abortion. Five of the nine births were premature, three women developed organ rejection during pregnancy and four died within 38 months of delivery. (9) Therefore, it is necessary to stress the high risk present to the mother and fetus. Care of the post-lung transplant parturient is similar to those who have not been transplanted. Special attention is required to observe respiratory dysfunction developing from obliterative bronchiolitis, and allograft rejection. It is important to continue anti-rejection medication, and to monitor the extra-pulmonary manifestions of CF, especially diabetes. It is also imperative to control GERD in the post-lung transplant patient, as uncontrolled acid reflux and aspiration has been noted to contribute to allograft rejection. (3,4)

Finally, there has been some work using extracorporeal membrane oxygenation (ECMO) in patients with CF, and with that the question of its utility in a postpartum scenario has arisen. In general, its use should be reserved for situations where the primary etiology of respiratory failure is reversible, or where it is a bridge to definitive treatment (transplantation). (10,11) It is recommended that implementation be limited to individuals who are already listed for transplantation or in whom will be listed promptly. In one small study of 72 CF patients, 52% survived their ECMO run, but the number progressing to completed transplantation was not recorded. (11)

References:

1. James Geake, George Tay, Leonie Callway and Scott C. Bell (2014). Pregnancy and cystic fibrosis: Approach to contemporary management. Obstetric Medicine, 7(4) 147-155
2. M. Deighan, S. Ash, R. McMorrow (2013). Anaesthesia for parturients with severe cystic fibrosis: a case series. International Journal of Obstetric Anesthesia, 23(1) 75-79
3. Edmund M.T. Lau, Carmel Moriarty, Robert Ogle, Peter T. Bye (2010). Pregnancy and Cystic Fibrosis. Paediatric Respiratory Reviews, 11(2) 90-94
4. F.P. Edenborough et al. (2008) Guidelines for the management of pregnancy in women with cystic fibrosis. Journal of Cystic Fibrosis, 7 S2 – S32
5. Chestnut’s Obstetric Anesthesia: Principles and Practice, 5th edition, 2014, David H. Chestnut, et al.
6. G. Grindheim et al. Changes in pulmonary function during pregnancy: a longitudinal cohort study. BJOG 2012: 119:94-101
7. Monica Ahluwalia et al. Cystic fibrosis and pregnancy in the modern era: A case control study. Journal of Cystic Fibrosis, 13 January 2014, 69-73
8. BC Marshall et al. Epidemiology of Cystic Fibrosis Related Diabetes. J. Pediatrics: May; 146(5): 681-7
9. Khin Gyi et al. Pregnancy in cystic fibrosis lung transplant recipients: Case series and review. Journal of Cystic Fibrosis, 5 (2006) 171-175
10. Shelia Sivam, et al. Use of extracorporeal membrane oxygenation in cystic fibrosis in an Australian cystic fibrosis centre. Internal Medicine Journal, 48 (2018) 340-343
11. Don Hayes Jr, et al. Survival of patients with cystic fibrosis on ECMO: analysis of the Extracorporeal Life Support Organization Registry. Int J Clin Exp Med; 7(5): 1370-1372