Objective
Prostaglandin E 1 (PGE 1 ) is commonly used in obstetric practice for labor induction and cervical ripening and in treating postpartum hemorrhage; however, its use in pregnant asthmatic patients has not been studied to date. The package insert states there is an unknown causal side effect for dyspnea and bronchospasm. Other pharmacological publications have stated that bronchoconstriction may occur with the use of PGE 1 . The study objective was to examine peripartum pregnant asthmatic patients who received prostaglandin E 1.
Study Design
Every patient who was administered PGE 1 from January 2010 through December 2013 was prospectively recorded. The charts were retrospectively reviewed. Peripartum patients with asthma were identified and further analyzed for any evidence of an asthma exacerbation following administration of the drug.
Results
A total of 234 of 2629 patients (8.9%) who received PGE 1 were identified as having asthma. None of the patients had any evidence of an asthma exacerbation (0 of 234; 95% confidence interval, 0–0.017). Of the 234 patients, 104 (44%) had active asthma and were receiving daily medication, and the remaining 130 patients had a medical history of asthma for which they used an inhaler on an as-needed basis. A total of 98 patients (42%) received greater than 400 μg of total dose. A post hoc statistical assessment was performed, and the study was sufficiently powered to detect any clinically meaningful increase in asthma exacerbation with PGE 1 usage, if such a risk existed.
Conclusion
Based on the 95% confidence interval of these data, the maximum risk for an asthma exacerbation following the use of prostaglandin E 1 is less than 2%. Although all medications administered to asthmatic patients in the peripartum period should be carefully selected, this information supports the use of prostaglandin E 1 in obstetric patients with asthma, if clinically indicated.
Prostaglandin E 1 (PGE 1 ) or misoprostol is commonly used off label in obstetric practice for labor induction and cervical ripening and in treating postpartum hemorrhage. No study to date has been performed to evaluate the safety of this medication in pregnant patients with asthma. Misoprostol is a synthetic prostaglandin E 1 analog that is available in 100 μg and 200 μg tablets, and the package insert states there is an unknown causal side effect for dyspnea and bronchospasm.
Other pharmacological publications have stated that bronchoconstriction may occur with the use of PGE 1 . The American College of Obstetricians and Gynecologists Practice Bulletin on induction of labor advocates the efficacy of prostaglandin analogs for cervical ripening with labor induction but does not discuss the safety of PGE 1 for asthmatic patients. The American College of Obstetricians and Gynecologists Practice Bulletin on postpartum hemorrhage lists PGE 1 as one of the options for medical management but does not discuss any warnings or contraindications with its use.
Theoretically, PGE 1 acts as a bronchodilator, as evidenced in treating aspirin-induced asthma. Thus, the objective of this study was to examine peripartum asthmatic patients who received prostaglandin E 1 and evaluate for any complications related to the drug usage, with a primary focus on asthma exacerbation.
Materials and Methods
Every patient who was administered prostaglandin E 1 from January 2010 through December 2013 was prospectively recorded by the University of Tennessee Medical Center, Knoxville, pharmacy department. Misoprostol tablets were the prostaglandin E 1 used at the medical center. All of the medical records were then retrospectively reviewed to identify peripartum patients who received PGE 1 and had a diagnosis of asthma. The patients with asthma were further divided into those with active asthma currently receiving daily treatment and those with a history of asthma who would use an inhaler on an as-needed basis.
The charts of all patients were then examined for any evidence of a respiratory complaint or asthma exacerbation following the administration of the medication. The chart review involved an evaluation of all physician, nursing, and anesthesia notes; medication and pharmacy records; vital sign flowsheets; and laboratory records.
Asthma is not a static disease and asthma exacerbations are difficult to define. The American Thoracic Society/European Respiratory Society Statement on asthma control and exacerbations developed recommendations in 2009 for the definitions of asthma exacerbations for use in clinical practice and clinical trials. In simplified terms, severe exacerbations are defined as “events that require urgent action on the part of the patient and physician to prevent a serious outcome” with the “use of systemic corticosteroids for at least 3 days.” Moderate exacerbations are defined as “events that are troublesome to the patient and that prompt a need for a change in treatment but that are not severe.”
These events should include one or more of the following: “a deterioration in symptoms, deterioration in lung function, and/or increased rescue bronchodilator use.” Mild exacerbations were not defined and specific changes in pulmonary function studies were not recommended. Therefore, an asthma exacerbation for this study was defined using these definitions. The indication for use, the route of drug administration, and the amount of PGE 1 administered to each patient was also recorded. Upon study completion, a post hoc power analysis was performed. The study was reviewed and approved by the University of Tennessee Medical Center Institutional Review Board.
Results
During the 4 year study period, 2629 patients received PGE 1 . Of these, a total of 234 (8.9%) were identified as peripartum pregnant patients with asthma. Of the 234 patients, 104 (44%) had active asthma and were receiving daily medication, and the remaining 130 patients had a history of asthma for which they used an inhaler on an as-needed basis.
The demographics of the study population are seen in Table 1 . None of the patients developed any clinical evidence of an asthma exacerbation as defined (0 of 234; 95% confidence interval, 0‒0.017) following the administration of prostaglandin E 1 . There were no reports of any deterioration in symptoms, and none of the patients required systemic corticosteroids or an increase in rescue bronchodilator use.
| Variable | Active asthma | History of asthma | Significance, P value |
|---|---|---|---|
| Number | 104 | 130 | |
| Maternal age, y | 27.3 ± 5.4 | 26.2 ± 5.8 | .41 |
| White, n (%) | 90 (86.5) | 109 (84) | .70 |
| African American, n (%) | 11 (10.5) | 16 (12) | .84 |
| Hispanic and other, n (%) | 3 (3) | 5 (4) | .49 |
| Mean gravidity | 2.13 ± 1.04 | 2.36 ± 1.57 | .69 |
| BMI >30 kg/m 2 , n (%) | 51 (49) | 72 (55) | .40 |
| BMI <30 kg/m 2 , n (%) | 53 (51) | 58 (45) | .40 |
| Multiple gestation | 6 | 5 | .70 |
| Cigarette smoker, n (%) | 44 (42) | 69 (53) | .13 |
The total amount of PGE 1 received by each patient ranged from a low of 25 μg to a high of 4200 μg. A total of 98 patients (42%) received greater than 400 μg of total dose. The route of administration was primarily intravaginal in 163 patients, followed by rectally in 73, and sublingual in 49. There were 51 patients who received PGE 1 by 2 different routes, usually rectal and sublingual for treating uterine atony/postpartum hemorrhage.
The indications for use were mostly cervical ripening/induction of labor in 135, followed by 88 cases of uterine atony/postpartum hemorrhage, and 25 patients with cervical preparation prior to a dilation and evacuation of an intrauterine fetal demise or fetus with lethal anomalies. Fourteen patients received PGE 1 for 2 indications of cervical ripening/induction of labor as well as uterine atony/postpartum hemorrhage. Table 2 depicts the breakdown of prostaglandin E 1 usage based on active asthma and history of asthma.
