Conference Coverage

Status asthmaticus risk upped fourfold with IV labetalol for preeclampsia

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Daniel Ouellette, MD, FCCP, comments on Asthma

I teach my residents and fellows the “rule of thirds”: One-third of asthma patients get worse during pregnancy; one-third get better; one-third stay the same.” Asthma during pregnancy remains a challenging problem, with physicians striving to treat two complicated patients (mother and child) safely and effectively. We learn now that the use of labetalol, a beta-blocker, to treat preeclampsia in pregnant asthma patients may be associated with an increased incidence of status asthmaticus. Until we learn more about these occurrences, we should use great caution in treating pregnant asthma patients with labetalol and other beta-blockers

Dr. Daniel R. Ouellette


 

REPORTING FROM THE PREGNANCY MEETING

– A maternal death occurred at Columbia University Medical Center after a patient with asthma was given intravenous labetalol, prompting a study that found an elevated risk of status asthmaticus associated with intravenous (IV) labetalol administration but not with the uterotonic carboprost.

“Overall, 71.4% of status asthmaticus cases occurred among women receiving IV labetalol,” said Whitney A. Booker, MD, speaking about the findings at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Dr. Whitney A. Booker Kari Oakes/Frontline Medical News

Dr. Whitney A. Booker

Dr. Booker and her colleagues used a national database to determine that the incidence of status asthmaticus in patients with asthma was almost four times higher when patients with preeclampsia were given IV labetalol: The rate was 6.5 per 1,000 patients given IV labetalol, compared with 1.7 per 1,000 for patients who received other antihypertensives.

The risk of status asthmaticus didn’t reach statistical significance when women with asthma who experienced postpartum hemorrhage were given carboprost, compared with other uterotonics (3.1 vs. 1.0 per 1,000 patients; P = .56).

“Some regularly used medications in obstetrics can trigger bronchospasm,” said Dr. Booker; the American College of Obstetricians and Gynecologists lists both carboprost and labetalol as contraindicated for use in patients with asthma because of the potential for bronchospasm with each medication.

However, she said, data on the actual risk of bronchospasm when these medications are used in obstetric patients is limited.

The retrospective cohort study constructed by Dr. Booker and her colleagues at Columbia University Medical Center’s department of obstetrics and gynecology tapped 10 years’ worth of data from a large inpatient drug utilization database.

Dr. Booker, a maternal-fetal medicine fellow, said that patients were included if they were admitted for delivery and had a diagnosis of preeclampsia or postpartum hemorrhage. Of the 5.7 million hospitalizations from 2006 to 2015, 2.5% were for postpartum hemorrhage, and 4.2% for preeclampsia.

Of the patients with hemorrhage, 5,633 had a prior history of asthma, as did 12,486 of the patients with preeclampsia. In both groups, a little more than a third of patients were younger than 25 years, and about a quarter were black. Half were on Medicaid, and most were in urban areas and cared for in a teaching hospital.

The first outcome that Dr. Booker and her colleagues looked at was how practice patterns for postpartum hemorrhage varied according to whether patients had asthma; to do so, they looked at receipt of carboprost, misoprostol, and methylergonovine. A similar analysis was performed for the second outcome addressing patients with preeclampsia, in which investigators examined the use of both IV and oral labetalol, hydralazine, and nifedipine. For this and the hemorrhage outcome, the investigators performed multivariable analysis, with receipt of carboprost and IV labetalol as the outcomes of interest.

Finally, the investigators assessed the risk of status asthmaticus by comparing receipt of either carboprost (for postpartum hemorrhage) or IV labetalol (for preeclampsia) with receipt of the other medications to treat these conditions.

They found that overall, 11.4% of patients with asthma and 18% of patients without asthma received carboprost to treat postpartum hemorrhage, which makes for an adjusted risk model of 0.68 (95% confidence interval, 0.62-0.74) for receipt of carboprost for patients with asthma versus those without.

However, the pattern was different for IV labetalol: 18.5% of patients with asthma and preeclampsia received labetalol, compared with 16.7% of those without asthma. After statistical adjustment, patients with asthma had a risk ratio of 0.93 (95% CI, 0.90-0.97) for receiving IV labetalol for preeclampsia.

The analysis showed that pregnant patients with asthma were less likely to be given carboprost than labetalol, although the actual risk of status asthmaticus was higher when patients with asthma received labetalol than when they received carboprost.

“Given similar theoretical risks, obstetric providers currently administer carboprost differently than labetalol. ... Obstetricians should proceed with caution prior to giving labetalol to patients with underlying asthma,” said Dr. Booker.

During the discussion after the presentation, one attendee suggested that a next step might be to examine claims databases in conjunction with the findings of Dr. Booker’s current work in order to see whether there’s an association between asthma medication prescription fills – a surrogate for disease severity – and the risk of bronchospasm. Dr. Booker agreed that this might be a promising line of inquiry.

Dr. Booker and her colleagues reported that they had no conflicts of interest. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Booker W et al. Am J Obstet Gynecol. 2018 Jan;218:S51.

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