A retrospective cohort study was performed in patients cared for at the University of Washington Obstetric Hypertension Clinic.
The authors have highlighted the following aims:
· To describe the pharmacodynamics of clonidine in pregnancy with particular attention to differences in individual hemodynamic responses.
· To determine whether differences in individual hemodynamic responses had an impact on fetal growth and birth weight.
· Finally to determine whether the pattern of hemodynamic response could be predicted by maternal characteristics or by baseline hemodynamic parameters that could be ascertained without noninvasive measurement of CO.
Charts were reviewed from 1997 to 2007 to identify subjects started on clonidine monotherapy after 16 weeks gestational age.
Results: Seventy-two women were identified who had been treated with clonidine monotherapy. One was excluded for acute pre-eclampsia.
Hemodynamic response to clonidine: Normative data from 89 nulliparous women who developed neither gestational hypertension nor pre-eclampsia are included for comparison. With all data combined, a decrease in MAP was associated with a decrease in TPR and a modest rise in CO.
The ↓CO Group experienced a substantial reduction in heart rate (HR) with an associated reduction in CO and a very modest change in TPR. Pretreatment hemodynamic profile (e.g., MAP, CO, HR, stroke volume, TPR), did not predict response as demonstrated by the similar starting point of each response vector.
Many women delivered prior to term, and the cohort experienced a high rate of pre-eclampsia. Mean birth weight percentile was lower in the ↓CO Group (26.1), compared to the ↓TPR Group (43.6), P = 0.02.
The ↓CO Group was less likely to be associated with a higher birth weight compared to the ↓TPR Group (relative risk ratio 0.81; 95% confidence interval 0.66–0.98) for an increase in birth weight by 100 g. The Mixed Group exhibited a trend toward a lower birth weight baby relative to the ↓TPR Group (relative risk ratio 0.83; 95% confidence interval 0.64–1.07). Women whose response was characterized by a reduction in CO delivered infants with a lower birth rate percentile and an increased incidence of birth weight <10th percentile.
In the study, Clonidine was found to have heterogeneous hemodynamic effects when used to treat hypertension in pregnancy. Fifty two percentage of patients experienced a primary reduction in vascular resistance.
In this report, women treated with clonidine experienced a heterogeneous response. Women in the ↓CO Group delivered babies with a lower birth weight percentile (26.1 vs. 43.6, P = 0.02) compared to the ↓TPR Group. The differential effect on fetal growth may be attributable to the differential hemodynamic effects of the drug. Alternatively, unknown factors intrinsically associated with the different responses could be responsible for the observed effect on growth.
A higher dose of clonidine occurred more commonly in the ↓CO Group. A higher maternal plasma clonidine concentration could be a determinant of the type of response group. But, there were no serum clonidine levels in this cohort to evaluate this hypothesis.
The heterogeneous response to treatment with clonidine seems to be associated with an impact on fetal growth. Similar fetal growth findings with clonidine that has a different mechanism of action than atenolol, suggest that the effect is due to the common effect on maternal hemodynamics.
As might be expected, a reduction in HR characterized the ↓CO Group with 20/22 women (91%) having a change in HR <0. All babies in this group with birth weights <10th percentile were delivered to women with a reduction in HR. In the entire cohort, a ΔHR <0 identified 12/14 babies born at <10th percentile. However, 41/64 women (64%) of the entire cohort had a ΔHR <0. While a decrease in HR was sensitive in predicting response group and small babies, it was not very specific.
Recommendations: First, by limiting the dose of clonidine to 0.15 mg/day and adding a second agent such as hydralazine when an additional reduction in BP is needed, the chance of a ↓CO effect will be reduced.
Second, if a decrease in HR is observed with clonidine, addition of a vasodilator such as hydralazine should again be considered. While this strategy would again decrease the chance of a ↓CO response, 33% of women whose treatment was altered might not have needed an additional agent to avoid a ↓CO response. If BP was not excessively reduced, this strategy would not be likely to have adverse effects.
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