The Effect of Magnesium Sulfate Loading Dose

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ajog.

org Poster Session IV

1174 Pharmacokinetics and Pharmacodynamics of


Aspirin in Pregnancy
Rupsa C. Boelig1, Edwin Lam2, Ankit Rochani3,
Gagan Kaushal3, Walter Kraft4
1
Thomas Jefferson University Hospital, Philadelphia, PA, 2National Institutes
of Health, NIH, MD, 3Thomas Jefferson University College of Pharmacy,
Philadelphia, PA, 4Sidney Kimmel Medical College, Thomas Jefferson
University, Philadelphia, PA
OBJECTIVE: The pharmacokinetics (PK) of aspirin are described
through serum salicylic acid levels, while pharmacodynamics (PD)
can be assessed through platelet activity measures, such as Platelet
Function Assay (PFA-100) clotting time (seconds (s)). PFA-100 time
increases with aspirin mediated platelet inhibition. There is scant
literature on the PK/PD of aspirin in pregnancy. The objective of this
study is to define the pharmacokinetics and pharmacodynamics of
aspirin through gestation.
STUDY DESIGN: We measured aspirin PK/PD in singletons at high risk
for preeclampsia. Participants were given either enteric or non-
enteric coated 81mg aspirin. Salicylic acid concentration was
measured 0.5-6 hr after a dose in first and third trimesters. PFA-100 1175 The effect of magnesium sulfate loading dose
closure time was measured after 1-4 weeks of aspirin therapy, and
and body mass index in achieving therapeutic levels
again in the third trimester 28-32 weeks. PK parameters were
Madushka De Zoysa1, Melissa Westermann2,
calculated, included maximum concentration (Cmax), time to reach
Tyler Yang3, Judith H. Chung4
Cmax (Tmax), area under the curve (AUC), and clearance. 1
University of California, Irvine, Long Beach, CA, 2University of California,
RESULTS: Nine singletons received 81mg enteric coated (n¼3) and Irvine, San Diego, CA, 3University of California, Irvine, Orange, CA, 4UC
non-enteric coated (n¼6) aspirin in the first (n¼9) and third Irvine Health, Orange, CA
trimester (n¼2) (TABLE). Enteric coated aspirin had a later T-max OBJECTIVE: Due to the increased volume of distribution in obesity,
(FIGURE A). There was a significant variability in aspirin absorption many medications are weight-based including anticoagulation and
in the first trimester. There was a significant increase in PFA-100 prophylactic antibiotics for cesarean delivery. Intravenous magne-
clotting time from pre to post therapy (MD 31.3  14.2s, one-sided sium sulfate, used for the prevention of eclamptic seizures, fetal
p¼0.04) (FIGURE B). There may be a higher AUC (p¼0.16) and neuroprotection, and tocolysis is administered via a 4-6 g load fol-
higher PFA-100 response (p¼0.32) with non-enteric coated aspirin, lowed by a 2g/hr maintenance dose, but there are no specific rec-
although this did not reach statistical significance. ommendations for dosing as a function of body mass index (BMI).
CONCLUSION: There is significant inter-individual variability in The purpose of this study was to investigate the effect of magnesium
aspirin absorption and platelet response. Non-enteric coated aspirin loading dose on side effect profile and ability to achieve therapeutic
produces higher salicylic acid exposures e measured by AUC and levels, as a function of BMI.
Cmax- in the first trimester. Mean PFA-100 clotting time, a measure STUDY DESIGN: A retrospective cohort study was performed from 12/
of aspirin response, was lower than traditional threshold of efficacy 1/12-12/1/14 comparing women who received a 4-g vs. 6-g mag-
of 150 seconds, and may be impacted by aspirin formulation. nesium load for preeclampsia, preterm labor, or both. Side effects
Further study is necessary on individual factors impacting aspirin and serum levels, drawn 2 hours after the loading dose were
absorption and platelet response in pregnancy in order to optimize compared. Linear regression of BMI vs. magnesium level by loading
dosing for preeclampsia prevention. dose and logistic regression by BMI Class, with respect to achieving a
therapeutic level (4.8-8.4 mg/dL), were performed.
RESULTS: 762 women were included; 425 (55.8%) received a 4-g
load. There were no differences in side effects between groups, and
no one achieved supratherapeutic levels (data not shown). The
regression coefficient in the model comparing BMI and magnesium
level, as a function of loading dose (Figure 1), was statistically sig-
nificant t¼-5.93, p< 0.001). When adjusted for potential con-
founders (Table 1), women receiving a 4-g load, obese Class 1, 2, and
3 women were 53%, 88%, and 89% less likely to achieve a thera-
peutic level as compared to non-obese women. Among women
receiving a 6-g load, obese Class 1, 2, and 3 women were 53%, 81%,
and 75% less likely to achieve a therapeutic level as compared to
non-obese women.
CONCLUSION: A significant proportion of obese women do not ach-
ieve therapeutic magnesium sulfate levels after either a 4-g or 6-g
loading dose. Because there was no increased risk of side effects with
a 6-g load, and no one achieved supratherapeutic levels, loading
doses of at least 6-g should be considered in obese women.

Supplement to JANUARY 2022 American Journal of Obstetrics & Gynecology S745


Poster Session IV ajog.org

hypertensive pregnancies. Lack of data is responsible for conflicting


guidelines regarding the ideal time for PP follow up. Therefore, we
developed a maternal BP trajectory using accurately obtained BP
measurements in PP.
STUDY DESIGN: People who delivered at our academic medical center
and whose newborns were evaluated at our pediatric clinics were
included.This was a quality intervention investigation(January 2018-
December 2019).BP values were obtained PP in hospital at 24 hours,
48 hours and time of discharge.After discharge, BP were collected at
time of newborn visits: 2 days after discharge, 2 weeks and 2 months
of infant age; and at time of PP follow up in obstetrics clinic. BP was
collected by trained medical assistants.BP panel data was analyzed
and plotted using mixed-effects models with time expressed using
cubic splines separately for first 10 days(knots at day 2, 4, 7) and for
days 5 through 42(knots at day 7, 14, 28). We developed BP tra-
jectories within the first ten days PP and from 5 days to 42 days
PP.Data was analyzed based on the presence of hypertensive disor-
ders and based on race.
RESULTS: 501 people who had 1610 BP values were included.A sta-
tistically significant difference in systolic(SBP) and diastolic
BP(DBP) in normotensives vs hypertensives was noted in first 10
days postpartum.Importantly, the peak in both groups was at 6 days.
However when analyzed by race, black mothers in both subgroups
did not have a decrease in SBP after the peak (graph 1).Postpartum
BP reference ranges were also established from 5 days to 42 days
PP(graph 2).
CONCLUSION: We noted different BP trajectories in white and black
mothers. Peak BP value was at 6 days PP regardless of hypertensive
status or race. Since most cases of preeclampsia occur in normo-
tensives, our data suggests the first visit PP for all women occur at 6
days PP.

1176 The impact of hypertensive status and race


on the postpartum blood pressure trajectory
Farah H. Amro1, S. Shahrukh Hashmi2, Kim C. Smith3,
K. Mariah Sankey1, Nikitha A. Cherayil4,
Michelle Barratt3, Sean C. Blackwell1, Baha M. Sibai5
1
Department of Obstetrics, Gynecology and Reproductive Sciences
McGovern Medical School at The University of Texas Health Science Center
at Houston (UTHealth), Houston, TX, 2Department of Pediatrics, Pediatric
Research Center, The University of Texas Medical School at Houston,
Houston, TX, Houston, TX, 3Department of Pediatrics, The University of
Texas Medical School at Houston, Houston, TX, Houston, TX, 4University of
Texas Health Sciences Center McGovern Medical School, Houston, TX,
5
Department of Obstetrics, Gynecology and Reproductive Sciences
McGovern Medical School at The University of Texas Health Science Center
at Houston (UTHealth), Houston, TX
OBJECTIVE: Limited data exists regarding the trajectory of blood
pressure (BP) in the postpartum period (PP) for normotensive and

S746 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2022

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