Publication date: Available online 2 March 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Nathan R. Blue, Cristina Murray-Krezan, Shana Drake-Lavelle, Daniel Weinberg, Bradley D. Holbrook, Vivek R. Katukuri, Lawrence Leeman, Ellen L. Mozurkewich Background Non-steroidal anti-inflammatory drug use has been shown to increase blood pressure in non-pregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. Objectives Our goal was to test the hypothesis that non-steroidal anti-inflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features. Study Design At delivery, we randomized women with preeclampsia with severe features to receive “around-the-clock” oral dosing with either 600mg of ibuprofen or 650mg of acetaminophen every six hours. Dosing began within six hours after delivery and continued until discharge, with opioid analgesics available as needed for breakthrough pain. Study drugs were encapsulated in identical capsules such that patients, nurses and physicians were masked to study allocation. Exclusion criteria were serum AST or ALT > 200mg/dL, serum creatinine >1.0mg/dL, infectious hepatitis, gastroesophageal reflux disease, age 〈 18 years, or current incarceration. Our primary outcome was the duration of severe-range hypertension, defined as the time (in hours, h) from delivery to the last blood pressure ≥ 160/110 mmHg. Secondary outcomes were time from delivery to last blood pressure ≥ 150/100 mmHg, mean arterial pressure (MAP), need for antihypertensive medication at discharge, prolongation of hospital stay for blood pressure control, postpartum use of short-acting antihypertensives for acute blood pressure control, and opioid use for breakthrough pain. We analyzed all outcome data according to intention-to-treat principles. Results We assessed 154 women for eligibility, of whom 100 met entry criteria, agreed to participate, and were randomized to receive postpartum ibuprofen or acetaminophen for first-line pain control. Seven patients crossed over or did not receive their allocated study drug, and 93 completed the study protocol in their assigned groups. We found no differences in baseline characteristics between groups, including mode of delivery, BMI, parity, race, chronic hypertension, and maximum blood pressure prior to delivery. We did not find a difference in the duration of severe-range hypertension in the ibuprofen versus acetaminophen groups (35.3h vs 38.0h, p=0.30). There were no differences between groups in the secondary outcome measures of time from delivery to last blood pressure ≥ 150/100 mmHg, postpartum MAP, maximum postpartum systolic or diastolic blood pressures, any postpartum BP ≥ 160/110 mmHg, short-acting antihypertensive use for acute blood pressure control, length of postpartum stay, need to extend postpartum stay for blood pressure control, antihypertensive use at discharge, or opioid use for inadequate pain control. In a subgroup analysis of patients who experienced severe-range hypertension, the mean time to blood pressure control in the acetaminophen group was 68.8h and ibuprofen group was 56.7h (p=0.26). At six weeks postpartum, there were no differences between groups in the rates of OB triage visits, hospital readmissions, continued opioid use, or continued antihypertensive use. Conclusion The first-line use of ibuprofen rather than acetaminophen for postpartum pain did not lengthen the duration of severe-range hypertension in women with preeclampsia with severe features.