Oral Presentation Society of Obstetric Medicine of Australia and New Zealand ASM 2023

Risk of developing hypertension following postpartum non-steroidal anti-inflammatory drug use: findings from a systematic review and meta-analysis (#25)

Arunima Jain 1 , Lauren Heath 1 , David H Tian 2 3 , Sai Siritharan 1 , Florensia Natali 4 , Mudith Jayasekara 1 , Lauren Thurgate 5 , Sean KM Seeho 6 , Anthony Delaney 4 5 7 , Amanda J Mather 1
  1. Department of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Department of Anaesthesia and Perioperative Medicine, Westmead Hospital, Sydney, NSW , Australia
  3. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia
  4. University of Sydney, Sydney, NSW , Australia
  5. Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
  6. Women and Babies Research, Faculty of Medicine and Health, Kolling Institute, Sydney, NSW, Australia
  7. Monash University, Melbourne, VIC, Australia

Background: Effective pain management plays a crucial role in optimising recovery after birth.1 Minimising opioid use is preferable given risks of nausea, constipation, sedation and opioid dependence.2 Non-steroidal anti-inflammatory drugs (NSAIDs) are effective and commonly used, but can potentially exacerbate hypertension as evidenced in pooled analyses of non-pregnant hypertensive patients and case reports during pregnancy.3-5 Therefore, guidelines suggest avoiding NSAIDs in women with hypertensive disorders of pregnancy (HDP) where possible, although adverse events have not been consistently reported in randomised controlled trials (RCTs).5-12

Aims: To review the incidence of hypertension and related adverse events following postpartum NSAID use in RCTs.

Methods: A systematic review of eight databases and four clinical trial registries after the year 2000 was performed in July 2020, as detailed in the PROSPERO protocol (CRD42020196054). RCTs which assessed safety and/or efficacy of NSAID use in postpartum women were included, not limited to those with HDP.

Results: The search revealed 12,173 records. Nine studies reported hypertension outcomes with the inclusion of 871 women (median 78, interquartile range 61-100), of which 610 had caesarean and 261 vaginal births.10,13-20 Follow-up duration was 24 hours in four studies, and three to 42 days in the remainder. Four of the nine studies included patients with HDP. Study design was heterogenous utilising variable inclusion criteria, NSAIDs (ibuprofen, valdecoxib, diclofenac, celecoxib) and comparators (placebo, herbal, paracetamol, opioid).

There was no standard method of reporting hypertension outcomes with parameters including: incidence of maternal hypertension (1 RCT), postpartum mean arterial pressure (3 RCTs), mean systolic blood pressure or BP (2 RCTs), severe hypertension (3 RCTs), need for postpartum antihypertensives (3 RCTs), mean postpartum stay (2 RCTs) or hospital readmission up to six weeks (2 RCTs). 10,13,14,16-18 The RCT which reported incidence of maternal hypertension in women with ‘severe preeclampsia’ found that a greater proportion of women within the NSAID group (36/57; 63%) experienced hypertension (BP ≥150/100mmHg) compared to those in the paracetamol group (16/56; 29%), with no difference in rates of severe hypertension (BP ≥160/110mmHg). 18

There were no differences in other hypertension outcomes reported by individual RCTs. Additionally, studies did not report data regarding incidence of eclampsia, hypertension at or beyond three months postpartum, acute kidney injury or cardiovascular events.

Conclusions: Our systematic review summarises the limited and heterogeneous data regarding risks of developing hypertension with postpartum NSAID use. Further RCTs with standardised outcome measures and longer follow-up duration will help inform clinical decision-making.

  1. Bellos I, Pergialiotis V, Antsaklis A, Loutradis D, Daskalakis G. Safety of non-steroidal anti-inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2020;56(3):329-339.
  2. Ullman R SL, Burns E, Mori R, Dowswell T. Parenteral opioids for maternal pain relief in labour. Cochrane Database Syst Rev. 2010;(9):CD007396.
  3. Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med. 1993;153(4):477-84.
  4. Makris A, Thornton C, Hennessy A. Postpartum hypertension and nonsteroidal analgesia. Am J Obstet Gynecol. 2004;190(2):577-578.
  5. Wasden SW, Ragsdale ES, Chasen ST, Skupski DW. Impact of non-steroidal anti-inflammatory drugs on hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014;4(4):259-263.
  6. Brown MA, Magee LA, Kenny LC, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24-43.
  7. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.
  8. Lowe SA BL, Lust K, McMahon LP, Morton MR, North RA, Paech MJ, Said JM. Guideline for the management of hypertensive disorders of pregnancy. Society of Obstetric Medicine of Australia and New Zealand, 2014. http://somanz.org/content/uploads/2020/07/HTguidelineupdatedJune2015.pdf
  9. Campbell L, Anastasio HB, Buermeyer A, et al. Avoiding NSAIDs postpartum for hypertensive disorders: A premature decision? Am J Obstet Gynecol. 2018;218(1 Supplement 1):S50.
  10. Blue NR, Drake-Lavelle S, Weinberg D, et al. Effect of ibuprofen versus acetaminophen on postpartum hypertension in preeclampsia with severe features: A double-masked, randomized controlled trial. Am J of Obstet Gynecol. 2018;218(1 Supplement 1):S604.
  11. Anastasio HB, Campbell LE, Buermeyer A, et al. Nonsteroidal antiinflammatory drug administration and postpartum blood pressure in women with hypertensive disorders of pregnancy. Obstet Gynecol. 2018;132(6):1471-1476.
  12. Viteri OA, England JA, Alrais MA, et al. Association of nonsteroidal antiinflammatory drugs and postpartum hypertension in women with preeclampsia with severe features. Obstet and Gynecol. 2017;130(4):830-835.
  13. Carvalho B, Chu L, Fuller A, Cohen SE, Riley ET. Valdecoxib for postoperative pain management after cesarean section: A randomized, double-blinded, placebo-controlled study. Anesth Analg. 2006;103(3):664-670.
  14. Matsota P, Nakou M, Kalimeris K, Batistaki C, Pandazi A, Kostopanagiotou G. A single dose of celecoxib 200 mg improves postoperative analgesia provided via patient-controlled epidural technique after caesarean section. Arch Med Sci. 2013;9(5):877-882.
  15. Munishankar B, Fettes P, Moore C, McLeod GA. A double-blind randomised controlled trial of paracetamol, diclofenac or the combination for pain relief after caesarean section. Int J Obstet Anesth. 2008;17(1):9-14.
  16. Penfield CA, McNulty JA, Oakes MC, Nageotte MP. Ibuprofen and postpartum blood pressure in women with hypertensive disorders of pregnancy: A randomized controlled trial. Obstet Gynecol. 2019;134(6):1219-1226.
  17. Triebwasser JE, Hesson A, Langen ES. A randomized-controlled trial to assess the effect of ibuprofen on postpartum blood pressure in women with hypertensive disorders of pregnancy. Pregnancy Hypertens. 2019;18:117-121.
  18. Vigil-De Gracia P, Solis V, Ortega N. Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: Randomized clinical study. J Matern Fetal Neonatal Med. 2017;30(11):1279-1282.
  19. Pour S, Hakimi S, Delazar A, Zadeh YJ, Mallah F. Eremostachys laciniata as effective as rectal diclofenac suppository in caesarean section pain relief: A triple blind controlled clinical trial. J Endometr Pelvic Pain Disord. 2020;12(1):26-34.
  20. Makris A, Thornton C, Tooher J, et al. 298 Effect of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure in the post-partum period: A randomised controlled trial. Pregnancy Hypertension. 2018;13:S40-S41.