Executive Summary

New research looks at the use of ketorolac, an injectable drug often used in the postoperative setting, as a possible option for easing pain prior to intrauterine device (IUD) insertion.

• While the American College of Obstetricians and Gynecologists recommends taking over-the-counter pain medication prior to IUD insertion, no specific drug is recommended.
• While ketorolac doesn’t reduce pain with IUD placement, it does reduce pain at five and 15 minutes after placement, researchers note. However, use of the drug calls for a potentially painful intramuscular injection and an in-clinic 30-minute wait time.

While the American College of Obstetricians and Gynecologists recommends taking over-the-counter pain medication prior to intrauterine device (IUD) insertion, no specific drug is recommended.¹ Research has just been published that looks at the use of ketorolac, an injectable drug often used in the postoperative setting.²

To evaluate the use of intramuscular injection of ketorolac compared with placebo saline injection for pain control with IUD placement, researchers conducted a randomized, double-blind, placebo-controlled trial between July 2012 and March 2014. Patients received 30 mg ketorolac or placebo saline intramuscular injection 30 minutes before IUD placement. The primary outcome was pain with IUD placement on a 10-cm visual analog scale. Sample size was calculated to provide 80% power to show a 2.0-cm difference (p=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at five and 15 minutes after IUD placement. Sixty-seven women participated in the study; 33 were placed in the ketorolac arm, and 34 were placed in the placebo arm. There were no differences in baseline demographics including age, body mass index, and race.

In the data analysis, there were no differences in median pain scores for IUD placement in the placebo compared with ketorolac groups (5.2 compared with 3.6 cm, p=.99). While there was a decrease in median pain scores at five minutes (2.2 compared with 0.3 cm, p?.001) and 15 minutes (1.6 compared with 0.1 cm, p?.001) after IUD placement, no difference was noted for all other time points. Nulliparous participants (n=16, eight per arm) had a decrease in pain scores with IUD placement (8.1 compared with 5.4 cm, p=.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement.¹ While ketorolac did not reduce pain with IUD placement, it did reduce pain at five and 15 minutes after placement, the researchers conclude.

“The demonstrated efficacy of ketorolac in this study is encouraging,” the scientists note. “However, it is limited by the need for a potentially painful intramuscular injection and an in-clinic 30-minute wait time.”

Is injection worth it?

As the study authors point out, the maximum analgesia provided by ketorolac occurs 1-2 hours post-injection, notes Andrew Kaunitz, MD, University of Florida Research Foundation professor and associate chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine – Jacksonville. This observation might explain why pain reduction was noted only after the procedure, he points out. While ketorolac is not expensive, logistical considerations might make routine use of pre-IUD placement injectable analgesia unrealistic in many ambulatory settings, says Kaunitz.

Prior studies suggest that pre-placement oral nonsteroidal anti-inflammatory drugs (NSAIDs) aren’t effective in reducing placement pain involving analgesic administration in the clinic less than one hour pre-IUD placement.³ Kaunitz agrees with the study authors that future trials of oral NSAID administration prior to arrival at the clinic are warranted.

What are the options?

A comparative study design against oral NSAIDs would be appropriate before ketorolac use is endorsed, says Anita Nelson, MD, professor in the Obstetrics and Gynecology Department at the David Geffen School of Medicine at the University of California in Los Angeles.

Studies that have looked at IUD insertions indicate that there is no treatment effective for general use for pain associated with device placement,^4-7 notes Nelson. Nelson presented information on contraception at the April 2014 Montana Family Planning Training in Helena.

Results from a 2011 study conducted to examine the effects of prophylactic misoprostol prior to intrauterine device placement in nulliparous women suggest the drug did not reduce patient perceived pain, but it did appear to increase preinsertion side effects,⁸ Nelson comments.

A 2013 literature review indicates that NSAIDs do reduce later cramping and bleeding associated with new Copper T380A IUD users,⁹ says Nelson.

REFERENCES

1. American College of Obstetricians and Gynecologists. Long-acting reversible contraception (LARC): IUD and implant. Accessed at http://bit.ly/1BtCEp8.
2. Ngo LL, War KK, Mody SK. Ketorolac for pain control with intrauterine device placement: A randomized controlled trial. Obstet Gynecol 2015; 126(1):29-36.
3. Allen RH, Bartz D, Grimes DA, et al. Interventions for pain with intrauterine device insertion. Cochrane Database Syst Rev 2009; doi: 10.1002/14651858.CD007373.pub2.
4. Hubacher D, Reyes V, Lillo S, et al. Pain from copper intrauterine device insertion: Randomized trial of prophylactic ibuprofen. Am J Obstet Gynecol 2006; 195(5):1272-1277.
5. Dijkhuizen K, Dekkers OM, Holleboom CA, et al. Vaginal misoprostol prior to insertion of an intrauterine device: An RCT. Hum Reprod 2011; 26(2):323-329.
6. Chor J, Bregand-White J, Golobof A, et al. Ibuprofen prophylaxis for levonorgestrel-releasing intrauterine system insertion: A randomized controlled trial. Contraception 2012; 85(6):558-562.
7. Allen RH, Raker C, Goyal V. Higher dose cervical 2% lidocaine gel for IUD insertion: A randomized controlled trial. Contraception 2013; 88(6):730-736.
8. Edelman AB, Schaefer E, Olson A, et al. Effects of prophylactic misoprostol administration prior to intrauterine device insertion in nulliparous women. Contraception 2011; 84(3):234-239.
9. Godfrey EM, Folger SG, Jeng G, et al. Treatment of bleeding irregularities in women with copper-containing IUDs: A systematic review. Contraception 2013; 87(5):549-566.