Good intentions: the overprescription of opioids for analgesia with oocyte retrievals

Abstract

Today’s opioid crisis has been associated with the overprescribing of opiates and opioid derivatives by physicians, especially after surgical procedures. Although physicians prescribe medications such as hydrocodone and oxycodone in the immediate postoperative period with the good intention of controlling pain, these powerful medications can lead to chronic use and overdose (1Hah J.M. Bateman B.T. Ratliff J. Curtin C. Sun E. Chronic opioid use after surgery: implications for perioperative management in the face of the opioid epidemic.Anesth Analg. 2017; 125: 1733-1740Crossref PubMed Scopus (344) Google Scholar). Optimal pain control after various surgical procedures is an ongoing area of exploration. Currently, there is no well-accepted pain regimen after oocyte retrieval, and studies have focused mostly on sedation methods during the retrieval procedure itself (2Kwan I. Bhattacharya S. Knox F. McNeil A. Pain relief for women undergoing oocyte retrieval for assisted reproduction.Cochrane Database Syst Rev. 2013; 31CD004829Google Scholar). Many patients undergoing in vitro fertilization receive additional narcotic pain medications after oocyte retrieval, both during their postanesthesia recovery and as part of their home-going prescribed medications.In this month’s Fertility and Sterility, Sacha et al. (3Sacha C.R. Mortimer R. Hariton E. James K. Hosseini A. Gray M. et al.Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.Fertil Steril. 2022; 117: 133-141Abstract Full Text Full Text PDF Scopus (2) Google Scholar) are the first to compare the effects of intravenous (IV) acetaminophen with those of oral acetaminophen and a placebo on postoperative pain scores and time to discharge. The investigators randomized 161 women aged 18–43 years undergoing oocyte retrieval at an academic fertility center. The women were randomized to 1 of 3 groups: preoperative 1 g of IV acetaminophen and oral placebo; 1 g of oral acetaminophen and IV placebo; or both oral and IV placebo. The pain scores immediately after the procedure were measured using the postoperative visual analogue scale. The investigators then assessed the difference in preoperative and postoperative pain scores at different time intervals as the primary endpoint.In this study, it was found that there was no difference in the primary outcome of pain scores at 10 or 30 minutes after the procedure or at discharge. As a secondary outcome, an analysis of morphine milligram equivalents showed that the total opioid dose was the lowest in the group that received 1 g of IV acetaminophen, although this result was not statistically significant. No patient required opioids by postoperative day 2. Additionally, there was no difference in the time to discharge. Finally, there were no effects on oocyte maturity and the potential of oocytes or early pregnancy rates.Because there is considerable interest in reducing pain scores after retrieval without the use of narcotics, a major strength of this study is that it was the first to evaluate the use of IV acetaminophen in this setting. Another strength is that the investigators used a randomized design and controlled for demographic and clinical characteristics of the patients, their oocyte characteristics, and the number of oocytes received (3Sacha C.R. Mortimer R. Hariton E. James K. Hosseini A. Gray M. et al.Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.Fertil Steril. 2022; 117: 133-141Abstract Full Text Full Text PDF Scopus (2) Google Scholar). The design of the study with the 3 experimental groups is advantageous because it allows for the evaluation of a specific medication, its route of administration, and its effect on the pain scores.Although this study sheds light on an important question regarding optimal anesthesia regimens for postoperative pain with regard to oocyte retrieval, it is not without some limitations. The small sample size might have led to an underpowered study. In addition, variations in adjuncts or the pre-emptive use of opioids by the anesthesiologist might have prevented the ability to assess for true differences among the groups even in a randomized model. Further, these findings are not generalizable to oocyte retrievals that occur with the patient under local anesthesia alone, which is not uncommon in our field. The dose of the placebo or oral or IV acetaminophen was given at a variable rate of 30–60 minutes before the procedure. Although the investigators suggested that this was controlled for, differences in the time of administration could have altered the pain scores because of variations in the timing of peak effects of oral and IV acetaminophen. For example, the average duration reported for the procedure in each group was 13 minutes. The onset of the action of oral acetaminophen is within 1 hour and that for IV acetaminophen is within 10 minutes; the peak effects occur in 1 hour for oral doses (assuming that no delayed gastric emptying is present) and within 30 minutes for IV formulations (4Candido K.D. Perozo O.J. Knezevic N.N. Pharmacology of acetaminophen, nonsteroidal antiinflammatory drugs, and steroid medications: implications for anesthesia or unique associated risks.Anesthesiol Clin. 2017; 35: e145-e162Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). Presumably, the peak effect of this medication in the experimental groups might have worn off by the time of conclusion of the procedure, resulting in the finding of no difference in the postoperative pain scores. A confounding factor is that acetaminophen was given alongside monitored anesthesia care, during which the patients were already receiving opioids such as fentanyl. Furthermore, the investigators noted possible differences in the anesthesiologist’s use of pain adjuvants (e.g., lidocaine) as part of their regimens.This kind of research is an excellent first step in our explorations of alternate nonnarcotic regimens. Although this study might have been underpowered, preliminarily, it suggests that preoperative IV acetaminophen does not offer additional benefit to justify its high cost. Further studies are necessary to ultimately develop more consistent standards in our field. One suggested approach for additional study would be to evaluate the postoperative pain scores when 1 g of IV or oral acetaminophen is given as a first-line agent if/when the visual analogue scale scores qualify the patient for additional pain medications after the procedure. Additional areas of interest include the use of dexamethasone and/or lidocaine intraoperatively to further reduce postoperative opioid needs as well as the incorporation of the well-studied medications used in enhanced recovery after surgery pathways for gynecologic surgery, such as gabapentin or ketorolac (5Beverly A. Kaye A.D. Ljungqvist O. Urman R.D. Essential elements of multimodal analgesia in enhanced recovery after surgery (ERAS) guidelines.Anesthesiol Clin. 2017; 35: e115-e143Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). As with all surgical procedures, it is imperative in reproductive endocrinology and infertility practice that we develop multimodal reduced-narcotic pain control regimens for patients undergoing oocyte retrieval; in this way, we can do our part to lessen or eliminate the reliance on narcotics that currently remains rampant in the field of medicine. Today’s opioid crisis has been associated with the overprescribing of opiates and opioid derivatives by physicians, especially after surgical procedures. Although physicians prescribe medications such as hydrocodone and oxycodone in the immediate postoperative period with the good intention of controlling pain, these powerful medications can lead to chronic use and overdose (1Hah J.M. Bateman B.T. Ratliff J. Curtin C. Sun E. Chronic opioid use after surgery: implications for perioperative management in the face of the opioid epidemic.Anesth Analg. 2017; 125: 1733-1740Crossref PubMed Scopus (344) Google Scholar). Optimal pain control after various surgical procedures is an ongoing area of exploration. Currently, there is no well-accepted pain regimen after oocyte retrieval, and studies have focused mostly on sedation methods during the retrieval procedure itself (2Kwan I. Bhattacharya S. Knox F. McNeil A. Pain relief for women undergoing oocyte retrieval for assisted reproduction.Cochrane Database Syst Rev. 2013; 31CD004829Google Scholar). Many patients undergoing in vitro fertilization receive additional narcotic pain medications after oocyte retrieval, both during their postanesthesia recovery and as part of their home-going prescribed medications. In this month’s Fertility and Sterility, Sacha et al. (3Sacha C.R. Mortimer R. Hariton E. James K. Hosseini A. Gray M. et al.Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.Fertil Steril. 2022; 117: 133-141Abstract Full Text Full Text PDF Scopus (2) Google Scholar) are the first to compare the effects of intravenous (IV) acetaminophen with those of oral acetaminophen and a placebo on postoperative pain scores and time to discharge. The investigators randomized 161 women aged 18–43 years undergoing oocyte retrieval at an academic fertility center. The women were randomized to 1 of 3 groups: preoperative 1 g of IV acetaminophen and oral placebo; 1 g of oral acetaminophen and IV placebo; or both oral and IV placebo. The pain scores immediately after the procedure were measured using the postoperative visual analogue scale. The investigators then assessed the difference in preoperative and postoperative pain scores at different time intervals as the primary endpoint. In this study, it was found that there was no difference in the primary outcome of pain scores at 10 or 30 minutes after the procedure or at discharge. As a secondary outcome, an analysis of morphine milligram equivalents showed that the total opioid dose was the lowest in the group that received 1 g of IV acetaminophen, although this result was not statistically significant. No patient required opioids by postoperative day 2. Additionally, there was no difference in the time to discharge. Finally, there were no effects on oocyte maturity and the potential of oocytes or early pregnancy rates. Because there is considerable interest in reducing pain scores after retrieval without the use of narcotics, a major strength of this study is that it was the first to evaluate the use of IV acetaminophen in this setting. Another strength is that the investigators used a randomized design and controlled for demographic and clinical characteristics of the patients, their oocyte characteristics, and the number of oocytes received (3Sacha C.R. Mortimer R. Hariton E. James K. Hosseini A. Gray M. et al.Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.Fertil Steril. 2022; 117: 133-141Abstract Full Text Full Text PDF Scopus (2) Google Scholar). The design of the study with the 3 experimental groups is advantageous because it allows for the evaluation of a specific medication, its route of administration, and its effect on the pain scores. Although this study sheds light on an important question regarding optimal anesthesia regimens for postoperative pain with regard to oocyte retrieval, it is not without some limitations. The small sample size might have led to an underpowered study. In addition, variations in adjuncts or the pre-emptive use of opioids by the anesthesiologist might have prevented the ability to assess for true differences among the groups even in a randomized model. Further, these findings are not generalizable to oocyte retrievals that occur with the patient under local anesthesia alone, which is not uncommon in our field. The dose of the placebo or oral or IV acetaminophen was given at a variable rate of 30–60 minutes before the procedure. Although the investigators suggested that this was controlled for, differences in the time of administration could have altered the pain scores because of variations in the timing of peak effects of oral and IV acetaminophen. For example, the average duration reported for the procedure in each group was 13 minutes. The onset of the action of oral acetaminophen is within 1 hour and that for IV acetaminophen is within 10 minutes; the peak effects occur in 1 hour for oral doses (assuming that no delayed gastric emptying is present) and within 30 minutes for IV formulations (4Candido K.D. Perozo O.J. Knezevic N.N. Pharmacology of acetaminophen, nonsteroidal antiinflammatory drugs, and steroid medications: implications for anesthesia or unique associated risks.Anesthesiol Clin. 2017; 35: e145-e162Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). Presumably, the peak effect of this medication in the experimental groups might have worn off by the time of conclusion of the procedure, resulting in the finding of no difference in the postoperative pain scores. A confounding factor is that acetaminophen was given alongside monitored anesthesia care, during which the patients were already receiving opioids such as fentanyl. Furthermore, the investigators noted possible differences in the anesthesiologist’s use of pain adjuvants (e.g., lidocaine) as part of their regimens. This kind of research is an excellent first step in our explorations of alternate nonnarcotic regimens. Although this study might have been underpowered, preliminarily, it suggests that preoperative IV acetaminophen does not offer additional benefit to justify its high cost. Further studies are necessary to ultimately develop more consistent standards in our field. One suggested approach for additional study would be to evaluate the postoperative pain scores when 1 g of IV or oral acetaminophen is given as a first-line agent if/when the visual analogue scale scores qualify the patient for additional pain medications after the procedure. Additional areas of interest include the use of dexamethasone and/or lidocaine intraoperatively to further reduce postoperative opioid needs as well as the incorporation of the well-studied medications used in enhanced recovery after surgery pathways for gynecologic surgery, such as gabapentin or ketorolac (5Beverly A. Kaye A.D. Ljungqvist O. Urman R.D. Essential elements of multimodal analgesia in enhanced recovery after surgery (ERAS) guidelines.Anesthesiol Clin. 2017; 35: e115-e143Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). As with all surgical procedures, it is imperative in reproductive endocrinology and infertility practice that we develop multimodal reduced-narcotic pain control regimens for patients undergoing oocyte retrieval; in this way, we can do our part to lessen or eliminate the reliance on narcotics that currently remains rampant in the field of medicine. Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trialFertility and SterilityVol. 117Issue 1PreviewTo compare the effect of preoperative intravenous (IV) acetaminophen versus oral (PO) acetaminophen or placebo on postoperative pain scores and the time to discharge in women undergoing oocyte retrieval. Full-Text PDF