Intrathecal Opioids for Pain Control after Cesarean Delivery: Determining the Optimal Dose


About this study

Both hydromorphone and morphine are administered as part of spinal anesthesia to help improve pain control after cesarean delivery. In this study, the investigators are going to determine the doses of each of those medicines that provides optimal pain control to women undergoing cesarean delivery while limiting side effects related to those medicines. The investigators hypothesize that the doses of hydromorphone and morphine that provide optimal pain control without significant side effects will be 100 micrograms and 150 micrograms, respectively. The investigators further hypothesize that at each respective optimal dose, side effects will be less in the hydromorphone group.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Women presenting for elective cesarean delivery with no major co-morbidities, including pregnancy induced co-morbidities (e.g. pre-eclampsia)
  • Singleton gestation at term (37-42 weeks)
  • Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion Criteria:

  • Current or historical evidence of clinically significant medical disease or condition
  • Any contraindication to the administration of a spinal technique for anesthesia
  • History of hypersensitivity or idiosyncratic reaction to opioid medications
  • Chronic pain syndrome or current regular opioid use
  • Evidence of anticipated fetal anomalies
  • Allergy or intolerance to Tylenol, ketorolac, ibuprofen, or oxycodone
  • BMI > 40

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Hans Sviggum, M.D.

Closed for enrollment

More information


  • To compare analgesia and opioid-related side effects of intrathecal morphine and intrathecal hydromorphone after elective Cesarean delivery. Read More on PubMed
  • Despite compelling evidence for the safety and efficacy of intrathecal hydromorphone, the use of this opioid intrathecally for the pain management of patients undergoing cesarean delivery has not been widely accepted. The purpose of this retrospective study was to compare the reported efficacy and safety of pain management in women who received intrathecal hydromorphone (100 microg) vs in women who received intrathecal fentanyl (25 microg) or a local anesthetic for their cesarean delivery. The author hypothesized that intrathecal hydromorphone because of its known pharmacodynamics would provide better postoperative analgesia within the first 24 hours after cesarean delivery. The results of this retrospective chart review confirmed the hypothesis that intrathecal hydromorphone possesses the appropriate pharmacodynamics to facilitate optimal pain relief in patients undergoing cesarean delivery. It provided a comparable onset of effective pain relief, as well as a significantly prolonged duration of pain relief (P < .001) compared with intrathecal fentanyl or local anesthetic. Traditionally, intrathecal morphine was the opioid of choice for prolonged pain management during cesarean deliveries in which spinal anesthesia was selected. However, intrathecal hydromorphone was shown to be an effective and possibly even better substitute. Further research on intrathecal hydromorphone is needed. Read More on PubMed
  • Currently, morphine and fentanyl are the most commonly used intrathecal opioids for the postoperative pain management of patients who underwent cesarean delivery. Unfortunately, the analgesic benefits of these 2 drugs tend to fall into different extremes based on lipid solubility. Intrathecal hydromorphone may provide more consistent analgesia because its lipid solubility falls between that of the other 2 opioids. A 22-year-old woman with a 39-week intrauterine pregnancy, gravida 2, para 1, came in for a scheduled second-time cesarean delivery. Her preoperative history included a morphine allergy discovered when administered intrathecally during her first cesarean delivery. Thus, in this case, preservative-free hydromorphone, 100 microg, was administered intrathecally as the opioid replacement for the spinal anesthetic. Intrathecal hydromorphone was found to have provided superior pain relief with fewer side effects in this patient, who received intrathecal morphine for the same surgery 2 years earlier. This case report supports an emerging hypothesis that intrathecal hydromorphone is not only safe but possibly more effective than other intrathecal opioids for pain management after cesarean delivery. The purpose of this case report is to encourage the development of more research regarding this use of intrathecal hydromorphone. Read More on PubMed
  • Intrathecal morphine is often used for postoperative analgesia after surgery. We performed a meta-analysis to obtain more detailed information on the frequency of side-effects in patients receiving intrathecal morphine in combination with spinal anaesthesia compared with placebo treated patients. We clustered the analysis to patients receiving placebo, less than morphine 0.3 mg (M < 0.3), or equal to or more than morphine 0.3 mg (M > or = 0.3) and calculated the risk ratios of morphine vs placebo. Twenty-eight studies investigating 46 morphine groups vs placebo were included. A total of 790 patients with intrathecal morphine and 524 patients who received placebo were analysed. Compared with placebo the lower dose of morphine resulted in an increase of nausea (RR 1.4, 95% CI 1.1-1.7), vomiting (RR 3.1, 95% CI 1.5-6.4) and pruritus (RR 1.8, 95% CI 1.4-2.2). The higher dose resulted in an increased risk ratio for pruritus (RR 5.0, 95% CI 2.9-8.6), but not nausea (RR 1.2, 95% CI 0.9-1.6) or vomiting (RR 1.3, 95% CI 0.9-1.9). Overall, intrathecal morphine did not increase respiratory depression. However, the higher dose of intrathecal morphine was associated with more episodes of respiratory depression (7/80) compared with the lower dose (2/247). Intrathecal morphine is associated with a mild increase in side-effects. With a dose < 0.3 mg we found there were no more episodes of respiratory depression than in placebo patients who received systemic opioid analgesia. Read More on PubMed
  • Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose-response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose-response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose-the target dose-associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies. Read More on PubMed
  • To determine the effect of intrathecal injection of morphine 0.2 mg on postoperative analgesia, activity and satisfaction after elective cesarean section. Read More on PubMed
  • This series investigated the quality of analgesia and the incidence and severity of side effects of intrathecal morphine for post-cesarean analgesia administered over a dose range of 0.0-0.5 mg. Read More on PubMed
  • Very small doses of intrathecal (i.t.) morphine (25-200 microg) have been used in an effort to provide effective postoperative pain relief while minimizing side effects after cesarean delivery. We performed a double-blinded study in 40 patients presenting for elective cesarean delivery in which i.t. morphine was administered along with oral hydrocodone/acetaminophen and other medications commonly administered after cesarean delivery. We administered i.t. morphine by up-down sequential allocation of doses. For the purposes of this study, adequate postoperative analgesia was defined as comfort not requiring i.v. morphine for 12 h after spinal anesthesia with bupivacaine, fentanyl, and morphine. In addition, a time and cost comparison was performed for study patients receiving intrathecal morphine compared with a historical group of patients receiving patient-controlled analgesia with i.v. morphine. We were unable to determine with meaningful precision a dose of i.t. morphine to provide analgesia in this context. However, very small doses of i.t. morphine combined with oral hydrocodone/acetaminophen and other medications commonly prescribed after cesarean delivery provided postoperative pain relief with no more time commitment than patient-controlled analgesia (148 +/- 61 vs 150 +/- 57 min) and with significantly less acquisition cost ($15.13 +/- $4.40 vs $34.64 +/- $15.55). Read More on PubMed
  • The efficacy of epidural hydromorphone alone or in combination with epinephrine for postoperative analgesia was evaluated in 30 healthy women who underwent cesarean delivery with epidural anesthesia. They were assigned randomly to receive either 1.5 mg hydromorphone alone (N = 15) or 1.5 mg hydromorphone with 1/200,000 epinephrine (N = 15). Duration of analgesia (mean +/- SD) was 24.3 +/- 9.4 hours after the epidural injection of hydromorphone plus epinephrine. This was significantly greater (p less than 0.01) than the duration of 18.2 +/- 5.9 hours after the same dose of plain hydromorphone. Analgesia was more rapid in onset and significantly better at the 0.5, 1, 3, and 12 hours postoperatively in the hydromorphone-epinephrine group. Side effects including pruritus (73%), nausea (20%), and vomiting (15%) were of similar frequency with and without epinephrine. Although mean venous PCO2 (PvCO2) levels three and six hours after the hydromorphone-epinephrine dose were elevated significantly over the pre-drug PvCO2 levels, no respiratory depression was detected by an apnea monitor to which all patients were connected. The addition of epinephrine to epidural hydromorphone hastened onset and prolonged the duration of analgesia after cesarean section. Read More on PubMed

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