Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

BACKGROUND: The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. METHODS: A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 µg/ml) or neostigmine (2, 4, or 8 µg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. RESULTS: Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 µg/ml neostigmine groups, respectively (P = 0.55). CONCLUSIONS: The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 µg/ml neostigmine or epidural bupivacaine with 2 µg/ml fentanyl.

A Randomized Controlled Trial Comparing Two Multimodal Analgesic Techniques in Patients Predicted to Have Severe Pain After Cesarean Delivery.

BACKGROUND: Improved pain control after cesarean delivery remains a challenging objective. Poorly treated acute pain following delivery is associated with an increased risk of chronic pain and depression. This study was conducted to determine whether the addition of systemic acetaminophen and an increased dose of intrathecal morphine would further reduce acute pain. The primary outcome was pain intensity with movement at 24 hours postoperatively. Secondary measures included persistent pain and depression at 8 weeks. METHODS: Seventy-four parturients scheduled for elective cesarean delivery under spinal anesthesia that were predicted to be above the 80th percentile for evoked pain intensity based on a 3-item preoperative screening questionnaire were enrolled. Patients in the intervention group received 300 mcg spinal morphine and 1 gram acetaminophen every 6 hours for 24 hours postoperatively. Patients in the control group received 150 mcg spinal morphine and placebo tablets. All patients received scheduled ibuprofen by mouth and IV morphine patient-controlled analgesia. At 24 hours, patients rated their pain intensity with movement, at rest, on average, and worst score using a visual analog scale for pain (100-mm unmarked line). The presence of persistent pain and depression was assessed at 8 weeks using the Edinburgh postpartum depression survey. RESULTS: Providing a higher dose of spinal morphine combined with systemic acetaminophen to patients predicted to be at high risk for severe post-cesarean delivery pain significantly reduced evoked pain scores with movement at 24 hours (mean ± SD: 46 ± 25 mm in control group versus 31 ±17 mm in intervention group, P = 0.009; 95% confidence interval for the difference between means: 4 mm, 26 mm). There was no difference in the incidence of persistent pain (13% (4/30) in control group versus 10% (3/30) in intervention group, P > 0.99), or depression at 8 weeks postoperatively (10% (3/30) in control group versus 13% (4/30) in intervention group, P > 0.99). CONCLUSIONS: Adding a higher dose of intrathecal morphine and oral acetaminophen to a multimodal pain regimen in patients predicted to be at risk for high acute postpartum pain after cesarean delivery results in a significant reduction of acute postoperative pain scores at 24 hours.

Labor prior to cesarean delivery associated with higher post-discharge opioid consumption.

BACKGROUND: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake. METHODS: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed. RESULTS: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups. CONCLUSION: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD.

Recovery of physical activity after cesarean delivery and its relationship with pain.

Pain and physical activity are tightly intertwined. Although their relationship has been explored in chronic pain conditions, we know little about the pattern of recovery in activity and its short- and long-term relationship with pain after surgery. We recruited 103 women undergoing elective cesarean delivery and acquired daily pain assessments and hourly steps in 98 of them for 2 months after surgery. Compliance was good, with 78% of subjects missing less than 7 days of activity. Study personnel required daily checking for compliance and 20 minutes per subject per week in study. Activity increased over the first 2 postoperative months in a log(time) manner. The slope of each modeled individual curve for activity was inversely correlated (r = -0.54; P < 0.0001) with worst daily pain. After removing these 2-month trends, pain and activity within an individual day were negatively associated with each point increase in pain being inversely associated with -119 steps (95% confidence interval [CI] = -214 to -25; P = 0.013). A patient's previous experience of pain was not associated with current activity as well as current activity was not associated with future pain scores. These data, although limited by the study of a single operation in a unique social circumstance with low risk of chronic postsurgical pain, demonstrate feasibility of measuring hourly activity for 2 months after surgery. Recovery from pain and inactivity are tightly correlated, and the negative relationship between within-day pain and activity without interday carryover relationships is in stark contrast to findings in chronic pain conditions.

Patterns of recovery from pain after cesarean delivery.

We know very little about the change in pain in the first 2 months after surgery. To address this gap, we studied 530 women scheduled for elective cesarean delivery who completed daily pain diaries for 2 months after surgery through text messaging. Over 82% of subjects missed fewer than 10 diary entries and were included in the analysis. Completers were more likely to be Caucasian, nonsmokers, and with fewer previous pregnancies than noncompleters. Daily worst pain intensity ratings for the previous 24 hours were fit to a log(time) function and allowed to change to a different function up to 3 times according to a Bayesian criterion. All women had at least one change point, occurring 22 ± 9 days postoperatively, and 81% of women had only one change, most commonly to a linear function at 0 pain. Approximately 9% of women were predicted to have pain 2 months after surgery, similar to previous observations. Cluster analysis revealed 6 trajectories of recovery from pain. Predictors of cluster membership included severity of acute pain, perceived stress, surgical factors, and smoking status. These data demonstrate feasibility but considerable challenges to this approach to data acquisition. The form of the initial process of recovery from pain is common to all women, with divergence of patterns at 2 to 4 weeks after cesarean delivery. The change-point model accurately predicts recovery from pain; its parameters can be used to assess predictors of speed of recovery; and it may be useful for future observational, forecasting, and interventional trials.

Day-to-day experience in resolution of pain after surgery.

We know little about the individual pain experience of patients recovering from surgery in the first weeks after hospital discharge. Here, we examine individual differences in the day-to-day experience after 2 major surgeries: lower limb total major joint arthroplasty (TJA) and cesarean delivery (CD). Fifty-five TJA patients and 157 CD patients were recruited to complete questionnaires and record their daily pain experiences after surgery. After hospital discharge, patients recorded their pain intensity once daily for 60 days (CD) or twice daily for 2 weeks, once daily for 2 weeks, weekly for 8 weeks, and monthly for 3 months (TJA). Pain scores were modeled using growth curve and Bayesian change-point models. Individual differences in the model fits were examined for evidence of day-to-day differences in pain. A log time model was the simplest model that fit the data, but examination of the residuals revealed high autocorrelation representing misspecification. A change-point model fit the data better and revealed that the form of recovery fundamentally changed between days 10 and 21 after surgery. These data add meaningfully to our understanding of recovery from pain after surgery by extending the period of frequent observations a few days after surgery to a 2-month period. These high time resolution data suggest that there is a typical experience of pain resolution after surgery, but that meaningful subpopulations of experience may exist. They also indicate that a transition occurs within 1 month after surgery from 1 pattern of change in pain over time to another.

Patterns of Opioid Prescription and Use After Cesarean Delivery.

OBJECTIVE: To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery. METHODS: We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home. RESULTS: A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range 30-40), the median number consumed was 20 (interquartile range 8-30), and leftover was 15 (interquartile range 3-26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription. CONCLUSION: The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.