https://orcid.org/0000-0002-0063-5589
Abstract
Objective
Achieving functional recovery after cesarean delivery is critical to a parturient’s ability to care for herself and her newborn. Adequate pain control is vital, and without it, many other aspects of the recovery process may be delayed. Reducing opioid consumption without compromising analgesia is of paramount importance, and enhanced recovery pathways have generated considerable interest given their ability to facilitate this. Our group’s process for reducing opioid consumption for cesarean delivery patients evolved over time. We first demonstrated that providing additional incisional pain control with continuous bupivacaine infusions through wound catheters, with the concurrent use of neuraxial morphine, reduced postoperative opioid use. Iterations of an enhanced recovery after cesarean (ERAC) delivery pathway were then implemented after the Society for Obstetric Anesthesia and Perinatology’s consensus statement for ERAC was issued to eliminate variability in both hospital course and in the treatment of postoperative pain. In this retrospective cohort analysis, we sought to identify whether adding ERAC protocols to our existing combination of neuraxial morphine and wound soaker catheters further reduced opioid consumption after cesarean delivery.
Methods
A retrospective cohort analysis of cesarean deliveries from 2015 through 2020 was performed. Deliveries were divided by analgesic pathway into four time-periods – time-point 1 [January 2015-April 2016, previous standard of care (control, N = 61)]: neuraxial morphine in addition to as needed opioid and non-opioid analgesics; time-point 2 [May 2016–May 2019, introduction of wound soaker (wound-soaker, N = 40)]: continuous wound catheter infusions of local anesthetic, neuraxial morphine in addition to as needed opioid and non-opioid analgesics; time-point 3 [May 2019–December 2019, wound soaker + early ERAC pathway (early ERAC, N = 78)]: continuous wound catheter infusion of local anesthetic, neuraxial morphine, in addition to scheduled non-opioid analgesics (acetaminophen and ibuprofen) every 6 h, alternating in relation to one another so that one is given every 3 h; time-point 4 [January 2020–July 2020, wound soaker + late ERAC pathway (late ERAC, N = 57)]: continuous wound catheter infusion of local anesthetic, neuraxial morphine in addition to non-opioid analgesics scheduled together every 6 h (to facilitate periods of uninterrupted rest). Cumulative and average daily opioid use for postoperative days (POD) 1–4 were analyzed using ANOVA and a mixed effect model, respectively.
Results
Average daily opioid consumption and total cumulative opioid consumption POD 1–4 (morphine milligram equivalents) for both early and late ERAC groups (23.9 ± 31.1 and 29.4 ± 35.1) were significantly reduced compared to control and wound soaker groups (185.1 ± 93.7 and 134.8 ± 77.1) (p < .001).
Conclusion
The addition of ERAC protocols to our standardized multimodal analgesic regimen (local anesthetic wound infusion catheters and neuraxial morphine) for cesarean delivery significantly reduced postoperative opioid consumption.
Introduction
Achieving functional recovery after cesarean delivery is critical to a parturient’s ability to care for herself and her newborn. Although definitions of functional recovery vary slightly, the main tenets include regaining the ability to mobilize soon after delivery, the ability to provide self-care and to tolerate oral intake, all in the absence of any physical or laboratory derangements [Citation1–3]. Adequate pain control is vital in achieving these milestones, and without it, many other aspects of the recovery process may be delayed. However, opioid analgesics have many immediate systemic side effects like nausea, ileus, and sedation that can be just as distressing and may further hinder recovery and the ability to care for a newborn. The long-term consequences of these medications are even more jarring – in our home state of Colorado, drug overdose is consistently a leading cause of maternal mortality, and opioids are the most common offenders [Citation4–9]. As such, reducing opioid consumption without compromising analgesia is of paramount importance in this setting. Enhanced recovery pathways that incorporate interventions facilitating this have generated considerable interest.
Our group’s process for reducing opioid consumption evolved over time. We first demonstrated a reduction in opioid consumption after cesarean delivery by providing additional incisional pain control with the implementation of continuous bupivacaine infusions through wound catheters with the concurrent use of neuraxial morphine [Citation10]. We then introduced iterations of an enhanced recovery after cesarean (ERAC) delivery pathway after the Society for Obstetric Anesthesia and Perinatology’s consensus statement for ERAC was issued to eliminate variability in both hospital course and in the treatment of postoperative pain [Citation11]. In this retrospective cohort analysis, we sought to identify whether adding ERAC protocols to our existing combination of neuraxial morphine and wound soaker catheters further reduced opioid consumption after cesarean delivery.
Methods
The Colorado Multiple Institutional Review Board granted approval for this study, which was deemed exempt from review as it was not considered human subject research (COMIRB 21-2505). STROBE guidelines were followed.
We conducted a retrospective cohort analysis of all cesarean deliveries, including both scheduled and unplanned procedures, from 2015 through 2020 at the Colorado Fetal Care Center. To be eligible to deliver on our labor and delivery unit, a parturient must carry an anomalous fetus requiring post-delivery surgical and/or medical intervention, be free of maternal comorbidities producing end organ dysfunction, and be willing to accept blood products if needed. Our institution delivers approximately 300 newborns yearly with a cesarean delivery rate of 48%, which is largely due to fetal indications necessitating surgical delivery (i.e. omphalocele, hydrocephalus, unrepaired myelomeningocele, sacrococcygeal teratoma). Approximately 24% of all patients undergoing a trial of labor ultimately require cesarean delivery, which is consistently below the national average. Patients requiring general anesthesia, those that had previous mid-gestation fetal surgery or those that had any contraindication to neuraxial opioids were excluded from this analysis.
The anesthetic and surgical techniques for cesarean delivery are standardized and have been previously described [Citation10]. Intraoperatively, all patients receive 11 mg of bupivacaine 0.75% with dextrose, 15–25 µg fentanyl and 150 µg of preservative-free intrathecal morphine if a spinal is performed. If a trial of labor is attempted unsuccessfully with an epidural in place, patients are given 3 mg via epidural at the end of the procedure before epidural catheter removal. One dose of intravenous ketorolac 0.5 mg/kg (up to 30 mg) and intravenous acetaminophen 1000 mg are given at the end of the procedure (). Wound soakers are uniformly placed above the fascia and infuse bupivacaine 0.5% at a rate of 2 ml/h for 48 h post-cesarean delivery [Citation10]. These are fenestrated plastic catheters that allow for delivery of local anesthetic through tiny pores into the surrounding area. Placement in this fashion provides localized relief at the incision site and more wide-spread analgesia at the level of the anterior and lateral cutaneous branches of T10-L1 nerves.
Table 1. Multimodal analgesic regimen by perioperative period.
Methods of providing postoperative analgesia evolved over time and eventually incorporated iterations of an enhanced recovery after cesarean delivery (ERAC) protocol (; ). Deliveries were divided by analgesic pathway into four time-periods as follows – time-point 1 [January 2015-April 2016, previous standard of care (control)]: neuraxial morphine in addition to as needed opioid and non-opioid analgesics; time-point 2 [May 2016–May 2019, introduction of wound soaker (wound-soaker)]: continuous wound catheter infusions of local anesthetic and neuraxial morphine, in addition to as needed opioid and non-opioid analgesics not given at any specific time interval in relation to each other; time-point 3 [May 2019–December 2019, wound soaker + early ERAC pathway (early ERAC)]: continuous wound catheter infusion of local anesthetic and neuraxial morphine, in addition to scheduled non-opioid analgesics (acetaminophen and ibuprofen) every 6 h, alternating in relation to one another so that one is given every 3 h; time-point 4 [January 2020–July 2020, wound soaker + late ERAC pathway (late ERAC)]: continuous wound catheter infusion of local anesthetic and neuraxial morphine, in addition to non-opioid analgesics scheduled together every 6 h to facilitate periods of uninterrupted rest. Both early and late ERAC groups received intravenous opioids (fentanyl or hydromorphone) as needed for breakthrough (pain scores greater than 4) for the first 12 h. After this 12-h period, oral oxycodone 5–10 mg was given in place of intravenous opioids for breakthrough pain. In addition to other facets of our ERAC pathway, we also encouraged early ambulation, early advancement of diet, and early foley catheter removal (). The ERAC protocol that was implemented at our institution did not apply to vaginal deliveries and was adapted from the Society for Obstetric Anesthesia and Perinatology: Consensus Statement and Recommendations for Enhanced Recovery After Cesarean [Citation11].
Figure 1. Components of the enhanced recovery after cesarean delivery pathway. Preoperative, intraoperative, and postoperative components of the Enhanced Recovery After Cesarean Delivery Pathway
Statistical analysis
Our primary outcome was total cumulative opioid consumption over all postoperative days 1–4 [morphine milligram equivalents (MME)]. Our secondary outcome was daily opioid consumption for each postoperative day. Most patients maximized their length of stay to remain with their newborn during surgical/medical intervention. Those patients that were discharged home prior to POD 4 (<10%) were not included in our analysis of subsequent days. Most of these patients did not consume opioids within 24 h of discharge, and were, therefore, not sent home with an opioid prescription. Those that did require a prescription for opioids were only given 6–8 tablets of oxycodone 5 mg.
No a-priori power analysis was conducted to detect a specific effect size. With group sizes of 61, 40, 78 and 57, the minimum detectable effect size (Cohen’s f) is 0.22 for ANOVA analysis of the primary outcome. We believe that a post-hoc power analysis is irrelevant with interpreting the analysis results as discussed by Hoenig and Goodman [Citation12,Citation13].
Demographics and clinical data were displayed using standard descriptive statistics with either mean with standard deviation (SD) for continuous variables, or percentages for categorical variables (). These were compared across four groups using ANOVA for continuous variables. Chi squared tests or Fisher exact tests were used for categorical variables as appropriate. Comparison of cumulative postoperative opioid consumption across four groups was performed using ANOVA and ANCOVA, adjusting for gestational age at delivery and total intraoperative morphine milligram equivalents (; ). Appropriateness of normal assumptions were evaluated with a Shapiro-Wilk test and with examination of residual plots of statistical models. Non-parametric ANOVA and ANCOVA were also conducted for the total opioid consumption, as was a sensitivity analysis, which produced the same results as parametric models. For ease of clinical interpretation, parametric results are reported. Linear mixed models (LMM) with unstructured covariance were used to make within-group and between-group comparisons of daily opioid use over the four postoperative days. The LMM model consists of postoperative days and study group (both as classification variables) as well as their interaction term as predictors in unadjusted analysis. Further, a LMM model was conducted while adjusting for the potential confounding variables, gestational age and total intraoperative morphine milligram equivalents. Fisher’s least significant difference approach was used to adjust for multiple comparison. Significance level was set at .05. Statistical analyses were performed. SAS 9.4 (SAS Inc.; Cary, NC) was used for all statistical analysis.
Figure 2. Opioid consumption for postoperative days 1–4. Average daily morphine milligram equivalents divided by subgroup (control, wound soaker, early ERAC and late ERAC group) as a function of postoperative days 1–4. The blue line represents the control group and red dashed line represents the wound soaker group. The green and black dashed lines represent the early and late ERAC groups, respectively.
Table 2. Comparison of demographics between groups.
Table 3. Comparison of opioid consumption by group.
Results
During the study period there were 236 cesarean deliveries that met criteria for analysis – 61 in the control group, 40 in the wound soaker group, 78 in the early ERAC group, and 57 in the late ERAC group. Groups differed by a lower mean gestational age in the control group compared to the wound soaker group (, 35.5 ± 4.0 versus 36.9 ± 2.4, p = .03), smoking status, and in the incidence of anxiety/depression.
Patients in the control and wound soaker groups consumed more total opioids over POD 1–4 [morphine milligram equivalents (MME)] than the early and late ERAC groups (184.2 ± 92.9, 134.85 ± 77.1, 23.9 ± 31.1, 29.5 ± 35.1, respectively, p < .001). While opioid consumption was still high in the wound soaker group, there was still a 27% reduction in MME compared to the control group. On each postoperative day (1–4) there was a statistically significant reduction in total daily morphine milligram equivalents (MME) consumed in both early and late ERAC groups when compared to control and wound soaker groups ( and supplemental Table 4, , p < .001). However, total and average daily MME use between early and late ERAC groups was not statistically different. Additionally, 35% of patients in early and late ERAC groups utilized no opioids during their entire hospital stay except for neuraxial opioid administered intraoperatively (POD 0–4). There were no significant differences between groups regarding intraoperative or immediate postoperative (POD 0) intravenous opioids. In an adjusted model, these results remained consistent.
Discussion
Quality of recovery after cesarean delivery depends on multiple factors addressed in ERAC protocols, but a significant driver in effectively achieving functional recovery is adequate pain control. In the current climate of the opioid epidemic, newer innovative approaches to pain management that minimize opioid needs without compromising analgesia are necessary. Many of these methods have had variable success [Citation14–16]. Previously we demonstrated that the implementation of local anesthetic wound infusion catheters with the concurrent use of neuraxial morphine reduced postoperative opioid consumption after cesarean delivery by 30% [Citation10]. After the SOAP ERAC consensus statement was published, our approach then evolved to include these specific guidelines to our existing protocol [Citation11]. With these additional changes, we found that opioid consumption was even further reduced (over an 80% reduction in average MME consumed). These findings are consistent with what other ERAC studies have noted, but none included all key components of our multimodal approach, and none were performed at a fetal care center [Citation17–23].
There were no significant differences between groups regarding intraoperative or immediate postoperative (POD 0) intravenous opioids. Intraoperatively, all patients received the same analgesics, specifically neuraxial morphine, which we feel impacted the use of opioids (or lack thereof) in the immediate postoperative period (POD 0). Because morphine follows a biphasic half-life (early and late) in the cerebrospinal fluid, and its’ effect can last up to 12–20 h, we ascribe the distinct change in opioid consumption noted on POD 1 to its metabolism and eventual elimination; thus, emphasizing the distinct differences in analgesia provided by our other interventions on POD1.
When comparing non-opioid analgesics (acetaminophen and ibuprofen) administered every 3 h in an alternating fashion (early ERAC) to dosing both medications every 6 h (late ERAC), total opioid consumption was only slightly further reduced (80% versus 87%, ). Because this finding was likely not clinically significant, moving forward, we opted to dose non-opioid analgesics together every 6 h to minimize interruptions in sleep and self-care – both elements of recovery which are of critical importance. Although another benefit of enhanced recovery pathways is reduced length of stay, this remained unchanged between all groups and was expected. As mentioned previously, patients deliver anomalous newborns needing surgical intervention within the first 72 h of life; and, therefore, the typical length of stay is maximized to accommodate our patients’ needs.
Our study has many strengths. Because of the specialized care delivered in our unit, close monitoring of each patient possible. Additionally, our group consists of a small team of obstetricians, anesthesiologists, and nurses, with a select few championing the implementation of our protocols, reenforcing education and proper documentation. We feel that these unique circumstances allowed for making changes in protocol simple to circulate, standardize and implement, and also improved data accuracy and completeness.
While our study has many strengths, there are also several limitations. First, this is single center, retrospective observational study, and while randomized controlled trials are the gold standard, we would like to emphasize that our study is meant to provide a framework for other institutions to develop similar alternative pathways. The iterative process of making practice changes and assessing their impact on outcomes is a way to ensure delivery of high-quality care. Our study also does not investigate the post-discharge impact of ERAC pathways, specifically on long-term opioid use, the development of chronic pain, postpartum depression, breastfeeding success or neonatal safety. These are all incredibly important issues that should be factored into the way we care for patients. Future studies are being designed to assess if there are any long-term benefits of ERAC protocols with regard to these matters, especially since pregnant patients delivering at fetal care centers are unique, in that they are confronted with additional stressors to cope with regard to the outcome of their anomalous fetuses.
In summary we found that the addition of an ERAC pathway to our standard regimen of wound soakers and neuraxial morphine resulted in a significant reduction in opioid consumption after cesarean delivery. Because we do not know the impact that our ERAC pathway alone may have had on opioid consumption, a double-blind randomized control trial (NCT05131178) is now being undertaken to address this question.
Supplemental Material
Download MS Word (16.8 KB)Acknowledgements
The authors would like to acknowledge Marilyn Hernandez, RN for her substantial contributions to the conception of this project, and the acquisition of data for analysis.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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