In the present study, we evaluated the utilization of neuraxial morphine with temporal trends over a 15-year period and described the current postoperative analgesia practice. Our analysis revealed that the prevalence of neuraxial morphine was 16.0% in the overall cohort. Intrathecal morphine was used in 20.6% of spinal anesthesia cases. The usage rate of neuraxial morphine steadily increased from 2005 to 2020. Moreover, the significant predictors of neuraxial morphine use included spinal anesthesia, recent surgery, large medical facilities, and academic hospitals.
The increasing rate of cesarean deliveries worldwide and in Japan warrants anesthesiologists to deliver safe and high-quality anesthetic care during the perioperative period. Recently, enhanced recovery after cesarean delivery (ERAC) has been introduced and has become the standard for improving the quality of perioperative care and patient satisfaction in cesarean deliveries . Among the components of the ERAC, neuraxial morphine and multimodal opioid-sparing analgesia are recommended to improve the quality of care for cesarean deliveries and promote patient recovery after childbirth. However, several knowledge gaps in the current post-cesarean delivery analgesia practice still exist. First, detailed information on the current analgesia practices for cesarean deliveries in diverse nationwide facilities is limited. Therefore, a trend analysis of the use of neuraxial morphine in cesarean deliveries and a descriptive study of the current postoperative management practices are valuable for examining the quality of perioperative maternal health care. Second, patient- and facility-specific factors associated with the use of neuraxial morphine are unknown. This information could help identify barriers to standardizing the use of neuraxial morphine and improving perioperative analgesic management.
Neuraxial morphine and multimodal analgesia are the gold standards for pain management after cesarean delivery. No study has reported the exact number of women undergoing cesarean delivery who received neuraxial morphine in Japan. Our data demonstrated that, during the whole study period, neuraxial morphine was used in 16.0% of cesarean deliveries; the usage rate of neuraxial morphine, especially intrathecal morphine, gradually increased and its administration has become the standard practice. These trends were consistent with those obtained from the United States (US) and Europe, but the rate of neuraxial opioid use in Japan was comparatively lower than those of the US (71.4% in 2008 and 83.4% in 2018 ) and European countries (71% in Austria ). Our results demonstrated that recent surgeries (especially 2015–2020) were strongly associated with the utilization of neuraxial morphine. The trend in neuraxial morphine use is important in establishing benchmarks and could provide invaluable information to help clinicians and patients in shared decision-making for post-cesarean delivery analgesia .
In the components of the ERAC, the use of postoperative multimodal analgesia is important to avoid inappropriate opioid use and to improve maternal satisfaction. Our data demonstrated that the usage of NSAIDs plus acetaminophen and NSAIDs plus acetaminophen–opioid combination were 31.5% and 0.4%, respectively. In a cohort study conducted in the US, the usage of NSAIDs plus acetaminophen and NSAIDs plus acetaminophen–opioid combination were reported as 8.1% and 76.7%, respectively . In the previous study, 81.3% of cesarean delivery cases received acetaminophen–opioid combination drugs and only 28.4% received acetaminophen . Recent studies have shown that 89% of women undergoing cesarean deliveries use some form of opioid for postoperative pain, which has become a social problem, especially in the US . Compared to the US cohort, our cohort was seldom prescribed acetaminophen/tramadol combinations (the only available acetaminophen–opioid combination in Japan) and tramadol (< 1%). Additionally, hydrocodone, hydromorphone, methadone, oxymorphone, oxycodone, and tapentadol were not prescribed in our cohort. This is consistent with the result of a recent survey in Japan; the usage of opioids for postoperative analgesia is substantially lower in Japan than in Western countries because of culture and strict government regulations . Therefore, postoperative opioids are rarely administered in Japan. These results are highly contrasting and indicate a completely different opioid prescribing pattern compared to those in the US .
The group who did not receive neuraxial morphine was more likely to receive continuous epidural analgesia, opioids (buprenorphine and pentazocine), and ketamine compared with the group who received neuraxial morphine. The group who did not receive neuraxial morphine may need long-acting analgesia, such as continuous epidural analgesia, and supplemental analgesia, such as buprenorphine, pentazocine, or ketamine, for post-cesarean delivery analgesia. Conversely, as the neuraxial morphine group used NSAIDs plus acetaminophen more frequently (36.2% [with neuraxial morphine] vs. 30.6% [without neuraxial morphine]), these results reflect the current trend in the concept of multimodal analgesia. In the US, ketorolac, diclofenac, and ibuprofen are typical NSAIDs , but their use is infrequent in Japan. Instead, the essential components of multimodal post-cesarean delivery analgesia include diclofenac and loxoprofen, which are widely used during the postpartum period. As our data do not clearly distinguish scheduling administration of NSAIDs and acetaminophen, the combined administration of NSAIDs and acetaminophen was used in only 31.5% of our cohort. A previous study in the US showed that 76.7% of patients received NSAIDs and acetaminophen–opioid combination drugs . Given that the prevalence of multimodal analgesia use in Japan is very low compared to that of the US and that there is a variation in the utilization of postoperative analgesia among women undergoing cesarean deliveries, standardization of postoperative pain management after cesarean delivery is warranted to improve the quality of care and patient satisfaction.
Our results showed that neuraxial morphine use was strongly associated with facility-level characteristics, such as facility size and academic hospital status. Our results also showed that patient-level factors, such as age and maternal comorbidities, could not predict the use of neuraxial morphine. However, the influence of non-medical factors (fiscal year, facility size, and academic hospital status) persisted, even after adjustment, suggesting that non-medical factors are important predictors of neuraxial morphine use. The exact mechanism of this increasing trend in neuraxial morphine use cannot be explained by our data, but, in recent years, the development of subspecialty education in the field of obstetric anesthesia in large medical facilities, especially academic hospitals, may play an important role in raising awareness of the superior analgesic quality.
The strength of our study is that it is the largest nationwide study to include diverse facilities and reflects the current real-world practice to date in Japan. The JMDC database is limited to the employee-based health insured population; however, Japan has universal health coverage system and free access to medical facilities. Hence, different types of health insurance or racial/socioeconomic disparities would not influence our results. Thus, our results can generalize to the majority of pregnant women undergoing cesarean deliveries in Japan . Additionally, our large sample size and low rate of missing cases can precisely estimate the patient- and facility-specific factors associated with neuraxial morphine use in clinical practice.
This study has several limitations. First, our definition of neuraxial morphine can be influenced by coding errors or misclassifications, which could lead to a potential misclassification bias. To reduce misclassification bias, we defined neuraxial morphine as a morphine dose in vials of ≤ 10 mg based on a previous study  because a higher morphine dose (> 10 mg) may indicate possible contamination due to intravenous administration of postoperative patient-controlled analgesia. However, as this practice is uncommon in Japan, our large sample size can mitigate this influence on our outcomes. Another limitation is the time span of our dataset. As the data were collected between 2005 and 2020, the trend in analgesic use or available drugs has changed; therefore, it is uncertain to what degree the rates of postoperative analgesia use have changed since 2005. However, as there is a surprising lack of nationwide data on the rates of neuraxial morphine use for cesarean deliveries, our findings provide the best available evidence for the current obstetric anesthesia practice in Japan. Finally, the perinatal care system and obstetric anesthesia practices in Japan are completely different from those of Western countries. A previous government survey found that 31% of cesarean deliveries were performed in small facilities (< 20 beds) . Compared to other Western countries, Japanese health care system has an insufficient functional differentiation between hospitals and clinics .
In conclusion, our data could be useful for identifying the current trend in neuraxial morphine administration and the variation in postoperative analgesia practice in Japan for over 15 years. Moreover, our data provide valuable information for the standardization of post-cesarean delivery analgesia practice, as we compared national and global data.