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Abstract
Background During the postoperative period of elective cesarean section, intrathecal morphine is effective in the multimodal analgesic regimen, but can cause significant adverse effects. Bilateral posterior quadratus lumborum block could be alternatively used. The aim of this study was to compare efficacy and safety of both strategies as part of a multimodal analgesic regimen.
Methods This was a prospective, randomized, blinded, controlled study. 104 parturients were randomly selected to receive intrathecal morphine or posterior quadratus lumborum block during cesarean section under spinal anesthesia. The primary endpoint was patient-controlled 24-hour cumulative intravenous morphine use. Secondary endpoints were 48-hour cumulative morphine use, static/dynamic pain scores, functional recovery (ObsQoR-11 questionnaire) and adverse effects.
Results There was no statistical difference in the mean cumulative morphine dose at 24-hour between groups (posterior quadratus lumborum block group, 13.7 (97.5% CI 10.4 to 16.9) mg; intrathecal morphine group, 11.1 (97.5% CI 8.4 to 13.8) mg, p=0.111). Pain scores did not show any difference between groups, excepted at 6 hours for the pain at cough/movement in favor of the posterior quadratus lumborum block group (p=0.013). A better recovery quality was observed at 24 hours in the posterior quadratus lumborum block group (p=0.009). Pruritus was more frequent in intrathecal morphine group parturients (35% vs 2%)
Conclusions No difference in cumulative morphine dose at 24 hours was observed in posterior quadratus lumborum block group compared with intrathecal morphine group. Posterior quadratus lumborum block can be considered an alternative to intrathecal morphine in cesarean postoperative analgesia, especially in cases of intolerance to morphine.
Trial registration number NCT04755712.
- Obstetrics
- Analgesia
- Pain, Postoperative
- Opioids
- Nerve Block
Data availability statement
Data are available upon reasonable request. All data generated or analyzed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Intrathecal morphine is commonly used as a mechanism for postoperative analgesia following cesarean section surgery. However, the drug has significant side effects making alternative techniques warranted.
WHAT THIS STUDY ADDS
Our study suggests that analgesia is similar between bilateral posterior quadratus lumborum block and intrathecal morphine with a better side effect profile.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Bilateral posterior quadratus lumborum block can be seen as a valuable alternative for patients undergoing cesarean section surgery, especially if sensitive to the adverse effects of opioids.
Introduction
Cesarean section (CS) is an intervention associated with significant postoperative pain.
Its management is crucial to avoid the installation of chronic pain, greater opioid use, delayed functional recovery, alteration of the mother–child bond and increased risk of postpartum depression.1 Whether it is scheduled or performed in an emergency setting, CS is usually implemented under neuraxial anesthesia to avoid the maternal and fetal risks of general anesthesia. Thus, in scheduled CS, the recommended anesthesia protocol is spinal anesthesia with addition of intrathecal morphine (ITM) coupled with non-opioid multimodal postoperative analgesia, such as non-steroidal anti-inflammatory drugs and paracetamol.2 However, its use is associated with side effects like nausea, vomiting and pruritus and does not always result in avoiding the use of oral opioids postoperatively.
Many complementary local or regional analgesia techniques have been described3 with controversial results on the reduction of postoperative pain.4–6 The quadratus lumborum block (QLB) seems to be an interesting alternative to the ITM7–10 as the transversus abdominis plane block.11 12 In this case, the injection of local anesthetic is performed under ultrasound near the quadratus lumborum (QL) muscle, at the crossroads of the abdominal parietal innervation.3 Multiple meta-analyses attest to the difficulty of comparing QLB results due to the differences in studies procedure and the various non-intramuscular QLB approaches (lateral, posterior, anterior).13–15 In 2019, bilateral posterior QLB (PQLB)16 was determined to be easier and less risky than the anterior approach, which requires a deeper injection, in closer proximity to the areas at risk.11 This diffusion allows analgesia of the last intercostal nerves and of the ilioinguinal and iliohypogastric nerves (coming from the T12 and L1 roots),17 ideal for Transverse Pfannenstiel or Joel Cohen incision. Moreover, PQLB can possibly be extended to other anterior rami of spinal nerves and have an effect on visceral innervation of the uterus,11 which may be sympathetically mediated,18 yet limited evidence supports this theory. An extension to the thoracic paravertebral space could be possible with a QLB. However, findings in PQLB and ITM analgesia studies are heterogeneous.14 15 19–25
Four studies compared PQLB to ITM19–22 and showed contrasting results on morphine consumption, pain scores and time to first morphine request, making conclusions difficult. It is essential to identify effective postoperative pain control strategies that facilitate early recovery and hospital discharge with minimal side effects for the mother and infant.
Ropivacaine has long-term action, and its use in postoperative analgesia of CS has been widely described.8–10 12 13 21 22 The aim of this study was to assess whether ropivacaine administered in PQLB is more effective in postoperative analgesia of CS compared with ITM.
Methods
Study design and participants
This randomized, blinded, prospective study conducted in one department of anesthesia in France is registered on ClinicalTrials.gov on 12 February 2021. The first patient was included on 22 March 2021. The study included women aged 18 years or over, with the American Society of Anesthesiologists’ physical status <3. They had to be eligible for a scheduled CS under spinal anesthesia, for the birth of a full-term baby with a Pfannenstiel-type incision. Key exclusion criteria were pregnancy of <37 weeks of amenorrhea; multiple pregnancy; known fetal pathology at the time of inclusion; body mass index (BMI) >45 kg/m²; chronic pain associated with opioid consumption; general contraindications specific to spinal anesthesia, independently of the local anesthetic used. Parturients provided written, informed consent before any study-related procedure. Online supplemental table S1 presents the extensive list of eligibility criteria.
Supplemental material
Procedure
Spinal anesthesia and drugs delivered during the CS
Spinal anesthesia was induced at h-0 by intrathecal injection with bupivacaine 10 mg (2 mL at 5 mg/mL) and sufentanil 2.5 µg (0.5 mL to 5 µg/mL). Antibioprophylaxis by slow intravenous cefazoline 2 g (or clindamycine 900 mg in case of allergy) started 30 min before incision time. Prophylactic oral cimetidine 200 mg (two tabs) was taken at the same time. Intravenous norepinephrine 16 µg/mL was used as necessary to maintain mean arterial pressure within 90% up to basal value. Slow intravenous dexamethasone 4 mg/mL was injected before fetal extraction and droperidol 1.25 mg/mL after umbilical cord snapping.
Slow intravenous carbetocin 100 µg/mL was used to prevent excessive bleeding after childbirth. All abdomens were prepared aseptically.
Postoperatively, parturients were given intravenous paracetamol 1 g and ketoprofen 100 mg (h-1).
On exiting the recovery room, women benefited from a morphine pump allowing 1 mg intravenous administration by bolus per request (patient-controlled analgesia or PCA). A maximum of 6 mg/hour was authorized. The pump was removed at hour 24. Oral paracetamol 1 g and ketoprofen LP 100 mg were systematically prescribed from hour 6 for 48 hours for per request consumption. From hour 24, morphine was administered per os if needed. Any oral morphine administered between hour 24 and hour 48 has been converted to intravenous morphine equivalent.
Analgesic strategies
Ropivacaine (Fresenius Kabi France, Sèvres, France) and morphine chlorhydrate (Aguettant, Lyon, France) were prepared and used according to summary of product characteristics.
Standard strategy: ITM
Morphine chlorhydrate 0.1 mg/mL was used in a unique intrathecal injection of 1 mL. The injection is performed before CS, during spinal anesthesia (in the same syringe as bupivacaine and sufentanil). Parturients also received in the recovery room a bilateral subcutaneous echoguided injection of chloride saline solution in the PQLB injection area to satisfy patient blinding to the randomly assigned strategy.
Experimental strategy: ropivacaine in bilateral PQLB
Ropivacaine 3.5 mg/mL was obtained by mixing two vials of 10 mL at 5 mg/mL with one vial of 20 mL at 2 mg/mL. Total volume administered was 40 mL (20 mL/side) corresponding to a dose of 140 mg.
All women had their abdominal wall imaged using a curvilinear 2–6 MHz ultrasound transducer (LOGIQ E10s, General Electric Healthcare). Echo-guided injections of ropivacaine were performed with an 80 mm needle (B-braun, Ultraplex 360) in PQLB in the lateral decubitus position in the recovery room 1–2 hours after spinal anesthesia, depending on the CS duration. The product was injected into a myofascial space between the posterior aponeurosis of the QL muscle and the middle layer of the thoracolumbar fascia. The local anesthetic then diffused not only along the QL muscle in the cephalo-caudal direction but also around the muscle in the transverse direction.
Assessments
Inclusion and randomization were performed within 24 hours of CS. The primary outcome measure was hour 24 total cumulative intravenous morphine use. Secondary endpoints included: hour 6, hour 12 and hour 48 total cumulative morphine use, time to first morphine requirement, pain severity (assessed by visual analogic scale, 0–100 mm) at rest and when coughing/on movement at hour 1, hour 6, hour 12, hour 24 and hour 48. Functional recovery was analyzed at hour 24 and hour 48 by the global score of the Obstetric Quality-of-Recovery (ObsQoR-11) questionnaire, which covers four domains of recovery outcomes (physical comfort, emotional state, physical independence and care of the neonate, and pain).26 Secondary safety endpoint included side effects or adverse effects (AE).
Method of randomization and blinding
Consenting parturients were allocated randomly to ITM group or PQLB group for postoperative analgesia. A randomization sequence was computer generated at the statistical Unit, Euraxi, France. Participants and investigators were blinded to the analgesia used. Only the anesthesiologist in charge of the procedure received the group allocated to the patient to perform the anesthesia. This one could not be the same as the anesthetist investigator that informed and enrolled the patient into the study or collect patient data.
No sensitive testing was performed during the procedure to maintain the patient blinding. Assessments performed after the CS were carried out by masked operators.
The study was performed according to the International Conference on Harmonization of Good Clinical Practice guidelines and the principles of the Declaration of Helsinki.27 Authorization of the Competent Authority and approval from the ethics committee were obtained prior to study start.
Sample size
Sample size calculation was based on the cumulative intravenous morphine dose at h-24 and determined assuming an estimated mean dose of 20 mg in the ITM group28 and 10 mg in the QLB one,29 with a 15 mg SD. The hypotheses tested are as follows: null hypothesis (H0): (PQLB dose - ITM dose) ≥ 0 mg, and alternative hypothesis (H1): (PQLB dose - ITM dose) < 0 mg. Considering a SD of 15 mg for the difference between groups, a minimum of 49 women/group was required to conclude on QLB superiority when setting the two-sided alpha risk (α) and the power (β) to 0.05 and 0.1, respectively. Considering a 5% of non-evaluable subject (premature withdrawal, missing data), 104 inclusions were required (52/group).
Statistical methods
Differences of mean cumulative morphine dose at hour 24 were calculated with 95% CIs. We analyzed results on an intent-to-treat (ITT) basis. Statistical analyses were performed using SAS (V.9.4, SAS Institute, Cary, North Carolina).
Normally distributed data according to the Shapiro-Wilk test (represented as mean (SD)) were assessed using the Student’s t-test (two-tailed, equal variances) and non-normally distributed data (represented as median (range)) were assessed using the Mann-Whitney U or Satterthwaite test. Ordinal data were represented as median and IQR.
The evolution of cumulative morphine doses, pain scores at rest and on movement and ObsQoR-11 scores over time were analyzed using a mixed model of Repeated Measurements (MMRM) including treatment group, time and interaction between these variables as covariates. Least square means and their 95% CI were calculated for each timepoint.
A p value <0.05 was considered statistically significant.
Results
Between 22 March 2021 and October 2022, 104 women were enrolled. Three were ineligible (scheduled cesarean finally not necessary (n=2), allergy or contraindication to one study treatment (n=1)). Out of the 101 eligible parturients, 50 were randomized to PQLB (49.5%). None was excluded for protocol deviation. One woman prematurely withdrew the study due to the occurrence of a serious adverse event (hemorrhage following uterine rupture). The flowchart of the study is presented in figure 1.
CONSORT flow diagram. CONSORT, consolidated standards of reporting trials; CS, cesarean section; ITM, intrathecal morphine; PCA, patient-controlled analgesia; PQLB, posterior quadratus lumborum block.
Median (IQR) age was 33 (29.0–35.0) years old. The median (IQR) BMI before pregnancy was 26.6 (23.8–31.2). There were more obese women in PQLB (36.0%) than in ITM group (27.5%). Table 1 presents parturient and pregnancy characteristics at baseline. Anesthesia and CS characteristics are presented in online supplemental table S2.
Baseline parturients’ characteristics allocated to PQLB or ITM group
All participants received spinal anesthesia. Mean CS and anesthesia durations were, respectively, 59.4 (12.0) and 21.6 (6.8) min. All auxiliary medications were administered according to protocol. Metoclopramide was not given to 92.1% of parturients due to the absence of postoperative nausea. Seven women (one in PQLB and six in ITM group) experienced pain >3 on a visual analog scale in recovery room postanesthesia care unit, requiring intravenous morphine (online supplemental table S3).
Primary endpoint
The mean total cumulative intravenous morphine use during postoperative 24 hours was not statistically different between groups (PQLB, 13.7 (11.4) (97.5% CI 10.4 to 16.9) mg; ITM, 11.1 (9.6) (97.5% CI 8.4 to 13.8) mg, p=0.111).
Secondary endpoints
Cumulative dose of morphine across timepoints was not significantly different between groups (p=0.06, 0.06, 0.63, 0.42 and 0.28, respectively). Table 2 and online supplemental figure S1 illustrate the results.
Cumulative morphine dose administered from h-1 to h-48 (intent-to-treat population)
Static pain severity at hour 1, hour 6, hour 12, hour 24 and hour 48 was not significantly different between groups, unlike when coughing/on movement (dynamic pain) where it was higher in the ITM group at hour 6 (p=0.013) (table 3 and figure 2). The MMRM confirmed the results (p=0.01). Moreover, more women were able to get up from bed at hour 6 (14.3% vs 5.9%).
Pain intensity (VAS 0–100 mm) at rest and when coughing/on movement from h-1 to h-48 by groups (intent-to-treat population)
Postoperative pain intensity scores by group (a) at rest and (b) at cough/movement for 48 hours. Data are means with error bars showing SD Pain was assessed using a visual Analog Scale (0–10). *P value<0.05 PQLB vs ITM. H, hour; ITM, intrathecal morphine; PQLB, posterior quadratus lumborum block.
The mean time to first PCA morphine requirement was significantly longer in PQLB group (9.23±9.08 hours vs 5.26±5.43 hours, p=0.01) (table 4).
Time to first PCA morphine requirement, Obs-QoR-11 scores at h-24 and h-48, and adverse effects by groups (intent-to-treat population)
In the quality of functional recovery, there was a significative difference in ObsQoR-11 scores between groups at hour 24 in favor of the PQLB (p=0.01), unlike at hour 48 (p=0.10). There was a significant improvement in ObsQoR-11 score at hour 48 compared with hour 24 in both groups (84.7 to 91.1 in PQLB vs 75.6 to 85.7 in ITM group) (table 4 and figure 3).
Obs-QoR-11 scores by groups (Intent-to-treat population) (a) at h-24 and (b) at h-48. Each of the 11 axes represents a dimension of the ObsQoR-11. The central point corresponds to a mean score of 0 and the higher the mean score, the further the point is from the center of the radar. *P value<0.05 PQLB vs ITM. ITM, intrathecal morphine; ObsQoR-11, Obstetric Quality-of-Recovery; PQLB, posterior quadratus lumborum block.
Regarding safety endpoint, 32% of parturients experienced an AE in the PQLB group, unlike the ITM group where they were 58.8%. Pruritus was the main AE observed in ITM group (60%) (table 4). No serious AEs related to PQLB occurred, nor local anesthesia toxicity syndrome. No muscle deficit of the lower limb and falls were observed after PQLB.
Discussion
Our study demonstrated that both PQLB and ITM are effective in pain management after CS but failed to demonstrate superiority of PQLB on hour 24 morphine PCA consumption, confirming the previous results.19
Using a QLB anterior approach would likely have yielded a more favorable outcome according to the latest meta-analysis published in 2023.30 Indeed, an injection into the anterior surface of the QL muscle, closer to the anterior rami of spinal nerves, is more likely to be effective, with potentially greater cephalo-caudal extension. Recent studies have supported the efficacy of the anterior QLB, although it was still under consideration during the design of this study in 2019. Additionally, the greater distance from high-risk areas such as the kidney and retroperitoneal space, along with the more superficial nature of the injection, makes the technique easier to perform and reduces associated risks. Based on our experience, the PQLB was routinely performed in our center.
In the Salama and colleagues’ study, the PCA morphine requirement favored the PQLB group (ropivacaine, 2×24 mL at 0.375%) at hour 4821 on a small population (30/group), with no data available at hour 12 and hour 24. Diverging published results may be explained by study heterogeneity and differences in local anesthetic dose and volume as well as PQLB approach used.7 13 20 21 30 The use of a PCA was chosen to control the need for morphine dose and standardize administration without bias of nursing staff actions.
However, our study confirmed that early postoperative analgesia with a PQLB approach might be beneficial because dynamic pain was lower at hour 6, as previously published19 21 22 and the time to first morphine requirement was also longer, as previously observed.20 21 We do not demonstrate any difference on pain intensity at rest as observed in recent systematic review and meta-analysis.14 23 25 An explanation for the lack of significant differences in postoperative pain could be a limited spread into the paravertebral space and thus limited action on visceral pain.
Postoperative functional recovery is a relevant endpoint to reinforce the results or trends observed on postoperative pain intensity. In this study, the recovery was better at hour 24 in the PQLB group compared with ITM group. Moreover, more women were able to get up from bed at hour 6 confirming Salama and colleagues results.21 In this way, the mother might take care of her baby earlier, which is a major element in post-CS recovery and in the creation of the mother–child bond. Breast feeding success may have been included as secondary endpoints.
Regarding side effects, the experimental strategy generated fewer pruritus, which can be bothersome for the parturient. Postoperative nausea and vomiting were rare due to an effective antiemetic prophylaxis. Safety data were coherent with previous published work comparing ITM and PQLB.21 22 24
This study had several limitations. First, the statistical hypothesis based on an expected 50% reduction in hour 24 morphine consumption was estimated with current literature available in 2019, at the study design conception, and with our own data collected from an insufficient number of patients (n=15) and no sophisticated design (ie, randomization and blindness). Further publications including a meta-analysis in 2021 showed that it was clearly overestimated. All parturients received sufentanil, which produces early analgesia mainly during the first hours after CS, associated with AE resembling those of ITM. The study design was not ‘double-blind’. In the absence of intrathecal placebo, the operator was informed of the allocation group. We wanted to avoid manipulations at the intrathecal injection level as much as possible to minimize the septic risk. Only the patient and the evaluator were ‘blinded’. There was no sensory testing for evaluating block success performed in our study to preserve the blinding of group allocation. However, all PQLB procedures were filmed and reviewed subsequently by an experienced operator (TG) to verify that the QLB was performed accurately. The monocentric nature of the study prevents results generalizability.
PQLB following CS remains difficult to perform and requires expertize and ultrasound available. Another significant challenge in performing the PQLB is the need to position the patient in a lateral decubitus position on both sides at the end of surgery. This requires substantial human resources and additional materials (eg, needles for extra punctures). Additionally, the PQLB technique can cause patient discomfort, while performing ITM simultaneously with spinal anesthesia is often simpler and faster. To note, there were more obese parturients in the PQLB group (36.0% vs 27.5%) in our study, which could have made performing the PQLB more difficult and had an impact on the success of the analgesia.
Taking all the results together, it could be hypothesized that PQLB has a shorter time of effectiveness than ITM, estimated to approximately 12 hours in a systematic review.25 The possibility of extending the analgesic duration of PQLB using adjuvants or use of perineural catheters for continuous ropivacaine administration might be interesting and needs further investigations.
Conclusions
In this study, both PQLB and ITM were effective for post-CS analgesia, although PQLB provided no advantage over ITM in terms of morphine consumption during the first 24 hours or pain at rest. Nonetheless, less pruritus was observed in the PQLB group. The PQLB can be seen as a valuable alternative for CS parturients sensitive to the AEs of opioids. This study highlights its potential beneficial effects on lasting analgesia, pain on movement and recovery in the first postoperative hours, which will need to be investigated in further studies using an adequate power calculation.
Supplementary video
Supplementary video
Data availability statement
Data are available upon reasonable request. All data generated or analyzed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by East-III Ethics Committee ID number: 21.01.07. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors would like to thank the Research and Education Department of Ramsay Santé (sponsor). The authors would also like to thank Dr Luc Mercadal and Nadine Lubango for their co-operation during this study, as well as Ms Cécile Bultez and Ms Irina Filippi for conduct management and medical writing support and Mr Mohammed Aqlan and Mr Benoit Berge for the statistical analysis of the study.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors All authors significantly contributed to the study.
Funding This study was funded by GCS Ramsay Santé pour l'enseignement et la Recherche (Grant number: COS-RGDS-2019-12-006-P-MAUPAIN-O).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer-reviewed.
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