Investigation of the effect of ultrasonography-guided bilateral erector spinae plane block on postoperative opioid consumption and pain scores in patients undergoing hepatectomy: a prospective, randomized, controlled study

ABSTRACT BACKGROUND: There is still a debate about what constitutes effective and safe postoperative analgesia in hepatectomy surgery. Erector spinae plane (ESP) block may be an important part of multimodal analgesia application in hepatectomy surgery. OBJECTIVES: To compare the effects of ultrasound-guided bilateral erector spinae plane block combined with intravenous (iv) patient-controlled analgesia (iv PCA), in comparison with iv PCA alone, in hepatectomy surgery. DESIGN AND SETTINGS: Randomized prospective single-blinded study in a tertiary university hospital. METHODS: Fifty patients scheduled for elective hepatectomy surgery were included in the study. Patients were randomized into the ESP group or the control group. In the ESP group, bilateral ESP block was performed preoperatively and iv PCA was used. In the control group, only iv PCA was used. Numerical rating scale (NRS) scores at rest and coughing, analgesic requirements and occurrences of nausea and vomiting were recorded. RESULTS: Intraoperative and postoperative opioid consumption, rescue analgesia requirement and resting and dynamic NRS scores were significantly lower in the ESP group (P < 0.05). There was no significant difference between two groups in terms of the presence of dynamic pain after the first postoperative hour. While all patients in the control group had nausea and vomiting, 24% of the patients in the ESP group did not have nausea and vomiting. CONCLUSION: This study showed that ESP block can be used as a part of multimodal analgesia, with the benefit of reducing opioid consumption and postoperative nausea and vomiting in hepatectomy surgery. CLINICAL TRIAL REGISTRATION: ACTRN12620000466943.

number of randomized clinical studies indicating the effectiveness of this block in hepatectomy surgery is limited. 8,9 To the best of our knowledge, there are no clinical studies in the literature researching the effectiveness of ESP block in hepatectomies carried out with bilateral subcostal incision. Therefore, we conducted a prospective randomized clinical study, with the prediction that an ESP block at T8 level, in addition to the iv morphine therapy that we apply in our routine practice in hepatectomies carried out with bilateral subcostal incision, would reduce postoperative opioid consumption and pain scores.

OBJECTIVE
The aim of this study was to compare the effect of ultrasoundguided bilateral erector spinae plane block combined with iv PCA, in comparison with iv PCA alone, in hepatectomy surgery.

Study design
This study was designed in an academic university hospital as a prospective randomized controlled single-blinded study, in accordance with the principles defined in the Helsinki Declaration. The study was conducted after obtaining approv- Patients between the ages of 18 and 65 years, presenting with American Society of Anesthesiologists (ASA) physical status I-III, who had been scheduled to undergo elective hepatectomy surgery in which bilateral subcostal incision would be used as the surgical incision, and for whom a self-retaining retractor would be used, were included in the study. Patients were excluded from the study in the following circumstances: obesity (body mass index > 30 kg/m 2 ); local skin infection in the area where the needle would be inserted; known allergy to any of the drugs to be used in the study; coagulopathy; chronic opioid consumption; inability to use the PCA device; advanced liver failure; kidney failure; or lack of agreement to participate in the study.

Patient groups and randomization
The patients were randomized and grouped by using the sealed opaque envelope technique. A researcher who was not included in the study performed this procedure. The patients who would not have the block and would only use an iv PCA device for postoperative analgesia comprised the control group. The patients who would undergo preoperative bilateral ESP block and use an iv PCA device postoperatively comprised the ESP group.

Anesthesia application
The same general anesthesia method was applied to all the patients, and the hepatectomy operation was carried out by the same surgical team. Before the operation, all the patients were told about numerical rating scale (NRS) scores for assessing their postoperative pain severity and how to use the iv PCA device.
The patients' demographic data and ASA scores were recorded. and infusion of remifentanil. The analgesic requirement was monitored using the surgical pleth index (SPI) (SJB17230028HA, GE Healthcare, Helsinki, Finland); the remifentanil infusion dose was set to a SPI below 50; and the total intraoperative remifentanil consumption was recorded.
The patients underwent invasive artery monitoring and right internal jugular vein catheterization via ultrasonography.
The surgery was carried out by making a bilateral subcostal incision and using a self-retaining retractor. The duration of the surgery and the surgery performed (right hepatectomy or left hepatectomy) were recorded.
Thirty minutes before the end of the operation, 0.1 mg/kg of iv morphine (Morphine HCl, Idol, Istanbul, Turkey) was admin- Here, an iv PCA device (BodyGuard 575 Pain Manager, Caesarea Medical Electronics GmbH, Lichtenstein, Germany) was attached to patients for postoperative analgesia. PCA was programmed as 1 mg/ml of morphine without a basal infusion dose, as 1 ml per bolus, with a lock-out time of six minutes. Patients were followed up until their modified Aldrete score reached 9 in the PACU and were then transferred to the intensive care unit of the related clinic.

ESP block application
All the blocks were carried out about 30 minutes before induction of anesthesia. This was done by researchers who would not monitor the postoperative data from the patients (GH, AT).
The patients were placed in the prone position, and the skin was prepared with 10% povidone iodine (Poviderm, Necm Chemistry, Istanbul, Turkey). The position of the T7 vertebra at the level of the lower ends of the scapula was determined, and the T8 vertebra one level below this was then detected by palpation.
The T8 spinous process was first seen in the horizontal plane on the midline by using a linear probe covered with a sterile cover at 8 mHz frequency, by means of ultrasonography (Esaote MyLab Six CrystaLine, Genova, Italy). The probe was then turned to the longitudinal plane, and the transverse process was seen approximately 3 cm from the midline to the left lateral and the erector spinae muscle was seen on it.
A 22-gauge 80-mm block needle (Sonoplex, Pajunk Medical, Geisingen, Germany) was advanced craniocaudally in-plane, and the transverse process was touched. The needle was then minimally retracted, and its positioning between the erector spinae muscle and the transverse process was confirmed through hydro-dissection. Following this, 20 ml of 0.375% bupivacaine hydrochloride (Buvicaine, Polifarma, Tekirdağ, Turkey) + 4 mg of dexamethasone (Dekort, Deva, Tekirdağ, Turkey) were injected, and simultaneous local anesthetic dispersion was monitored by means of ultrasonography. The same procedure was performed on the right side.
Loss of hot-cold sensation below and above the bilateral T8 dermatome level, 20 minutes after the block had been performed, was considered to represent successful blocking. The blocked dermatome levels were recorded.

Pain assessment and analgesia protocol
Postoperative pain scores and analgesic requirements were assessed by a research assistant who was blinded to the groups, in the PACU and surgical service.

Primary and secondary outcome criteria
The primary outcome criterion of the study was total morphine consumption over the first postoperative 24 hours. The secondary outcome criteria were the resting and dynamic NRS scores at five different time points (postoperative 10 th minute, 1 st hour, 6 th hour, 12 th hour and 24 th hour), intraoperative remifentanil consumption and total rescue analgesic requirement over the first postoperative 24 hours. Besides these measurements, changes in the presence of dynamic pain, postoperative nausea-vomiting, dermatome levels in patients who underwent the block, duration of surgery and surgery applied (right hepatectomy or left hepatectomy) were also evaluated.

Sample size calculation
The sample size for this study was calculated using the G*Power

Statistical analysis
The data obtained in this study were evaluated using the If P < 0.05, it was accepted that there was a significant difference between the groups. The Wilcoxon signed rank test was used to examine differences between intragroup time-dependent measurement values. If P < 0.05, the measurement values were considered to differ according to time.

RESULTS
A total of 50 patients were included in the study, and no patients were excluded from the study (Figure 1). The demographic and surgical data of the two groups were similar to each other ( Table 1).
Intraoperative remifentanil consumption was significantly lower in the ESP group (P < 0.01). Similarly, morphine consumption and rescue analgesic (meperidine) requirement over the first postoperative 24 hours were much lower in the ESP group (P < 0.01) ( Table 2).
Considering the presence of dynamic pain, this was observed in all the patients in the control group at the 10 th minute, while it was only observed in 16% of the patients in the ESP group (P = 0.000).
While dynamic pain was present in 88% of the control group at the 1 st hour, it was present in 24% of the ESP group (P = 0.000).
There was no significant difference in the presence of dynamic pain at the other times evaluated ( Table 3).
Evaluation of postoperative nausea-vomiting showed that this was present in all patients in the control group, and it was severe in 40%. On the other hand, 24% of the patients in the ESP group did not have nausea-vomiting (Figure 3). It was discovered that an average of 7.36 ± 0.9 dermatome levels (minimum 6, maximum 9) were blocked in patients who had ESP block ( Table 4).

DISCUSSION
There is still a debate about what constitutes effective and safe postoperative analgesia in hepatectomy surgery. In open-technique hepatectomies, postoperative pain arises from the surgical incision or diaphragmatic irritation, or it is of visceral origin. 10 In ERAS protocols, regional effective methods have been recommended for analgesia, postoperative mobilization and recovery after hepatectomy. 2 Use of iv opioids seems to be the most important part of multimodal analgesia in hepatectomy surgery. 3 However, there is an increasing tendency towards reducing morphine consumption, due to its toxic, immunological and oncogenic effects on the liver, although this is a controversial movement. 11    Although debate continues regarding the visceral effectiveness of the block, we predicted that bilateral ESP block from the lower thoracic region could contribute to postoperative analgesia in hepatectomy surgery, as observed in the cadaver studies. 5,13,14 We applied the block before making the surgical incision since this would reduce the effect of neuromodulation and improve postoperative pain control. 15 Considering that the mean duration of surgery was 216.2 ± 38.2 minutes in the ESP block group, we assume that the main effect of the block was on intraoperative remifentanil consumption. Thus, while the consumption of remifentanil was 3.2 ± 0.9 mg in patients who had ESP block, it was 4.6 ± 1.1 mg in the control group. In the postoperative period, it was found that NRS and DNRS scores and morphine and rescue analgesic consumption were significantly lower in the ESP block group, in all    showing an anti-inflammatory effect. 18 There has only been limited use of adjuvant in ESP block in clinical studies in the literature that were conducted to assess postoperative pain. 8,19 In our study, the NRS and DNRS scores, which were high in the first hours in the ESP group, were found to gradually decrease over other timeframes. Although we did not have a control group without dexamethasone for evidence, we think that the emergence of the anti-inflammatory properties of dexamethasone and the rescue analgesics used had an effect on this result. For this reason, we think that different randomized studies should be conducted to support our study, in order to specify the effect of dexamethasone. Furthermore, we investigated the effect of the block in the first postoperative 24 hours.
We are of the opinion that it should be investigated whether adjuvant-enhanced ESP block without catheter insertion has an effect on postoperative pain for more than 24 hours.
In the literature, there are two randomized studies investigating the effectiveness of ESP block in hepatectomy surgery. 8,9 In both studies, ESP block was found to reduce the intraoperative remifentanil consumption. Thus, we think that these results provide confirmation of the visceral analgesic property of the block. Kang et al. 9 used an ESP block at T8 bilaterally with 20 ml of 0.5% ropivacaine and compared this with use of 400 mcg of intrathecal morphine, in live liver donors who underwent laparoscopic hepatectomy.
The pain scores in patients who underwent ESP block were higher than in those who received intrathecal morphine, but they were within acceptable limits, and postoperative nausea was found to be similar to what we saw in our study. In the study of Kang et al.,9 multimodal analgesia was administered using a large number of agents, and long-term follow-up such as after 72 hours postoperatively was performed. The pain score in the first 24 hours was 1.3 in the intrathecal morphine group, while it was 2.5 in the ESP group.
In our study, the resting NRS score was determined as 1.9 for the ESP group at the 24 th hour, whereas the DNRS score was found to be 4.0 for the ESP group. We attribute our higher dynamic pain score to the open technique that was applied for the surgery, the use of retractors and the limited range of analgesics that we used, especially our use of non-steroidal anti-inflammatory drugs (NSAIDs).
Our aim in performing the block at T8 was to relieve the patients' painful breathing, caused by upper abdominal pain that resulted from retraction, and thus to reduce both the dynamic and resting pain scores, which was also successful. However, the difference in the presence of dynamic pain was found to disappear after the first hour. Additionally, although the NRS scores in the ESP group were lower than those in the control group, an average score of 4.1 was detected in the first hours.
Considering the duration of surgery, the postoperative anal- In the meta-analysis by Kendall et al., 20 it was reported that one of the most significant effects of ESP block was on postoperative nausea-vomiting, and that this resulted from both the decrease in opioid consumption and the high analgesic efficiency of the block.
In our study, postoperative opioid consumption was observed to be significantly lower in the ESP block group. While no nausea-vomiting was encountered in 24% of the patients who underwent the block, 44% had mild and 32% moderate nausea and vomiting.
In the control group, on the other hand, nausea and vomiting were observed, and 40% of the cases were severe. We think that we significantly reduced postoperative nausea-vomiting through decreasing morphine consumption over the first 24 hours and through increasing analgesic efficacy with the ESP block.
Our study had some limitations. The methodology was planned in a single-blind manner, which may have affected the objectivity of the results. Another factor with a possible effect on the outcome criteria was that patient homogenization could not be achieved.
To fully explain the true analgesic effectiveness of the ESP block, we formed the control group from patients who received systemic analgesics alone. However, lack of a block group without dexamethasone may have prevented us from evaluating the net effect of the adjuvant drug. In addition, dexamethasone, which was used as an adjuvant in the block, had a systemic analgesic effect as well as prolonging the duration of the block. Non-administration of intravenous dexamethasone to the control group may have affected the objective evaluation of analgesic efficacy between the groups. Another limitation was that the data were limited to a short period of time, for such a major surgery. We did not have a chance to determine the duration of the positive effect of the block that we performed.
In this study, we administered opioid alone over the first 24 hours, while avoiding NSAIDs and paracetamol because of their hepatotoxic effects, considering that they might have negative effects on the bleeding profile. This can be considered to be another limitation. Much lower NRS and DNRS scores could have been obtained through using analgesics with different effect mechanisms. We preferred to use a concentrated rate of 0.375% in the bilateral block.
Our preoperative application of the block may have caused the signs of local anesthesia toxicity to be masked through general anesthesia. This may have prevented us from objectively assessing the reliability of the bilaterally applied block at this concentration.