Analgesic efficacy of preoperative ultrasound transversal abdominal plane block for open hysterectomy

Abstract Transversus abdominis plane (TAP) block is a promising technique in post-operative pain relief, following various types of surgeries with an incision on the anterio-lateral abdominal wall. Our randomized, prospective, control trial evaluates its peri-operative analgesic effectiveness for total abdominal hysterectomy (AH) via Pfannenstiel approach. Forty-six women, admitted for intervention, were randomized. A group with an application of bilateral, preincisional TAP block with ropivacaine (n = 23) versus a control group (n = 23) were formed. The post-operative pain relief for all the participants consisted of a mono-component, patient-controlled morphine analgesia. The amount of total 24 h morphine consumption and intraoperative fentanyl use was calculated. Pain at rest and in motion was assessed on a Verbal Numeric Scale (VNS). The incidence of post-operative nausea and vomiting was registered. TAP block with ropivacaine reduced the 24 h post-operative cumulative morphine requirements. The morphine consumption of the TAP block group (14.5 mg ± 4 mg) was statistically significantly lower than the control one (21.7 mg ± 6.8 mg). TAP block decreased the intraoperative use of fentanyl and the post-operative VNS scores at rest and in motion. The groups did not demonstrate any difference in the incidence of nausea and vomiting after surgery. TAP block was not associated with any complications. Our study showed that TAP block effectively leads to superior analgesia in patients undergoing total AH.


Introduction
Hysterectomy is one of the most frequent interventions done in women. In the University Hospital of Obstetrics and Gynecology 'Maichin Dom' in Sofia, Bulgaria this type of surgery can be achieved in several ways: abdominal (longitudinal or transversal incision of the anterio-lateral abdominal wall), laparoscopic, robotic-assisted and a vaginal one. The major part of hysterectomies in our Clinic is those with the abdominal approach. Patients who undergo such an intervention usually suffer significant pain. The most important source comes from the anterior abdominal wall and the visceral structures. Obtaining an adequate post-operative pain relief is crucial for normal re-convalescence and an early hospital discharge. The most common way to attain this goal is multimodal preventive analgesia [1]. Together with different parenteral medications used for pain alleviation, the peripheral nerve blockade plays a major role in achieving it [2].
The purpose of our study was to evaluate the effect of such a loco-regional technique -the ultrasound guided TAP block on the perioperative analgesia in patients undergoing abdominal hysterectomy (AH) via Phannenstiel approach. The nature of TAP block consists of a local anaesthetic (LA) injection in the fascial plane between the internal oblique and the transverse abdominal muscles. Thus, the afferent nociceptive innervation of the antero-lateral abdominal wall is blocked [3]. Studies have demonstrated that this technique leads to a better perioperative analgesia [4,5], decreases the use of analgesics and their side effects, protects the central nervous system from the process of 'central sensitization' , that is, prevents from the development of chronic pain [6,7].
The primary objective of our work was to compare the perioperative use of morphinics. The second objective was to evaluate and compare the post-operative pain scores and the incidence of opioid side effects in the survey groups. Our hypothesis was that adding ropivacaine in the transversus abdominis plane before surgery decreases the peri-operative need of opiates and produces a superior post-operative pain relief.

Ethics statement
An approval was obtained from the Hospital Ethics Committee. All the participants signed written informed consent forms.

Design
The study was designed as a single-center, prospective, randomised clinical trial, without blinding. It was carried out at the University Hospital of Obstetrics and Gynecology 'Maichin Dom' in Sofia, Bulgaria. Two groups were formed -one with an application of TAP block (the participants with an even consecutive number in the trial) and a control group that did not receive a local blockade (the participants with an odd consecutive number in the trial). By reason of medico-legal considerations, a placebo-controlled group was not formed. The demographic data form include age, body mass, height and Body Mass Index (BMI).

Participants: selection and description
The participants screened for inclusion in the analysis was women undergoing elective, total AH via a Pfannenstiel approach. All the interventions were performed by one and the same team, with an operative technique, according to the current hospital protocols. The patients were ASA physical status Grades I-III, aged 18-70 years. Exclusion criteria were age <18 years, BMI over 35, alcohol or medicine abuse, preoperative treatment with opioids or glucocorticoids, allergies towards LAs, the presence of a psychiatric disease, morphine intolerance, a history of major abdominal surgical intervention, incapability to use the device for patient-controlled analgesia (PCA).

Technical information
The day before surgery all the patients were familiarised with the Verbal Numeric Scale principles of pain evaluation (from 0 = absence of pain to 10 = very severe pain) and received instructions how to use the PCA device. Each participant received a standardised general anaesthesia. Midazolam (0.03 mg/kg i.v.) and fentanyl (1 and 2 μg/kg i.v.) were used for premedication. The induction was achieved with propofol 2-3 mg/kg. Oro-tracheal intubation was facilitated with 1 mg/kg suxamethonium chloride. The maintenance of anaesthesia was with sevoflurane. Its inspiratory fraction was adjusted so to obtain values in the range of 40-60 on the BIS (Bispectral index) monitor. The neuromuscular blocking agent was atracurium 0.02 mg/kg. A ToF (Train of Four) was used to assess the degree of curarisation. If the hearth rate or the mean arterial pressure increased their values more than 25% from the baseline, then a bolus of fentanyl 1 µg/kg was applied. Normothermia was preserved with a warmed air cover. Before the beginning of the surgery, a bilateral TAP block with ropivacaine 0.5% in a dose of 2.5 mg/kg (to a maximal total dose of 200 mg) was applied for the patients of the corresponding group. The calculated amount of ropivacaine 0.5% for each patient was diluted up to 40 mL with NaCl 0.9% (20 mL for the left and 20 mL for the right side). The needle insertion approach was a lateral one [8]. We used an ultrasound machine BENq T3300 with a linear probe (6-13 MHz) and a 0.7 × 80 mm echogenic needle Ultraplex (B. Braun ® ). Following a verification of the exact position of the needle tip, the calculated volume of LA was injected into the TAP on the left and the right body side ( Figure 1). The control group, as mentioned above, did not receive any local blockade. Ondansetron 4 mg i.v. was applied to all the participants at the end of the surgery like prevention from post-operative nausea and vomiting (PONV). Intraoperative fluid replacement was performed with 15 mL/kg/h, 0.9% intravenous saline solution. Before extubation, if any signs of residual curarisation were observed, atropin 0.01 mg/ kg + neostigmine 0.02 mg/kg were applied. At the admission in the intensive care unit, all the patients received a loading dose of 0.05 mg/kg intravenous morphine. A PCA medical device (Graseby PCA pump, model 3300, with placed CE mark showing it has passed a conformity assessment) was attached to every participant, with the following setting: bolus of morphine at demand − 1 mg, lockout time period − 10 min, without any dose-limit for 24 h. The pain was assessed at rest and in motion (knee flexion) on VNS at six different time moments -the admission in the ICU (0 h), at the 3rd, 6th, 12th and 24th postsurgical hour. Post-operative nausea and vomiting (PONV) were registered on a four-point categorical scale (0 = absence, 1 = mild, 2 = moderate and 3 = severe). At the 24th post-surgical hour, the PCA was disconnected and the total amount of morphine consumption was registered.

Data analysis
The primary endpoint was the total 24-h post-operative morphine consumption. Secondary endpoints were the results from VNS pain scores at rest and in motion, nausea and vomiting. The sample size was determined as described earlier in a study on the effect of TAP block on post-operative analgesia after total AH, where the mean 24-hmorphine consumption was 23 ± 7 mg [7]. In the present study, a 25% decrease in absolute morphine consumption was considered clinically relevant. With α = 0.05 and β = 0.2, a minimum of 22 patients in each group were required.
Statistical analysis was performed with the IBM SPSS Statistics 19 (www.IBM.com). An independent samples t-test was used for continuous variables and the values were presented as means with standard deviations (±SD). To evaluate the normality of distribution, the Shapiro-Wilk test was used. The nonparametric data were analysed by descriptive statistics and the values were presented as medians and interquartile range. A Mann-Whitney U-test was performed to determine the level of significance. Two-way mixed ANOVA stat. test was applied to evaluate the repeated measurements. Differences were considered statistically significant at the p < 0.05 level.

Results
In this study, 55 women were assessed for eligibility in the trial and all of them were enrolled in the study. For different reasons, five patients in the TAP block group and four in the control one dropped out. Overall, 46 patients completed the study and were analysed ( Figure 2).
No statistically significant differences were observed between the two groups in terms of age, weight, height, BMI, ASA grade and the time of surgery ( Table 1).
The mean cumulative consumption of morphine for the first 24 post-operative hours was higher in the control group, 21.7 mg (SD ± 6.8 mg), than in the TAP block group, 14.5 mg (SD ± 4 mg). A statistically significant difference of 7.2 mg ± 1.7 mg (95% CI, −10.53 to −3.82), t (35.77) = −4.34, p = 0 was observed. The difference in the cumulative consumption of morphine on the 12th post-operative hour was also statistically significant ( Table 2).
The mean pain scores of the TAP block group, assessed on VNS, were lower than these of the control one. This trend was observed in all the time intervals for both static and dynamic pain (Figure 3). The difference in the mean values was statistically significant at all the time periods, that is, at the zero, 3rd, 6th, 12th and 24th post-operative hour. The only exception was the result of the 12th post-operative hour for dynamic pain (p = 0.441).
There was no statistical difference in the incidence of PONV between the groups. A Mann-Whitney U-test demonstrated medians equal to zero, U = 145, z= −1.488 and p = 0.137. No opioid-related side effects such as respiratory depression and urinary retention were observed.

Discussion
In our research, TAP block led to a decrease in post-operative morphine requirements in patients undergoing elective total AH via Pfannenstiel. The group that received the local blockade presented a reduced peri-operative consumption of opiates. TAP block provided a superior analgesia according to the pain scores at rest and in motion to a clinically relevant degree, but did not impact the incidence of PONV. No complications on account of this loco-regional technique were manifested in our study.
TAP block was described for the first time by Rafi [3,9]. He injected an LA in the fascial plane between the internal oblique and transversus abdominis muscles. Rafi used a blind, traditional landmark method, with an approach via 'Triangle of Petit' and a tactile sense of a 'pop' of the needle, when transfixing the fasciae of the abdominal wall. The entry of ultrasound in the fields of anaesthesiology allowed an easy  identification of the anatomical structures and a real-time visual control during the execution of the regional technique. In 2007, Hebbart et al. [10] described a performance of a TAP block using an ultrasound control.
Since then, different researchers have explored the benefits of TAP block, as a component of multimodal analgesia for post-operative pain relief, the following various surgical procedures such as colorectal operations [11], open appendectomy [12], retro-pubic prostatectomy [13], nephrectomy [14], inguinal hernia repair [15], laparoscopic cholecystectomy [16] and caesarean section [17]. TAP block has been used for treatment of chronic pain [18] and for analgesia amelioration in critically ill patients [19].
Several studies have evaluated the analgesic effectiveness of TAP block in patients undergoing total AH. Moyo et al. [20] made the conclusion that bilateral TAP block generates a statistically significant decrease in pain scores. Shin et al. [21] reported a significant decrease in the post-operative consumption of opiates and pain scores of the patients with TAP block. Røjskjaer et al. [22] studied 30 patients. According to their work, ultrasound-guided TAP block did not reduce the 24-h morphine consumption within a multimodal analgesic regimen, but did reduce the post-operative pain scores in the first post-operative hours [22]. Another survey, with 90 patients, concluded that pre-incisional TAP block decreases the intraoperative fentanyl requirements, prevents hemodynamic responses to surgical stimuli and provides an effective post-operative analgesia [23].
The controversial results still question the real efficacy of TAP block. Most researchers have evaluated its effect as a component of multimodal post-operative analgesia. To explore the potency of this peripheral technique, we designed a protocol with minimal influence of other analgesic drugs -a bilateral, preincisional TAP block in combination with a mono-component (morphine only), patient-controlled, post-operative analgesia. The obtained results indicated that TAP block can generate pain-relief after total AH via Pfannenstiel. Although this loco-regional blockade affects primarily the somatic pain of the anterio-lateral abdominal wall, some authors take into consideration its potency in visceral pain relief. They explain that with the relatively slow vascular resorption of the LA in the TAP and its direct penetration throughout the  abdominal transversal muscle into the peritoneal space. Thus a local blockade of the peritoneal nociceptors is achieved [24]. The application of 2.5 mg/kg ropivacain in the TAP demonstrates a safe and stable LA plasma concentration. The signs of LA systemic toxicity reactions are uncommon [25]. The assessment of the intraoperative efficacy of the TAP block is still a challenge. It is difficult to quantify the real nociception level, that is, the sufficiency of analgesia during the intraoperative period. Though we observed the depth of anaesthesia with a BIS monitor, the degree of neuromuscular blockade with a ToF stimulation and the intraoperative hemodynamic parameters, these methods are still unreliable. We were unable to make an interactive pain evaluation during general anaesthesia. Future studies with the implementation of the new systems for real-time nociception determination such as skin conductance, pupillometric assessment, Surgical Pleth Index, ANI (Analgesia Nociception Index) or NOL (nociception level) index should be carried out [26]. Our study has a few limitations. It was not blinded. There was no placebo group, only a control one. There were no dispositive to evaluate the degree of intraoperative pain.

Conclusions
Preincisional, ultrasound-guided TAP block decreased the intraoperative fentanyl requirements, post-operative morphine consumption and provided an effective post-operative analgesia. It is a safe and reasonably effective option to improve the patient's comfort after AH.