Comparative evaluation of superficial and deep serratus anterior plane block for postoperative analgesia following modified radical mastectomy: a randomised controlled study

BACKGROUND AND RATIONALE

Breast cancer has continued to be the most common cancer affecting women. It has overtaken lung cancer as the most commonly diagnosed malignancy and is the leading cause of cancer-related death in women.[1,2]

Modified radical mastectomy (MRM) is a common surgical procedure, accounting for 31% of all breast cancer surgery cases performed. Postmastectomy pain managed by opioids alone often leads to side effects such as nausea and vomiting. Inadequate control of pain may later develop into chronic pain syndrome (paraesthesias, phantom breast pain and intercostobrachial neuralgia) in 25%–40% of the patients. Despite that the breast cancer age-standardized mortality rates have decreased by 2%–4% per year since the 1990s,[3] the incidence of breast cancer was 11.7% in total new cases in 2020, both sexes and in all ages.[4] Breast cancer treatment methods include surgery, radiotherapy, chemotherapy, hormone therapy, targeted therapy, and immunotherapy.[5] Surgery is the only possible cure for breast cancer, so surgical resection of the tumor is the preferred treatment for early breast cancer.[6,7]

The incidence of acute postoperative pain (APP) is high in breast cancer surgery, and opioids are the most commonly used drugs to treat APP. However, they are not without systemic side effects, which may increase comorbidities.

There are some local or regional nerve blocks in breast cancer performed as core components of multimodal analgesia and enhanced recovery after surgery (ERAS), including thoracic epidural, interscalene brachial plexus, paravertebral, pectoral nerve blocks, and erector spinae plane block.

Thoracic Epidural Block in combination with the administration of opioids has been widely regarded as the gold standard for thoracic analgesia. Paravertebral Block is a technique which involves injection of local anesthetic into the paravertebral space to block nerves after they exit the spinal cord.

The nerve block usage is increasing in popularity as it decreases pain as estimated by visual analogue scores/numerical rating pain scores postoperatively and decreases the need for postoperative narcotic analgesic usage thereby reducing opioid induced side effects like postoperative respiratory depression, nausea, vomiting, NSAID induced gastritis etc. Nerve blocks also shorten Post-Anaesthesia Care Unit stay time, and also increases patient satisfaction. They also cause less interference with the physiology of our body as they act by interrupting the nociceptive impulse transmission through the peripheral nerves. The use of ultrasound guidance for performance of peripheral nerve blocks increases the success rate, reduces block performance times, improves quality of block, reduces the local anaesthetic doses needed and reduces the chances of complications.

Serratus anterior plane (SAP) block is an interfascial block which blocks the lateral branches of intercostal nerves providing analgesia for breast and thoracic surgeries. In some studies, the serratus anterior block has shown to cause chest wall analgesia lasting for 12 hours following breast surgery.Ultrasound-guided serratus anterior plane block (SAPB) is a new analgesic technique proposed by Blanco; it is a block in which local anesthetic is deposited within an interfascial plane either superficial or deep into the serratus anterior muscle at the mid-axillary line.[8,9] A preliminary study by Blanco et al. had shown that the deposition of local anaesthetic solution superficial to serratus anterior muscle is associated with long lasting analgesia compared to the injection deep to the muscle. On the other hand, in a study by Fajardo et al.,it was postulated that the space between serratus anterior muscle and external intercostal muscle is less distensible, resulting in wider drug spread with respiratory movements aiding in drug dispersion.[10]

Abdallah et al. reported that both superficial and deep SAPB provided effective blockade to alleviate the pain after modified radical mastectomy for breast cancer, however, this study is prone to bias because of its design and non-randomisation.[11] Edwards et al.[12] suggested that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB but this study had a significant heterogeneity in the patients included as they included both unilateral and bilateral surgeries, mastectomies with or without axillary clearance and different volumes of local anaesthetic were used.

 We hypothesise that the deep SAPB would provide better postoperative analgesia following modified radical mastectomy than the superficial SAPB.

So, this study has been planned to compare the superficial and deep serratus anterior plane block for postoperative analgesia following modified radical mastectomy (MRM).

Rahimzadeh P  et al (2018) conducted a study of total of 60 patients who were candidates for mastectomy under general anaesthesia were divided in this trial into two groups. The first-experimental-group (SAB) underwent the ultrasound-guided serratus anterior block, but the second-control-group (CTL) received no block intervention. An intravenous patient-controlled analgesia (PCA) device was used to deliver fentanyl in both groups. Using the Visual Analog Scale (VAS), the patients’ pain was assessed at intervals of 1, 6, 12 and 24 hours after entering the recovery room. Intravenous acetaminophen was administered as a rescue analgesic if the pain exceeded 3 on the VAS. A total amount of fentanyl consumed, the time to first PCA request, a total amount of acetaminophen consumption and possible adverse effects were evaluated. The pain scores assessed at the time intervals were not significantly different between the two groups (p>0.05). The total consumption of fentanyl was significantly lower in the SAB group than in the CTL group (p=0.0001). Duration of the time to first PCA request was remarkably longer in the SAB group than in the CTL group (p=0.0001). The total amount of acetaminophen consumed was notably higher in the CTL group than in the SAB group (p=0.001). None of the patients experienced side effects. Undertaking serratus anterior block following mastectomy can reduce pain scores and lower opioid usage.

Abdallah FW  et al (2018) conducted a study in which one hundred sixty-six patients were propensity matched among 2 groups (83/group): superficial and deep serratus blocks. The cohort was used to evaluate the effect of blocks on postoperative oral morphine equivalent consumption and area under the curve for rest pain scores. They considered deep serratus block to be noninferior to superficial serratus block if it were noninferior for both outcomes, within 15 mg morphine and 4 cm·h units margins. Other outcomes included intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and incidence of postoperative nausea and vomiting.  Deep serratus block was associated with postoperative morphine consumption and pain scores area under the curve that were noninferior to those of the superficial serratus block. Intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and postoperative nausea and vomiting were not different between blocks. The postoperative in-hospital analgesia associated with deep serratus block is as effective (within an acceptable margin) as superficial serratus block following ambulatory breast cancer surgery. These new findings are important to inform both current clinical practices and future prospective studies.

Gad M  et al (2019) conducted a study that patients were randomly allocated to three equal groups after induction of general anaesthesia. Levobupivacaine group (L) (n=50): received levobupivacaine 0.25% in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. Levobupivacaine–dexmedetomidine group (D) (n=50): received levobupivacaine of 0.25% plus 0.5 mcg/kg dexmedetomidine in a volume of 0.5 ml/kg injected superficial to serratus muscle between it and latissimus dorsi muscle. Group C (n=50), as a control group: received sham block with normal saline in a volume of 0.5 ml/kg. Time to first analgesia request and postoperative opioid consumption were the primary outcomes. This study demonstrated that addition of dexmedetomidine to levobupivacaine in ultrasound-guided serratus plain block during modified radical mastectomy surgery delayed time of first analgesia request and reduced postoperative opioid consumption compared with levobupivacaine alone. Hemodynamic changes (hypotension and low heart rate) and sedation were more pronounced in dexmedetomidine group than the other two groups. Occurrence of nausea and vomiting in dexmedetomidine group is lower than the other two groups. The addition of dexmedetomidine as an adjuvant to levobupivacaine in ultrasound-guided serratus plain block during modified radical mastectomy surgery can give extended analgesic effect and lower postoperative opioid consumption.

Edwards JT,  et al (2021) conducted a Randomized prospective trial  at academic hospital. Total 64 women, >18 years of age, ASA I-III, undergoing single or bilateral mastectomy, with and without lymph node biopsy, with and without tissue expander reconstruction. Either superficial or deep SAPB by an ultrasound-guided technique in addition to multimodal analgesia.  The primary outcome was opioid consumption in the first 24 h. Secondary outcomes were pain scores, satisfaction scores, incidence of PONV, length of stay and block performance time.  Subjects who received a deep SAPB required 30% less oral morphine equivalents (OME) (113.5 mg vs. 147 mg, p = 0.009) and reported lower pain scores. There were no significant differences in satisfaction scores, incidence of PONV, LOS, or block performance time between the two groups.  There was a significant difference in opioid consumption between the deep and superficial SAPB groups. Subjects in the deep SAPB group had lower pain scores at 12 h; however, the difference was not statistically significant at other time points. While both the superficial and the deep SAPB can be used for post-operative analgesia in patients undergoing mastectomy, our study suggests that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB as shown through decreased opioid consumption of 30% over a 24-h period post-block.

Bhoi D  et al (2022) conducted a study that total 40 female patients scheduled to undergo elective modified radical mastectomy under general anaesthesia (GA) were randomly assigned to receive ultrasound guided SAP block with 30 ml 0.375% ropivacaine either superficial (group S, n = 20) or deep (group D, n = 20) to the serratus anterior muscle, before the induction of GA. The primary outcome was post operative fentanyl requirement over 24 hours and secondary outcomes were comparison of numerical rating scale (NRS) scores for pain, sensory block mapping, time to perform the block, number of needle attempts, etc. The post operative 24-hour fentanyl requirement was comparable between group S and D (318.75 ± 80.65 versus 272.5 ± 80.25 μg, P = 0.07). NRS pain scores were comparable between the groups. Sensory block mapping done at various levels showed T3–T7 block in most of the patients with no difference between the groups. Block performance time (6.05 ± 3.27 versus 8.35 ± 3.26 minutes, P = 0.034) and number of needle attempts was significantly lesser in group D. There was no difference in analgesic efficacy when SAP block was given superficial or deep to serratus anterior muscle for modified radical mastectomies. However, deep SAP block required less time and number of attempts to perform than superficial technique.

 AIM AND OBJECTIVES

Comparative evaluation of superficial and deep serratus anterior plane block for postoperative analgesia following modified radical mastectomy (MRM) Primary Objective:

To compare the time to first rescue analgesia in two different techniques of SAP block

Secondary objectives:

To compare the following parameters between the two groups:

Total intraoperative opioid (fentanyl) consumption

Total postoperative opioid (tramadol) consumption in first 24 hours

Pain scores(Numerical rating scale) in post-operative period at 0,2,6,12,24 hours

Number of needle attempts

Block performance time

Patient satisfaction score

Post operative nausea and vomiting (PONV)

Any other complications.

MATERIAL AND METHODS

Study Setting: The study will be conducted in Department of Anaesthesiology, King George’s Medical University, Lucknow in collaboration with Department of Endocrine surgery, KGMU, Lucknow after getting clearance from the Ethical Committee, Research Cell, KGMU, Lucknow.

Study Design:     Prospective randomized controlled study

Study Duration: One year

Ethical Clerance: Applied for Ethics committee, Research Cell, KGMU, Lucknow

Sample size calculation: 80 cases (40 cases in each group)

On the basis of study by Bhoi et al,[13] the mean difference in duration to first rescue analgesia (in hours) in between superficial group (2.38) and deep group (2.83) was 0.45 and the average variance (σ2) was 1.36.The sample size (n) was calculated using the following formula, assuming 0.05 level significance (Zα/2 =1.96), and 80% power(Z [1-β]=0.84) :

 2 (Zα/2 + Z [1-β])2 × σ2

n =

(μ1�’μ2)2

 2 (1.96 + 0.84)2 ×1.362

n =

(2.83-2.38)2

 n=37.91

Considering the provision of data loss, we will enroll 40 patients in each group of the study.

Inclusion Criteria:

Patient giving consent

Age 18-60 years

ASA Grade I and II

scheduled for elective unilateral modified radical mastectomy for breast cancer

Exclusion Criteria:

History of allergy to any trial drugs, presence of coagulopathy or bleeding disorders

Infection at the nerve block site

Chest wall deformity

Body mass index more than or equal to 35kg/m2

Ingestion of any analgesic drug within 48 hours before surgery

History of chronic pain medication use

Trauma or history of thoracic spine surgery

Sinus bradycardia

Methodology:

After getting clearance from Institutional Ethical Committee, a total of 80 patients undergoing modified radical mastectomy, satisfying inclusion and exclusion criteria and giving written informed consent will be enrolled in this study. The participants will be randomly allocated to one of the two study groups using a computer-generated list of random numbers, randomly grouped on a scale of 1:1. On the day of surgery, the study administrator will hand over the envelope to the anesthesia assistant. The patients will be randomly assigned to one of the following two groups:

Group S (Superficial): Ultrasound-guided injection of 30 ml of 0.2 % Ropivacaine will be given above the serratus anterior muscle

Group D (Deep): Ultrasound-guided injection of 30 ml of 0.2% Ropivacaine will be given below the serratus anterior muscle

All enrolled patients will undergo a complete evaluation (history, physical examination, biochemical and haematological tests and 2D echocardiography, if history of neoadjuvant chemotherapy) and will be instructed regarding use of numerical rating scale (NRS) for pain on a scale of 0–10 (0 – no pain and 10 – worst possible pain). The patients will not be aware of the group they will be allocated. All patients will be premedicated with alprazolam 0.25 mg and pantoprazole 40 mg orally. All other medications being taken for concurrent medical illness will be continued.

The patients will be taken inside the operating room and standard monitors (electrocardiography, non-invasive blood pressure and pulse oximetry) will be attached. After recording baseline haemodynamic parameters, intravenous (IV) access will be secured and midazolam 1 mg IV will be administered. Induction of GA will be done with IV fentanyl 2 μg/kg and propofol in titrated doses (1.5–2.5 mg/kg) and vecuronium 0.08 mg/kg followed by Igel insertion. In both the groups SAP block will be performed after the induction of GA. A 22-gauge blunt tip, echogenic needle will be used for conduct of the SAP block. A linear high frequency (6–13 MHz) ultrasound (US) probe will be used for guidance of the block. All the blocks will be performed after the administration of general anaesthesia (GA) by two anaesthesiologists having experience in performing ultrasound guided SAP block.

The patient will be made to lie down in the supine position and skin sterilisation will be done with 2% chlorhexidine. The ultrasound probe will be placed over the mid-clavicular region of the thoracic cage in a sagittal plane and the ribs will be counted inferiorly and laterally, until the fifth rib in the midaxillary line will be identified .

The latissimus dorsi (superficial and posterior), teres major (superior) and serratus muscles (deep and inferior) will be identified by ultrasound, overlying the fifth rib. After subcutaneous infiltration with 2% lignocaine, the block needle will be inserted in the lateral to medial direction in an in-plane approach until the tip will be placed below the latissimus dorsi muscle and above the serratus anterior muscle in group S and deep to serratus anterior muscle in group D. 30 ml of 0.2% ropivacaine will be injected in the fascial plane after negative aspiration. The block performance time will be noted which will be measured from needle puncture to deposition of local anaesthetic. The number of changes of needle direction and attempts will also be noted.. A separate anaesthesiologist who will be blinded to the group allocation will note the outcome parameters.

Anaesthesia will be maintained by sevoflurane with oxygen/air mixture and positive pressure ventilation. Fentanyl bolus of 20 μg will be given if the blood pressure or heart rate exceeds 20% of the baseline and the total intra-operative fentanyl consumption will be recorded. Injection paracetamol 1 gm and ondansetron 0.1 mg/kg will be given IV 30 minutes before the end of surgery. The total surgical duration will be noted. After the conclusion of surgery, neostigmine (50 μg/kg) with glycopyrrolate (10 μg/kg) will be given when the patient demonstrates spontaneous respiratory efforts. The Igel will be removed and the patients will be transferred to the post anaesthetic care unit (PACU) for monitoring vitals, pain assessment and providing analgesia. First pain assessment will be done as soon as the patient will be awake, oriented and capable of following commands and subsequently at 2, 6, 12, 24 hours at both rest and the movement of the ipsilateral arm.. Injection tramadol 100 mg IV bolus will be given whenever patient complains of pain and having NRS ≥4 and the time to first rescue analgesia will be recorded. There should be a gap of 6 hours between the doses and the total dose in 24 hours should not exceed 4gm. All patients will be encouraged to ambulate and resume oral intake early. Injection paracetamol 1 gram will be given 6 hourly to all patients. Ondansetron 0.1 mg/kg will be repeated 8-hourly in the post operative period. The number of episodes of PONV will be recorded and rescue anti-emetic treatment will be provided with ondansetron 4 mg IV. Total postoperative opioid consumption in the first 24 hours will be noted. All the patients will be asked about their satisfaction score on a scale of 0–4 (0 – not satisfied; 4 – fully satisfied).

Statistical Analysis

All statistical analyses will be performed using IBM SPSS software Version.23.0 (IBM, Armonk, NY: IBM Corp). The normality of quantitative variableswill be examined with the Kolmogorov–Smirnov test. Quantitative variables will be expressed as mean or median (IQR). Student’s t-test will be used to compare the mean values of age, weight, height, operation time, and PACU discharge time.. In addition, analysis of variance will be performed on multiple comparisons to assess pain scores within 24 hours after surgery. A p-value <0.05 will be considered statistically significant in the two-sided test.

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