WITHDRAWN: Combination of ultrasound-guided pectoral nerve block I (PECS I) and serratus anterior plane block (SAP) for attenuation of surgical stress response during modified radical mastectomy: a prospective interventional randomized controlled trial

doi:10.21203/rs.3.rs-4665884/v1

Background and Aims

General anesthesia with multimodal analgesia is the standard anesthetic management during modified radical mastectomy. In this study, a combined ultrasound-guided pectoral nerve block (PECS I) and serratus anterior plane block (SAP) were used for surgical stress response attenuation and postoperative analgesia.

Methods

Thirty-six consenting patients were randomized into two groups. After induction of general anesthesia, Group B patients received ultrasound-guided PECS I and SAP block whereas Group C patients received intravenous analgesics only. Intraoperative fentanyl dosage to keep the systolic blood pressure (SBP) and heart rate (HR) within 20% of baseline was the primary outcome variable. Secondary outcome variables were intraoperative vitals, postoperative pain score, analgesic requirement, and nausea and vomiting. Wilcoxon rank-sum test (non-parametric data), Student's t-test (parametric data), and Chi-square test (categorical data) were used for comparison. P value <0.05 was considered statistically significant.

Results

Surgical stress response attenuation was achieved with a lower dosage of fentanyl in Group B compared to Group C [intraoperative fentanyl (mean±SD), 116.11±25.70 µg vs. 134.44±20.07 µg, P = 0.023]. Compared to Group C, intraoperative reduction in SBP and HR was higher in Group B [SBP reduction (mean±SD), 24.03±12.5 mm of Hg vs. 15.2±13.05 mm of Hg, P = 0.045 and HR reduction (mean±SD), 18.61±6.6 beats/min vs. 10.73±10.03 beats/min, P = 0.009 respectively]. The apparently higher pain scores in the control group were statistically insignificant.

Conclusion

A combined PECS I and SAP block attenuates intraoperative autonomic stress response due to the surgical stimulus with significantly less opioid requirement.

Trial Registration: CTRI/2023/03/050487. This trial is registered with the Clinical Trial Registry of India ON 09/03/2023. https://ctri.nic.in/Clinicaltrials/login.php

Breast Cancer

Modified Radical Mastectomy

Regional Anaesthesia

Modified radical mastectomy is a commonly performed breast cancer surgery where the removal of the whole breast and pectoralis major fascia along with complete axillary clearance is performed. ^[1–2] The mode of anesthesia administered during this procedure is general anesthesia along with a multimodal form of analgesia. The efficacy of fascial plane blocks like pectoral nerve block (PECS) ^[3–5], serratus anterior plane block (SAP) ^[6–7], and erector spinae plane block has been proven in previous studies. ^[8–9] Regional blocks as an adjunct to multimodal analgesia have been proven to attenuate the autonomic response to surgical stimulation and thus reduce opioid requirements in patients undergoing modified radical mastectomy. PECS I blocks the pectoral nerves which supply the pectoral muscles including the fascia covering the pectoralis major muscle. ^[10–11] During the SAP block, local anesthetic is deposited either superficial or deep to the serratus anterior muscle and causes dermatomal paraesthesia of the anterolateral chest wall from T2-T9. ^[12] Hence the combined PECS I and SAP block can be effective in reducing the surgical stress response during modified radical mastectomy.

The aim of the study was to assess the efficacy of a combined PECS I and SAP block as compared to an intravenous multimodal analgesic regime in attenuating surgical stress response and postoperative analgesia in cases posted for a post-chemotherapy modified radical mastectomy with complete axillary clearance. The primary objective was to estimate the intraoperative fentanyl requirement to reduce autonomic response due to surgical stimulus. The intraoperative vitals, postoperative numeric rating scale (NRS) pain score, postoperative analgesic use in the recovery room, and incidence of postoperative nausea vomiting (PONV) were the secondary objectives.

After obtaining approval from the institutional ethics committee, this prospective interventional single-blinded randomized controlled trial was registered with the Clinical Trial Registry of India. The study was conducted on 36 American Society of Anesthesiologists (ASA) I-II female patients between 18–65 years who underwent post-chemotherapy unilateral modified radical mastectomy with complete axillary clearance. The exclusion criteria were patient refusal and patient unable to give valid consent, patient undergoing supraclavicular lymph node dissection, pregnant patients, known hypersensitivity to local anesthetics, infection at the site of injection, and history of chronic analgesic use. After obtaining written informed consent, the patients were recruited between the time periods from 24th March 2023 to 30th May 2023. The study complied with the principles of the Helsinki Declaration 2013 and good clinical practices were followed.

Consenting patients were randomized into two groups with the help of a computer-generated randomization chart - the block group (Group B) and the control group (Group C). Baseline vitals were noted in the preoperative holding area.

A similar anesthesia protocol was followed for each patient. Inside the operating room after securing the intravenous access standard ASA monitors were attached. General anesthesia was induced using fentanyl 2 µg/kg, propofol 2 mg/kg, and atracurium 0.5 mg/kg intravenously (IV). The airway was secured using I-gel™ (Intersurgical Ltd, Wokingham, UK). Post-induction all patients received Dexamethasone 6 mg IV. Anaesthesia was maintained using sevoflurane, 50% nitrous oxide in oxygen, and 0.1 mg/kg boluses of atracurium. Patients were ventilated to maintain normocapnia. The minimum alveolar concentration (MAC) was maintained within the range of 0.8–1.3 to ensure adequate depth of anesthesia. Intraoperative vitals and MAC were noted at 3 min intervals. Intravenous fentanyl 0.5 µg/kg was administered if systolic blood pressure and heart rate increased to ≥ 20% of the basal values.

For patients enrolled in Group B, the blocks were provided after induction of general anesthesia. The patient’s position was supine with the arm abducted at 90°. After skin preparation with 2.5% chlorhexidine in alcohol, to identify the targeted planes, a high-frequency (6–11 MHz) linear array ultrasound transducer (M7 PremiumTM, Mindray) was used. For PECS I, the transducer was placed medial to the coracoid process in a parasagittal orientation. In the deltopectoral groove, the axillary vessels were identified above the second rib. The probe was further moved inferiorly and laterally until the third rib was encountered. The fascial plane between the pectoralis major and pectoralis minor was identified at the level of the third rib. A 20G echogenic needle was inserted from the cephalad end to reach the fascial plane. After negative aspiration, 10 ml of 0.25% bupivacaine was administered. For SAP block transducer was placed on the midaxillary line at the nipple level. The fifth and sixth ribs were identified with the pleura sliding underneath. The serratus anterior muscle lies immediately over the ribs. The needle was inserted from the anterior aspect towards the posterior direction. After negative aspiration, 25 ml of 0.25% bupivacaine was injected deep to the serratus anterior muscle.

Patients in group C did not receive any block and received only intravenous analgesics.

All patients received paracetamol 1gm and tramadol 100 mg IV prior to surgical incision. Prior to reversal, all patients received ondansetron 6 mg IV. Once the procedure was over patients were shifted to the recovery room where the NRS scores were noted at 0, 30, 60, 90, and 120 min. Any analgesic requirement (in the form of intravenous diclofenac sodium 75 mg IV or fentanyl 0.5 µg/kg bolus) during this time period and incidence of PONV were noted. Metoclopramide 10 mg IV was administered if found necessary. Patients were shifted to the ward after 2 h with a routine analgesic prescription.

The sample size was calculated using the online sample size calculator of OpenEpi (Open Source Epidemiologic Statistics for Public Health). ^[13] In a similar study conducted by Wang W et al. ^[14] it has been found that in patients who were administered a combination of PECS I and SAP block, intraoperative IV morphine equivalent consumption (mg) was significantly lower than the patients who did not receive any block [(mean ± SD) 18.10 ± 4.76 and 21.22 ± 4.17 respectively]. Morphine equivalents are optimal for opioid utilization studies as they facilitate both interpretation and comparison between opioids across geographical locations. Morphine equivalent is expressed as milligrams of morphine and is used to standardize the opioid dosage across different drugs and studies. ^[15] Hence we utilized the difference in morphine equivalents reported by the study for our sample size calculation. ^[14]

All analyses were done using R Statistical Software version 4.3.0 (2023-04-21). To test the normal distribution of the continuous data the Shapiro–Wilk test was used. Comparison between the two groups was done using the Wilcoxon rank-sum test (non-normally distributed continuous data and ordinal data) or a two-tailed Student's t-test (normally distributed continuous data). The Chi-square test was used to assess the categorical data. A P value of < 0.05 was considered statistically significant for all comparisons between the groups.

Forty-one patients were assessed for eligibility among whom four patients were fulfilling the exclusion criteria and one patient refused to participate. Hence thirty-six patients were recruited for the study. All of them complied with the study protocol and the data was put up for final analysis [Figure 1]. Demographic parameters were similar in both groups. The baseline diastolic and mean blood pressure of Group B patients were higher and found to be statistically significant. However, those values were clinically insignificant [Table 1].

Table 1

Demographic parameters and patient characteristics
Variables	Group B (n = 18)	Group C (n = 18)	P value
Age (years)	45.89 ± 6.82	45.61 ± 11.62	0.931
Weight (kg)	58.44 ± 12.34	63.17 ± 8.77	0.196
BMI (kg/m²)	25.75 ± 5.22	27.29 ± 3.55	0.309
ASA status % (I/II)	22.2/77.8	5.6/94.4	0.148
Baseline SBP (mm of Hg)	133.94 ± 10.99	127.67 ± 12.61	0.120
Baseline DBP (mm of Hg)	83.72 ± 5.20	78.44 ± 8.48	0.032
Baseline MBP (mm of Hg)	101.09 ± 6.26	95.00 ± 8.94	0.024
Baseline HR (beats/min)	92.22 ± 9.94	87.67 ± 10.04	0.180
Values are in mean ± SD and percentage (%) of patients. ASA - American Society of Anesthesiologists, SBP - Systolic blood pressure, DBP - Diastolic blood pressure, MBP - Mean blood pressure, HR - Heart rate

The intraoperative fentanyl requirement and perioperative fentanyl requirement (total fentanyl received intraoperatively and during the 2 h stay in the recovery room) were significantly lesser in patients who received a combination of PECS I and SAP block [intraoperative fentanyl (mean ± SD) 116.11 ± 25.70 vs. 134.44 ± 20.07, P = 0.023 and perioperative fentanyl (median, IQR) 120, 102.5–145 vs. 150, 132.5-173.75, P = 0.009] [Figure 2].

Attenuation of stress response due to the surgical stimulus was achieved with a significantly lower dosage of intravenous fentanyl and equivalent anesthetic depth (MAC were similar in both groups) in Group B patients. The intraoperative vitals were well controlled with a decrease in blood pressure and heart rate. Compared to Group C, intraoperative reduction in systolic blood pressure and heart rate was significantly higher in Group B [Table 2].

Table 2

Intraoperative hemodynamic parameters
	Group B (n = 18)	Group C (n = 18)	P value
Intraoperative reduction of SBP from baseline (mm of Hg)	24.03 ± 12.5	15.2 ± 13.05	0.045
Intraoperative reduction of DBP from baseline (mm of Hg)	8.10(4.42–18.32)	6.06(3.59–11.99)	0.355
Intraoperative reduction of MBP from baseline (mm of Hg)	16.7 ± 9.63	12.15 ± 9.9	0.171
Intraoperative reduction of HR from baseline (beats/min)	18.61 ± 6.6	10.73 ± 10.03	0.009
Values are in mean ± SD and median with IQR. SBP - Systolic blood pressure, DBP - Diastolic blood pressure, MBP - Mean blood pressure, HR - Heart rate

Though apparently higher pain scores were noted in the control group [Figure 3] those were found to be statistically insignificant [Table 3].

Table 3

Intraoperative and postoperative parameters
Variables	Group B (n = 18)	Group C (n = 18)	P value
Intraoperative SBP (mm of Hg)	111.20 ± 14.60	112.50 ± 10.91	0.764
Intraoperative DBP (mm of Hg)	72.76 ± 8.25	70.87 ± 8.92	0.514
Intraoperative MBP (mm of Hg)	84.42 ± 10.02	83.32 ± 8.93	0.732
Intraoperative HR (mm of Hg)	73.59 ± 8.52	75.33 ± 8.58	0.546
Minimum alveolar concentration (MAC)	1.02 ± 0.08	1.01 ± 0.10	0.888
Duration of Surgery (min)	104.33 ± 36.53	116.17 ± 34.83	0.327
NRS score at 0 min	2(0–2)	1.5(0-2.75)	0.869
NRS score at 30 min	2.5(2–4)	2.5(2-5.75)	0.605
NRS score at 60 min	2(2–3)	2(2–5)	0.193
NRS score at 90 min	2(1–2)	2(1.25-4)	0.159
NRS score at 120 min	2(1–2)	2(1.25-2)	0.817
Diclofenac in recovery room % (yes/no)	50/50	55.6/44.4	0.739
Fentanyl in recovery room (µg)	0(0–0)	0(0-46.25)	0.105
PONV % (yes/no)	27.8/72.2	27.8/72.2	1.000
Values are in mean ± SD, median with IQR, and percentage (%) of patients. SBP - Systolic blood pressure, DBP - Diastolic blood pressure, MBP - Mean blood pressure, HR - Heart rate, NRS - Numeric Rating Scale, PONV - Postoperative nausea and vomiting

Intraoperative vitals, minimum alveolar concentration (MAC), duration of surgery, and incidence of PONV were similar in both groups [Table 3].

A combination of PECS I and SAP block can effectively attenuate the intraoperative surgical stress response as evidenced by significantly lower intraoperative fentanyl requirement to maintain stable vitals. In both groups, intraoperative vitals were well controlled, and the reduction in systolic blood pressure and heart rate was significantly greater in the block group with the equivalent anesthetic requirements. Hence greater attenuation of the stress response is achievable with blocks without using incremental dosages of opioids.

Though in a previous study by Wang W et al., the visual analog score was lower in the block group, this study has shown similar pain scores in both groups. However, the intraoperative fentanyl requirement was higher in the control group in our study which is similar to the findings of Wang W et al. ^[14] The higher dosage of fentanyl along with pre-incision intravenous tramadol, paracetamol, and dexamethasone administration had led to equivalent pain control in Group C patients. Postoperatively, in all patients, we used intravenous diclofenac initially and fentanyl thereafter whenever the pain score was ≥ 4. Hence it can be concluded that a multimodal form of analgesia effectively reduces pain without causing significant PONV when blocks are not administered albeit with higher dose of opioids.

In PECS I, local anesthetic is injected in the fascial plane between the pectoralis major and pectoralis minor muscles and it targets the lateral (C5-7) and medial (C8-T1) pectoral nerves. ^[10–11] These are the major nerves supplying the pectoral muscles including fascia covering the pectoralis major muscle. Hence PECS I can effectively block the pain arising from the dissection of the pectoralis major fascia and lymphadenectomy at various levels around the pectoralis minor muscle. In PECS II in addition to PECS I a second injection is made at the level of the fourth rib between the pectoralis minor and serratus anterior muscle. This second injection blocks the lateral cutaneous branches of upper intercostal nerves (T2–T6) causing dermatomal anesthesia to the anterolateral chest wall and also the long thoracic nerve (C5–C7), which is the motor supply of the serratus anterior muscle. ^[10] During the SAP block, dermatomal paraesthesia of the anterolateral chest wall from T2-T9 is achieved by injecting local anesthetic either superficial or deep to the serratus anterior muscle. ^[12] Hence both PECS II and SAP block can effectively block the anterolateral chest wall. Previous studies also suggest similar results. ^[16–19]

PECS II/serratus blocks utilize the same mechanism which is blocking the lateral branches of the upper intercostal nerves. Hence their efficacy is related to their ability to reach the specific fascial plane ^[20]. In the midaxillary line, the serratus plane is superficial and easier to identify during ultrasonography, making it a much simpler block compared to PECS II ^[12]. Hence the combination of PECS I and SAP block is easier to perform and it provides adequate surgical stress response reduction and postoperative analgesia in patients posted for a post-chemotherapy modified radical mastectomy with complete axillary clearance.

A smaller sample size could be the limitation of this study. In this study, we have included only ASA I and II patients. The blocks could be effective in attenuating autonomic responses in poorly controlled hypertensive cancer patients where surgery is time-sensitive. Further studies on such patients are required to conclude the same.

A combined PECS I and SAP block attenuates intraoperative autonomic stress response due to the surgical stimulus with a lower opioid requirement. A multimodal form of analgesia is effective in reducing pain without causing significant PONV when blocks are not administered.

Consent for publication: Not applicable

Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have no competing interests

Funding: Nil

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Plesca M, Bordea C, El Houcheimi B, Ichim E, Blidaru A. Evolution of radical mastectomy for breast cancer. J Med Life. 2016;9:183.
Bland KI, Chang HR, Copeland EM III. Modified radical mastectomy and simple mastectomy. InThe breast 2018 Jan 1 (pp. 443–61). Elsevier.
Senapathi TG, Widnyana IM, Aribawa IG, Jaya AG, Junaedi IM. Combined ultrasound-guided Pecs II block and general anaesthesia are effective for reducing pain from modified radical mastectomy. J Pain Res. 2019;12:1353.
Bashandy GM, Abbas DN. Pectoral nerves I and II blocks in multimodal analgesia for breast cancer surgery: a randomized clinical trial. Reg Anesth Pain Med. 2015;40(1):68–74.
Thomas M, Philip FA, Mathew AP, Krishna KJ. Intraoperative pectoral nerve block (Pec) for breast cancer surgery: A randomized controlled trial. J Anaesthesiol Clin Pharmacol. 2018;34(3):318–23.
Jain D, Mohan VK, Bhoi D, Batra RK, Kashyap L, Shende D, et al. Analgesic efficacy and spread of local anesthetic in ultrasound-guided paravertebral, pectoralis II, and serratus anterior plane block for breast surgeries: A randomized controlled trial. Saudi J Anaesth. 2020;14(4):464.
Arora S, Ovung R, Bharti N, Yaddanapudi S, Singh G. Efficacy of serratus anterior plane block versus thoracic paravertebral block for postoperative analgesia after breast cancer surgery-a randomized trial. Brazilian J Anesthesiology. 2022;72:587–92.
Leong RW, Tan ES, Wong SN, Tan KH, Liu CW. Efficacy of erector spinae plane block for analgesia in breast surgery: a systematic review and meta-analysis. Anaesthesia. 2021;76(3):404–13.
Zhang Y, Liu T, Zhou Y, Yu Y, Chen G. Analgesic efficacy and safety of erector spinae plane block in breast cancer surgery: a systematic review and meta-analysis. BMC Anesthesiol. 2021;21:1–2.
Blanco R, Fajardo M, Maldonado TP. Ultrasound description of Pecs II (modified Pecs I): a novel approach to breast surgery. Rev Esp Anestesiol Reanim. 2012;59(9):470–5.
Sun Q, Liu S, Wu H, Kang W, Dong S, Cui Y, Pan Z, Liu K. Clinical analgesic efficacy of pectoral nerve block in patients undergoing breast cancer surgery: a systematic review and meta-analysis. Medicine. 2020;99(14):e19614.
Blanco R, Parras T, McDonnell JG, Prats-Galino A. Serratus plane block: a novel ultrasound‐guided thoracic wall nerve block. Anaesthesia. 2013;68(11):1107–13.
Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version 3.01. www.OpenEpi.com, updated 2013/04/06, accessed 2022/12/01. https://www.openepi.com/Menu/OE_Menu.htm.
Wang W, Song W, Yang C, Sun Q, Chen H, Zhang L, et al. Ultrasound-guided pectoral nerve block I and serratus-intercostal plane block alleviate postoperative pain in patients undergoing modified radical mastectomy. Pain Physician. 2019;22(4):E315.
Nielsen S, Degenhardt L, Hoban B, Gisev N. A synthesis of oral morphine equivalents (OME) for opioid utilisation studies. Pharmacoepidemiol Drug Saf. 2016;25(6):733–7.
Chin KJ. Thoracic wall blocks: From paravertebral to retrolaminar to serratus to erector spinae and back again–A review of evidence. Best Pract Res Clin Anaesthesiol. 2019;33(1):67–77.
Kelava M, Alfirevic A, Bustamante S, Hargrave J, Marciniak D. Regional anesthesia in cardiac surgery: an overview of fascial plane chest wall blocks. Anesth Analgesia. 2020;131(1):127–35.
Sharma R, Louie A, Thai CP, Dizdarevic A. Chest wall nerve blocks for cardiothoracic, breast surgery, and rib-related pain. Curr Pain Headache Rep. 2022;26(1):43–56.
Chin KJ, Versyck B, Pawa A. Ultrasound-guided fascial plane blocks of the chest wall: a state‐of‐the‐art review. Anaesthesia. 2021;76:110–26.
Franco CD, Inozemtsev K. Refining a great idea: the consolidation of PecS I, PecS II and serratus blocks into a single thoracic fascial plane block, the sap block. Reg Anesth Pain Med. 2020;45(2):151–4.

No competing interests reported.

WITHDRAWN: Combination of ultrasound-guided pectoral nerve block I (PECS I) and serratus anterior plane block (SAP) for attenuation of surgical stress response during modified radical mastectomy: a prospective interventional randomized controlled trial

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Editorial Note

Abstract

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Introduction

Methods

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

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