Pectoral nerve block1 versus modified pectoral nerve block2 for postoperative pain relief in patients undergoing modified radical mastectomy: a randomized clinical trial

      Abstract

      Background

      Pectoral nerve block1 (PEC1) given between pectoralis major and minor, and modified pectoral nerve block2 (mPEC2) performed between pectoralis minor and serratus anterior, can provide continuous analgesia after modified radical mastectomy (MRM) when catheters are placed before skin closure. This study was designed to compare PEC1 and mPEC2 block for providing postoperative pain relief after MRM.

      Methods

      Sixty-two physically fit patients undergoing MRM were assigned into two groups (Group PEC1, n=31 and Group mPEC2, n=31). Before wound closure, epidural catheter was placed in the group designated muscle plane and 30ml of 0.25% bupivacaine was injected through the catheter after wound closure. Bupivacaine 15ml of 0.25% top up was given on patient's demand or whenever visual analogue scale (VAS) score was>4. Time for first analgesia (TFA), number of top ups and VAS was recorded at 0.5, 6, 12, 18, 24 h after surgery. Sensory blockade was assessed 30 min after extubation.

      Results

      Analgesia was significantly prolonged in group mPEC2 [mean(SD)] 313.45(43.05) vs 258.87(34.71) min in group PEC1, P<0.001. Total pain experienced over 24 h was significantly less in group mPEC2 [mean(SD)] 9.77(6.93) than in group PEC1 24.19(10.81), P<0.0001. Consequently, top up requirements were significantly reduced in group mPEC2 than in group PEC1 [median(range)] 3(2-4) vs 4(3-5) respectively, P<0.001. Lateral pectoral (77.42% and 35.48%) and thoracodorsal nerves (93.55% and 48.39%) had higher incidence of sensory block in group mPEC2 than group PEC1, P<0.001.

      Conclusions

      mPEC2 provides better postoperative analgesia than PEC1 when catheters are placed under direct vision after MRM.

      Clinical trial registration

      CTRI/2017/02/007811 (REF/2015/11/010185).

      Key words

      Editor's key points
      • Regional anaesthesia may have some benefits for managing acute pain after mastectomy.
      • It is unclear if different approaches to pectoral nerve block confer any analgesic advantage.
      • This study compared the analgesic efficacy of direct catheter placement between different muscle layers.
      • The modified PEC2 block provided better analgesia, with local anesthetic spread towards the axilla.
      Patients undergoing modified radical mastectomy (MRM) under general anaesthesia consume 6 to 48 mg of morphine,
      • Grover VK
      • Mathew PJ
      • Yaddanapudi S
      • Sehgal SA
      single dose of preoperative gabapentin for pain reduction and requirement of morphine after total mastectomy and axillary dissection: randomized placebo-controlled double-blind trial.
      • Kaya M
      • Oğuz G
      • Şenel G
      • Kadıoğulları N
      Postoperative analgesia after modified radical mastectomy: the efficacy of interscalene brachial plexus block.
      putting them at a risk of developing opioid induced side-effects.
      • Walder B
      • Schafer M
      • Henzi I
      • Tramer MR
      Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review.
      Pectoral nerve (PEC) blocks have been shown to provide satisfactory analgesia after breast surgery and decrease opioid consumption.
      • Blanco R
      The ‘pecs block’: a novel technique for providing analgesia after breast surgery.
      • Bashandy GM
      • Abbas DN
      Pectoral nerves I and II blocks in multimodal analgesia for breast cancer surgery: a randomized clinical trial.
      As the presence of a catheter in and around the surgical site can be a hindrance and undesirable, conventionally PEC blocks are performed preoperatively under ultrasound guidance, as “single-shot injections”
      • Pérez MF
      • Miguel JG
      • de la Torre PA
      A new approach to pectoralis block.
      • Leiman D
      • Barlow M
      • Carpin K
      • Piña EM
      • Casso D
      Medial and lateral pectoral nerve block with liposomal bupivacaine for the management of postsurgical pain after submuscular breast augmentation.
      • Chakraborty A
      • Khemka R
      • Datta T
      • Mitra S
      Combipecs, the single-injection technique of pectoral nerve blocks 1 and 2: a case series.
      with no provision to continue PEC block during the postoperative period. Hence different techniques of prolongation of the blocks, such as supplementing PEC block with other blocks
      • Ueshima H
      • Otake H
      • Asai T
      Addition of transversus thoracic muscle plane block to pectoral nerves block provides more effective perioperative pain relief than pectoral nerves block alone for breast cancer surgery.
      have been tried to prolong the duration of PECs block. Placing the catheter under direct vision
      • Haydon NB
      • van der Rijt R
      • Down C
      • Buckland G
      A novel technique of intraoperative lateral pectoral nerve block during subpectoral breast implant placement.
      • Hinchcliff KM
      • Hylton JR
      • Orbay H
      • Wong MS
      Intraoperative placement of pectoral nerve block catheters: description of a novel technique and review of the literature.
      before wound closure will ensure accuracy and provide a route to deliver continuous analgesia in the postoperative period.
      Conventionally in PEC1 block, injection is made between pectoralis major and minor muscles, while in PEC2 block in addition to PEC 1 block another injection is made between pectoralis minor and serratus anterior. As the anatomical compartments are breached after surgery, the technique of administering postsurgical PEC2 block without combining it with PEC1 has been termed by the authors as modified PEC2 (mPEC2) block.
      It has been demonstrated that PEC2 block provides better quality of analgesia than compared with PEC1 when given preoperatively.
      • Blanco R
      • Fajardo M
      • Parras Maldonado T
      Ultrasound description of pecs II (modified pecs I): a novel approach to breast surgery.
      However, it remains to be seen whether the disruption of interfascial planes after surgery will alter the spread of the local anaesthetic and efficacy of PEC1 and PEC2 blocks. This study was therefore designed to compare PEC1 and mPEC2 block (local anaesthetic injected between pectoralis minor and serratus anterior) as the modality for postoperative pain relief in patients undergoing modified radical mastectomy. The primary aim of the study was to compare analgesic efficacy of PEC1 and mPEC2 block in terms of time for first rescue analgesic, VAS score and number of top-ups in 24 h. The secondary aims were to map the spread of sensory block and to observe side-effects if any.

      Methods

      This double blinded, randomized, clinical trial was conducted after obtaining approval from the institutional ethical committee (Reg. No. ECR/62/Inst/WB/2013) dated 26/05/2015, and CTRI registration CTRI/2017/02/007811 [CTRI registration was applied in November 2015 (REF/2015/11/010185); final modifications were submitted in February 2016, CTRI registration number was confirmed on February 8th, 2017]. Sixty-two ASA grade I–II female patients in the age group of 35–65 yr, undergoing unilateral modified radical mastectomy under general anaesthesia, were recruited for the study after obtaining the written informed consent. Patients with history of hypertension, diabetes, known allergy to local anaesthetic, major cardiac disorders, renal dysfunction, pre-existing neurological deficits, and psychiatric illness were excluded in addition to patients who refused to participate in the study (two patients were excluded from initially recruited 64 patients). All patients were kept nil orally overnight and premedicated with oral alprazolam 0.25 mg and ranitidine 150 mg the night before and two h before surgery. During the preoperative visit, patient characteristics data was recorded and visual analog scale (VAS; 0–10, 0=no pain, 10=worst pain) was explained to the patients.
      Patients were randomly allocated into two groups (Group PEC1, n=31 and Group mPEC2, n=31) using computer-generated random numbers (Fig. 1). The group allocation numbers were concealed in sealed opaque envelopes that were opened after enrollment of the patients. The catheter was placed between pectoralis major and minor in Group PEC1 and between pectoralis minor and serratus anterior in Group mPEC2 before wound closure under direct vision by the operating surgeon (Fig. 2).
      Figure thumbnail gr1
      Fig 1Consort flow chart. Group PEC1: general anaesthesia and PEC1, Group mPEC2: general anaesthesia and mPEC2.
      Figure thumbnail gr2
      Fig 2Epidural catheter being positioned between muscle planes after surgery under direct vision before wound closure. (A) PEC1 Block (Catheter placed between pectoralis major and pectoralis minor). (B) mPEC2 Block (Catheter placed between pectoralis minor and serratus anterior).
      In the operating room, 18-gauge i.v. cannula was cited on the opposite side and baseline ECG, heart rate (HR), non-invasive blood pressure (NIBP), and peripheral oxygen saturation (SpO2) were recorded using a multiparameter monitor. General anaesthesia was induced with i.v. fentanyl 1 µg kg−1 followed by propofol 1.5–2 mg kg−1 i.v. until loss of verbal response. Tracheal intubation was facilitated with atracurium 0.5 mg kg−1 and anaesthesia was maintained with isoflurane (minimal alveolar concentration 1–1.3) and 66% nitrous oxide in 33% oxygen through a circle system. Patient's lungs were ventilated with positive pressure ventilation to maintain end-tidal carbon dioxide between 4.0 and 4.5 kPa. ECG, NIBP, SpO2, end tidal carbon dioxide and nasopharyngeal temperature were continuously monitored and recorded throughout surgery. All patients received a continuous infusion of ringer lactate solution at the rate of 5–8 ml kg−1 h−1 during surgery. Fentanyl 25 µg was given i.v. if mean bp or heart rate exceeded 20% of the preoperative value. Any incidence of hypotension (mean arterial pressure<65 mm Hg) was treated with rapid infusion of 200 ml ringer lactate and, if required, injection mephentermine was given in 3 mg i.v. boluses. Bradycardia (HR < 50 beats min−1) was treated with i.v. atropine (0.6 mg). All the patients received ondansetron 0.1 mg kg−1 i.v. over 20 min before completion of surgery. At the end of surgery before wound closure, a perforation was made with 18 gauge Tuohy needle (B. Braun, Germany: Perifix® one 401 filter set) just below clavicle and an epidural catheter was passed through it. The surgeon placed the catheter with the tip directed towards axilla, either between pectoralis major and minor muscle (Group PEC1), or between pectoralis minor and serratus anterior (Group mPEC2). Once the skin closure was completed, 30 ml of 0.25% bupivacaine was injected through the catheter under complete aseptic conditions and surgical drains were kept clamped for 15 min before making the injection. Residual neuromuscular block was antagonized with the mixture of neostigmine (2.5 mg) and glycopyrrolate (0.4 mg) i.v. and tracheal extubation was performed when the patient was fully awake.
      In the postoperative recovery room pain intensity was measured with VAS score at 0.5 h, six, 12, 18, 24 h postoperatively. At 30 min, postoperatively sensory block was assessed for lateral pectoral, median pectoral, intercostals, thoracodorsal and long thoracic nerves with pin prick method in their area of distribution, barring the area of surgical incision. Time for first analgesic top up (primary outcome measure of the study) was noted when the VAS reached>4 or if the patient demanded analgesia. Each top up comprised of 15 ml of 0.25% bupivacaine and the number of top ups required in 24 h were noted in all patients. If the pain relief was inadequate after a top up dose (VAS score>4), rescue analgesia with 100 mg of i.v. tramadol was provided. All data was recorded by an investigator who was blinded to the group allocation and was not involved or present during surgery.

      Statistical analysis

      Sample size for the study was calculated on the basis of time to first rescue analgesia as the primary outcome measure. It is estimated that 31 subjects will be required per group in order to detect a difference of 33 mins in this parameter with 80% power and 5% probability of Type I Error. This calculation assumed a SD of 46 mins on the basis of an initial pilot study in 10 subjects (5 in each group) and two-sided testing. As the only intervention was placement of catheter in group designated muscle plane, no dropouts were anticipated in the study and therefore no adjustment to sample size was made. Statistical analysis was carried out by entering raw data into MS Excel and analysed using IBM SPSS® statistical package version 20 (SPSS Inc., Chicago, IL, USA). Patient characteristics and clinical data from the two groups were compared using two-tailed Student's t-tests. Intergroup differences between VAS over time recorded throughout the 24-h period were analysed by Friedman's Test, as the VAS for Group mPEC2 was not normally distributed, and Mann-Whitney U-test was performed to determine the significance for area under the curve, P<0.001. Median bupivacaine top up doses were analysed using Mann-Whitney U-test and sensory block was analysed by using Fisher's exact test. P<0.05 was considered statistically significant for all tests.

      Results

      The physical characteristics and the duration of surgery were comparable in both the groups. Baseline mean arterial pressure and intraoperative mean fentanyl requirements were similar in both the groups. (Table 1).
      Table 1Patient characteristics and baseline parameters in both the groups. Values expressed as mean (SD) for the number of patients in each group. *Age expressed as mean (range) for the number of patients in each group
      ParametersGroup PEC1 (n=31)Group mPEC2 (n=31)
      Age (yr)*48.9 (38–60)49.8 (38–62)
      Height (cm)157.35 (4.62)157.97 (4.45)
      Weight (kg)60.45 (6.14)60.19 (6.52)
      BMI (kg/m2)24.44 (2.52)24.19 (2.99)
      Duration of surgery (min)119.1 (9.15)121.9 (8.31)
      Baseline mean arterial pressure (mm Hg)93.35 (9.16)96 (9.15)
      Intraoperative fentanyl consumption (µg)34.68 (12.38)32.26 (11.54)
      Satisfactory pain relief (mean VAS score<2.5) was observed in both the groups throughout the study period. However, a comparison of total pain experienced over 24 h (area under the VAS pain vs time curve) was significantly lower in group mPEC2 (mean 9.77, SD 6.93) when compared with group PEC1 (mean 24.19, SD 10.81), P<0.0001 (Fig. 3). Similarly, VAS pain score in group mPEC2 was significantly less at 6, 12, 18 and 24 h postoperatively when compared with group PEC, P<0.05 (Fig. 3). Duration of analgesia was significantly prolonged in group mPEC2 (mean 313.45, SD 43.05 min) when compared with group PEC1 (mean 258.87 SD 34.71 min), P<0.001. Consequently, significantly lesser number of top up doses of bupivacaine were received in group mPEC2 (median 3, range 2–4) when compared with group PEC1 (median 4, range 3–5), P<0.001. None of the patients in both the groups required any rescue analgesic dose or had any complications.
      Figure thumbnail gr3
      Fig 3Mean VAS (SEM) over time in both the groups. VAS=Visual Analogue Scale, SEM=Standard error of mean. Area under curve for Group mPEC2 [9.77 (6.93)] [mean(SEM)]. Area under curve for Group PEC1 [24.19 (10.81)] [mean(SEM)]. *P<0.05.
      Sensory block of lateral pectoral and thoracodorsal nerves was more frequently demonstrated in group mPEC2 (77.42% and 93.55%) when compared with group PEC1 (35.48% and 48.39%), P<0.01 (Table 2).
      Table 2Percentage of patients having sensory block in both the groups. *P<0.05
      NervesGroup PEC1 (n=31)Group mPEC2 (n=31)P value
      Lateral pectoral nerve35.4877.42*0.002
      Medial pectoral nerve96.7790.320.301
      Intercostal nerves (III-VI)1001001.000
      Long thoracic nerve93.55100.00.151
      Thoracodorsal nerve48.3993.55*<0.001

      Discussion

      We have demonstrated that both PEC1 and mPEC2 provide a good quality of postoperative pain relief, when catheters are placed under direct vision before wound closure in patients undergoing MRM. However, mPEC2 provided significantly better quality and long duration of pain relief than PEC1. When regional blocks are not used, postoperative morphine consumption can range anywhere between 6–48 mg during the first 24 h after MRM.
      • Blanco R
      The ‘pecs block’: a novel technique for providing analgesia after breast surgery.
      • Blanco R
      • Fajardo M
      • Parras Maldonado T
      Ultrasound description of pecs II (modified pecs I): a novel approach to breast surgery.
      The annual audit (2014–2015) of our institution revealed mean morphine consumption of 20.5 mg during first 24 h postoperatively, in patients undergoing MRM when regional blocks were not used during or after general anaesthesia for providing postoperative pain relief.
      PEC1 block is performed between pectoralis major and minor muscle resulting in blockade of lateral pectoral nerve (C5-7) and medial pectoral nerve (C8-T1), hence it is more useful in superficial breast surgery such as breast augmentation.
      • Blanco R
      The ‘pecs block’: a novel technique for providing analgesia after breast surgery.
      • Desroches J
      • Grabs U
      • Grabs D
      Selective ultrasound-guided pectoral nerve targeting in breast augmentation: how to spare the brachial plexus cords?.
      On the other hand PEC2 block is more complete and blocks most of the nerve supply of the breast (pectoral, intercostobrachial, third to sixth intercostals, and the long thoracic and thoracodorsal nerves) and is therefore more suitable for major cancer surgery of the breast involving axillary dissection. As an additional separate injection was not made between pectoralis major and minor muscles as in PEC2 block, the technique was termed as modified PEC2 (mPEC2) block.
      In all the previous clinical trials, pectoralis blocks were given preoperatively under ultra-sonographic guidance and as a single shot technique.
      • Wahaba SS
      • Kamal SM
      Thoracic paravertebral block vs pectoral nerve block for analgesia after breast surgery.
      • Kulhari S
      • Bharti N
      • Bala I
      • Arora S
      • Singh G
      Efficacy of pectoral nerve block versus thoracic paravertebral block for postoperative analgesia after radical mastectomy: a randomized controlled trial.
      Hence putting a catheter preoperatively in the mentioned plane would have been cumbersome and a hindrance in the operating field. In the current study, pectoralis nerve blocks (PEC1 and mPEC2) were performed under direct vision after completion of surgery with an epidural catheter placed between two muscle planes. Hence, the benefit of these blocks could be extended into the postoperative period. However, anatomical compartments are breached after surgery and the injected drug does not confine itself into a particular interfascial compartment. Hence the spread of drug would be different from the conventional technique given with the fascial plane intact. Some proportion of the injected drug will have the tendency to gravitate down into the axilla and block the nerves in the planes below.
      Both PEC1 and mPEC2 blocks clinically provided satisfactory analgesia (VAS score was never>2.5 and none of the group required any rescue analgesic). Sensory block of lateral pectoral and thoracodorsal nerve was more frequently observed in patients belonging to group mPEC2, consequently these patients had better quality and longer duration of analgesia when compared with group PEC1. Sparing of lateral pectoral and thoracodorsal nerve in PEC1 block was also observed in the pilot study conducted to determine the sample size for the current study. After obtaining the informed consent from patients recruited for the pilot study, a drug mixture (1.5% methylene blue mixed with 30ml of the 0.25% bupivacaine) was injected in the two groups in the respective muscle planes after wound closure, to observe the spread and stain pattern of the drug and dye mixture. Stay sutures were applied and after waiting for 10 min, sutures were removed to note dye spread and structures stained. In PEC1 block patients, the dye and LA mixture did not trickle down to the axilla as space between pectoralis major and minor muscle is large enough to contain major volume of injected drug mixture (Fig. 4). As a result, the lateral pectoral nerve is likely to be spared as it exists in different plane and the drug is unable to reach the nerve despite the disruption of interfascial planes. Whereas in mPEC2 block the space between pectoralis minor and serratus anterior is small and most of the drug mixture was seen to spill into the lateral wall of thoracic cavity and move upwards to the axillary fold to block the lateral and medial pectoral nerve. The thoracodorsal nerve is located more laterally (it was partially stained in the pilot study) and is likely to be partially blocked with PEC1 than in case of mPEC2. intercostobrachial nerve is severed during surgery and leads to sensory loss of the supplied area.
      Figure thumbnail gr4
      Fig 4Pattern of spread and staining of structures after injection of bupivacaine and methylene blue mixture in PEC1 and mPEC2 block. (A) Figure shows the pattern of spread and staining in PEC1 block. The axillary folds are spared. Area of lateral pectoral nerve is not stained. Thoracodorsal nerve which is more lateral is partially stained. (B) Figure shows the pattern of spread and staining in mPEC2 block. Axilla is well stained with the dye as it has ascended up. (C) Figure shows the pattern of spread and staining in mPEC2 block. Area of lateral pectoral nerve and thoracodorsal nerve are well stained. P. minor=Pectrolis minor, LPN=Lateral pectoral nerve, TDN= Thoracodorsal nerve, LTN=Long thoracic nerve.
      Catheter dislodgement if not fixed to any underlying structure and blood collection might hamper the action and spread of local anaesthetics. The port sides of the drains and epidural catheters are different, hence each time the local anaesthetics were infiltrated, the surgical drains needed to be clamped for 15 min in order to give time for the local anaesthetics to act. Having a catheter in close vicinity of operated site raises a remote chance of infection. However, none of these potential complications were observed in the current study.
      To conclude, mPEC2 provides better quality and duration of postoperative analgesia than PEC1 when catheters are placed under direct vision after MRM. However, both PEC1 and mPEC2 blocks provide good quality of continuous analgesia.

      Authors’ contributions

      Study design/planning: S.G., P.K., J.B.
      Study conduct: S.G., J.B.
      Data analysis: P.K., J.B.
      Writing paper: S.G., P.K.
      Revising paper: all authors

      Declaration of interest

      None declared.

      Funding

      Study equipment and support was provided by institutional resources (Vivekananda Institute of Medical Sciences, Kolkata, India).

      Acknowledgements

      The authors would like to thank Soumya Maitra for his help in editing tables and figures; Dept. of Anaesthesiology and Critical Care, VIMS for their support in conducting this study; Dept. of Surgery, VIMS and specially Dr Suparna Ghosh for conducting Breast Clinic and for helping in administering the PEC blocks; Dr Avijit Hazra and Dr S Manikandanfor his help with statistical analysis.

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