Comparison of Quality of Recovery - 15 (QOR-15) in patients undergoing breast surgery for cancer following PECS block with Levobupivacaine and Ropivacaine- A Double Blinded, Randomized Controlled Trial

Introduction

According to WHO, Cancer is one of the largest healthcare burdens worldwide among all the diseases which is calculated as Disability-adjusted life years (DALYs)(1). Breast cancer is becoming increasingly the most common type of cancer worldwide surpassing the incidence of lung cancer. The data shows that over 2 million cases of breast cancer are reported worldwide(2). The incidence of breast cancer has increased in India.

The treatment and management of breast cancer depend on various factors like age, clinical condition, pain, and/or staging of the cancer. There are various modalities of management i.e. chemotherapy, radiotherapy, and surgical intervention, which are applied on a case-to-case basis.  The most common anesthesia that is preferred in breast surgeries is general anesthesia but some of the high-risk breast surgeries can be done via nerve block. The various surgical options breast-conserving therapy (BCT; often called lumpectomy) and axillary node dissection or a modified radical mastectomy (MRM), which includes removal of all breast tissue as well as the axillary lymph nodes (3). Modified radical mastectomy (MRM), is associated with considerable acute postoperative pain and restricted shoulder mobility. MRM is a common surgical procedure, accounting for 31% of all breast surgery cases performed. Post-mastectomy pain managed by opioids alone often leads to side effects such as nausea and vomiting(4). The acute postoperative pain can develop into chronic pain if it is not managed adequately. Hence, it is most important to have an effective method/plan to manage the acute post-operative plan(5).

Reported estimates of the incidence of persistent pain after mastectomy vary widely, with some studies finding incidence rates as high as 50%. Several risk factors have been suggested, including severe preoperative pain, severe acute postoperative pain, surgical factors such as the number of lymph nodes removed and the complexity of the surgery, prior or concurrent radiotherapy or chemotherapy, obesity, depression or anxiety, and age.(6)

The inadequate management of acute postoperative pain also leads to delay in recovery, delayed discharge from the hospital, impaired respiratory and immune functions, and increased risk of complications associated with the stay inside the hospital like ileus, thromboembolic manifestations, infections, and increased cost.5 Post-operative pain, stress and use of morphine have been elucidated as factors responsible for increased risk of metastasis.Inadequate control of pain may later develop into chronic pain syndrome (paraesthesias, phantom breast pain and intercostobrachial neuralgia) in 25%–40% of the patients(7).

There are various regional blocks that are given for analgesia in these patients like the PECS block, thoracic paravertebral block, intercostal blocks, and lately the erector spinae block. Ideally, a thoracic paravertebral block is the best for managing postoperative pain. Regional infiltration of anaesthetic agents resulted in improved analgesia, decreased perioperative morbidity and shorter hospital stays(8). For these reasons, regional analgesic techniques have been advocated for effective pain management. Local wound infiltration is safe, but the duration of action is short lived. Intercostal nerve block and interpleural block are effective, but there is a risk of pneumothorax and transient Horner’s syndrome. In view of the neurological and haemodynamic concerns, thoracic epidural analgesia is not preferred for breast surgeries.

The ultrasound-guided PECS I block, with the advantages of simplicity and ease of performance, is the type of regional nerve block that blocks the neuronal transmission of medial and lateral pectoral nerves via injecting a local anesthetic between pectoralis major and minor muscle. Pectoral nerve (PECS) block is a new technique for providing surgical anaesthesia and postoperative analgesia during breast surgery that relies upon the placement of local anaesthetic between the thoracic wall musclesand is therefore devoid of major adverse effects. The PECS I block is a superficial block that has been used effectively for surgical procedures such as placement of breast expanders and subpectoral prosthesis, shoulder surgery with deltopectoral groove involvement, and insertion of a pacemaker or intercostal drain(9).

PECS II block is a modified version of the same in which the local anesthetic is injected between the pectoralis minor and serratus anterior muscle.(10) The PECS II block favours mastectomy and axillary clearance, as it blocks the long thoracic nerve and lateral branches of the intercostal nerves from T3 to T6 in addition. This has shown a statistically significant decrease in VAS pain score postoperatively and decreased requirement of analgesics like tramadol, fentanyl, etc. The limited duration of action that is provided by the regional nerve block has warranted the use of various drug combinations to have prolonged and effective pain management(11).

Levobupivacaine is an amino-amide local anesthetic. It inhibits nerve transmission by blocking the voltage-gated sodium channels on the cell membrane. It blocks nerve conduction in sensory and motor nerves(12).

Ropivacaine is a long-acting amide local anesthetic. It exhibits a similar mechanism of action to other local anesthetics in that it reversibly inhibits sodium ion influx in nerve fibers. Amides preferentially bind and inactivate sodium channels in the open state—thereby blocking the propagation of action potentials. Ropivacaine is less lipophilic than other local anesthetics, such as bupivacaine, and is less likely to penetrate large myelinated motor fibers. It, therefore, selectively acts on the nociceptive A, B, and C fibers over the AB (motor) fibers. Ropivacaine is also manufactured as a pure S(-) enantiomer; the S(-) enantiomer has significantly less cardiotoxicity and neurotoxicity(13).

We Deng et al. evaluated the effect of three different concentrations of same volume Ropivacaine in PECS block. PECS block was given along with general anesthesia in three different groups with 0.2%, 0.3% and 0.4%. The postoperative analgesic effect was evaluated with numerical rating scale (NRS) pain score. They found that a dose of 0.3% ropivacaine was the optimal concentration for a PECS II block for patients undergoing MRM because it provided effective analgesia during and more than 48 hours after MRM. They also postulated that increasing the concentration thereafter didn’t improve the analgesia significantly(14).

The recovery after surgery is a complex process, usually observed through conventional indicators, and depends on various factors. The quality of the recovery-15 questionnaire is an important test to quantify the early post-op health status. QoR-15 questionnaire is a standardized and established questionnaire to understand the quality of recovery.  The quality of recovery (QoR-15) was specially designed to assess psychometric and functional recovery from the patient’s perspective.(15) The QoR-15, a validated instrument developed by Stark et al., encompasses various dimensions of postoperative recovery, providing a comprehensive evaluation beyond conventional pain scores. Its multifaceted approach includes assessments of pain, physical comfort, emotional state, and overall patient satisfaction, offering a holistic perspective on the recovery process(15).

Peter A. Stark et al.,(2013) (15) conducted a study aimed at developing a short-form postoperative QoR score and tested its validity, reliability, responsiveness, and clinical acceptability and feasibility. Based on extensive clinical and research experience with the 40-item QoR-40, the strongest psychometrically performing items from each of the five dimensions of the QoR-40 were selected to create a short-form version, the QoR-15. This was then evaluated in 127 adult patients after general anesthesia and surgery. There was good convergent validity between the QoR-15 and a global QoR visual analog scale (r = 0.68, P < 0.0005). It was concluded that the QoR-15 provides a valid, extensive, and yet efficient evaluation of postoperative QoR(16).

Marcin et. al. evaluated the quality of recovery in three group of patients undergoing breast surgery i.e. erector spinae block (ESP) group (0.375% ropivacaine), SHAM group (0.4 ml/kg 0.9% saline) and control group (CON). They assessed the QoR-40 score postoperatively along with VAS score, 24-hour opioid consumption with patient controlled analgesia (PCA) pump etc. to evaluate the analgesic effect of the block. They found that compared to the control group, the ESP block improved the QoR, alleviated pain intensity, and lowered opiod consumption in patients undergoing breast surgery(17). They also noted that patients in the CON group used PCA sooner than those in the ESP group and participants in the ESP group were more satisfied with treatment than those in the CON group. They also found no statistical difference between SHAM and the other groups.

Hammad et. Al. showed that erector spinal block and PECS both can be used efficaciously for providing analgesia in modified radical mastectomy for breast cancer. PECS block with 20ml 0.25% Bupivacaine showed significant better outcomes compared with Erector spinae block and control group on quality of recovery (QoR-40) score. Mean VAS scores were also lower in PECS block group. However, PECS shows better outcomes(18).

The comparison of quality of recovery with PECS block in patients undergoing breast surgery has never been studied. The results of this study may have implications for broader anesthesia practice, guiding clinicians in tailoring regional anesthesia regimens to individual patient needs. Ultimately, such advancements in perioperative care have the potential to improve the overall recovery experience for patients undergoing breast surgery for cancer, fostering enhanced well-being and improved postoperative outcomes.

Review of Literature

The pectoral nerve (PECS) blocks I and II are a novel technique that is employed in cases of thoracic surgeries, most commonly in breast surgeries to relieve post-operative pain. It relies upon the placement of local anaesthetic between the thoracic wall muscles and is therefore devoid of major adverse effects. It blocks the nerve transmission from intercostal nerves 3 to 6, pectoral nerves, and long thoracic nerves.

The pectoral nerve block was first used in minor breast surgery by Blanco et al. in 2011 (19) in which a large volume of local anesthetic was injected in between the interfascial plane of the pectoralis major and pectoralis minor muscle to block the nerve transmission from lateral pectoral nerves. PEC II block is aims to block the pectoral, the intercostobrachial, the intercostals III and VI, and the long thoracic nerves. These nerves need to be blocked to provide complete analgesia during breast surgery. The PECS II block is generally safe. Minor complications may include intravascular injection in the acromiothoracic artery and cephalic vein, and pneumothorax.

In 2012, Blanco et al.(10) described a modified version of this block after injecting an additional dose of local anesthesia in between the pectoralis minor and serratus anterior muscle and blocking the transmission from intercostal nerves 2 to 6, inter-costobrachial and long thoracic nerves, all these are necessary for axillary lymph node dissection. He also concluded that pectoral block decreases the requirement of postoperative analgesics. The study observed that the PEC block provides better pain relief compared with the paravertebral and reduces postoperative opioid consumption.

Mohammad et al, (20) aimed to compare prospectively the quality of analgesia after modified radical mastectomy surgery using general anesthesia and Pecs blocks versus general anesthesia alone. The study concluded that combined Pecs I and II block is a simple, easy-to-learn technique that produces good analgesia for radical breast surgery. He also demonstrated that the combination of PECS I and II block led to a more pronounced reduction in post-operative pain in radical breast surgery and showed that it was much easier and simpler to learn the technique.

Garg R et al.(21) have evaluated the efficacy of fascial plane blocks as alternate modes of analgesia in breast surgeries in female patients undergoing breast surgeries. It was found that the PEC 1 and PEC 2 block had minimum complications and residual effect such as persistent hypotension and can be used in day care surgeries. He also observed that no single block effectively covers the whole of the breast and axilla. He concluded that a combination of blocks may be used to have effective postoperative pain management and have minimum complications and side effects.

S. Kulhari et. al.(9)also reported that the PECS II block provided superior postoperative analgesia than the transthoracic paravertebral nerve block in patients undergoing modified radical mastectomy without causing any adverse effect. Whereas Kamiya et. al.(22) also assessed that the PECS block improved the postoperative pain after PECS block in breast surgeries but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain.

Kim D et al(23) evaluated the analgesic efficacy of PECS II block in patients undergoing breast-conserving surgery (BCS) and sentinel lymph node biopsy (SNB). (The control group did not receive any regional analgesia). It was observed that PECS II block reduced pain intensity and opioid requirements for 24 hours in patients who underwent the surgery.23

Nair G et al.,(2021) (24) performed a single-center prospective, observational cohort study of patients undergoing elective breast procedures (both cancer and non-cancer surgery) on regional anesthesia techniques that may improve patient recovery beyond treating postoperative pain alone and may facilitate patients in their return to functional, psychological as well as emotional baselines. They hypothesized that the quality of recovery (QoR) experienced by patients following breast surgery was associated with the type of anesthesia received as well as the use of a regional anesthesia technique during surgery. One hundred patients completed baseline QoR-15 questionnaires before surgery, of which 96 also completed QoR-15 questionnaires on postoperative day 1. It was concluded that breast surgery patients receiving PVB or a combination of regional blocks during surgery have higher postoperative QoR-15 scores, after adjustment for other factors.

Alberto et al(25)studied the use of Pectoralis Blocks in Breast Surgery and concluded that among patients undergoing breast-conserving surgery, PECS blocks moderately reduce postoperative opioid use, prolong time to analgesic rescue, and decrease postoperative pain scores when compared with systemic analgesics.

Alka et al. (26) assessed the Quality of recovery (QoR-15) following the administration of intravenous (IV) lignocaine or IV fentanyl in patients undergoing septoplasty surgery. They concluded that both improved postop QoR-15 scores. It is a standardized score that is commonly used to assess the quality of recovery following various surgeries. In a similar study by Surrender (27) et. al, they utilized an extensive version of the quality of recovery- 40 scores to assess the postoperative recovery after administration of IV lignocaine vs IV dexamethasone in patients undergoing laparoscopy cholecystectomy.

Patient Controlled Analgesia:

PCA implies an intermittent and on demand delivery of IV opioids by the patient itself with or without a background infusion. This is facilitated by a microprocessor driven infusion pump which delivers a predetermined dose of the opioid when the patient presses the demand button according to his/her needs. This prevents the analgesic gaps in post-operative period as it maintains a constant drug level in the plasma. PCA is based on a negative feedback loop mechanism, has a facility of lock out interval, and even the maximum amount of the drug that a patient can take in a certain period is entered in the program of the PCA pump. These inherent features of PCA prevent overdosing of the patients and are safe in clinical practice(28).

Lacunae in the existing literature

Limited studies have been published so far to compare the quality of recovery of these two drugs within the established technique of anesthesia like PECS block for breast surgery. In conclusion, studying these drugs is still relatively new and requires further evaluation, and it may have a place in perioperative pain management for the appropriate cases. Hence, this study has been planned to compare Levobupivacaine versus Ropivacaine in the PECS block in breast surgeries.