What Is the Role of Locoregional Anesthesia in Breast Surgery?

A Systematic Literature Review Focused on Pain Intensity, Opioid Consumption, Adverse Events, and Patient Satisfaction

Pasquale Sansone; Luca Gregorio Giaccari; Mario Faenza; Pasquale Di Costanzo; Sara Izzo; Caterina Aurilio; Francesco Coppolino; Maria Beatrice Passavanti; Vincenzo Pota; Maria Caterina Pace

Disclosures

BMC Anesthesiol. 2020;20(290)

Discussion

Our systematic review is the first to demonstrate the analgesic benefits of locoregional anesthesia following breast surgery, and to demonstrate the clinical utility of these techniques. For perioperative and postoperative analgesia, locoregional anaesthesia can be used as a standalone anaesthetic technique, or in association with sedation or general anaesthesia. In almost all the studies of this review, locoregional anesthesia was performed to reduce pain as an "adjuvant technique".

Lumpectomy/Mastectomy

Pain Intensity. Pain intensity on a numeric rating scale (NRS) was lower in the intervention group than in the placebo group at 1, 6, 12, 24 and 48 h after surgery. The difference of NRS at 1 h between the groups was statistically significant (p = 0.02); no statically significant difference was reported at other intervals.

In the first hour after surgery, all patients in the intervention group reported NRS lower than 4; instead in the placebo group, two studies (Ferreira Laso et al., 2014; Wang et al., 2018) experienced, respectively, a mean pain intensity of 6.7 and 4.3. In the placebo group we also found NRS higher than 4 in Wang et al 2019 after 6 h and in Ferreira Laso et al 2014 after 24 h.

We considered NRS lower than 4 as an optimal cut-off point between mild and moderate pain. This cut-off was identified as the tolerable pain threshold.^[29]

Opioid Consumption. Postoperative use of opioids was lower in the interventional group both upon discharge from the PACU and after 48 h, although there was no statistically significant difference. The difference in opioid use was statistically significant in three studies (Ferreira Laso et al., 2014; Ilfeld et al., 2014; Versyck et al. 2017) at the time of discharge from the PACU. Eight studies (Campbell et al., 2014;^[10] Ferreira Laso et al., 2014; Gürkan et al., 2018; Mohamed et al., 2013; Neethu et al., 2018; Versyck et al. 2017; Wang et al., 2018; Yao et al., 2019) reached statistical significance after 48 h from surgery.

Safety. No statistically significant difference was noticed (p = 0.74) between interventional and placebo groups. Among the intervention group a total of 163 AEs was reported. Nausea, vomiting or PONV were the most common (59%), followed by bruising (14%), haematoma/bleeding (6%), seroma (6%), pruritus (4%) and haemodynamic alterations (4%), such as hypotension, hypertension or bradycardia.

Patient Satisfaction. Patient satisfaction was high, with minimum 92% of satisfaction among patients treated with locoregional anesthesia. The satisfaction rate was also high in the placebo group (79%).

Breast Augmentation

Pain intensity on a numeric rating scale (NRS) was lower in the intervention group than in the placebo group at 1, 6, 24 and 72 h after surgery. No statically significant difference was reported at these intervals.

Postoperative use of opioids was lower in the interventional group after 24 h, although there was no statistically significant difference.

Concerning safety, no difference was noticed between interventional and placebo groups.

Breast Reduction

Pain intensity on a numeric rating scale (NRS) was lower in the intervention group than in the placebo group after 24 h. No statically significant difference was reported.

Postoperative use of opioids was lower in the interventional group after 24 h, although there was no statistically significant difference.

No difference was noticed between interventional and placebo groups about AEs incidence.

General anesthesia is the conventional, most frequently used anesthetic technique. Various locoregional anesthetic techniques are also used for breast surgeries. These include local wound infiltration,^[30] tumescent anesthesia,^[31] regional anesthetic techniques, such as pectoral nerve (Pecs) blocks type 1 and 2,^[32,33] serratus plane block (SPB),^[34] and parasternal block (PSB),^[35] pain pump,^[36,37] and intravenous regional block.^[7,38]

We considered continuous IV infusion of lidocaine for our review. Various are the reasons that led us to consider this technique. Local anesthetics exert their pharmacological action through the block of sodium channels in neural tissues, thereby interrupting neuronal transmission. This action is best demonstrated when the drug comes directly in contact of neural tissues. However, the systemic effects of lidocaine are also probably or at least partially, related to this mechanism.^[39] The IV lidocaine shares many of the effects of local anesthetics when used in regional anesthesia techniques. It can lead to better postoperative analgesia, reduced opioid consumption and improved intestinal motility.^[40] In addition to the analgesic action, local anesthetics have anti-inflammatory action, justifying also the use of intravenous lidocaine to modulate the inflammatory response resulting from postoperative pain.^[41]

Locoregional anesthesia provides effective anesthesia and analgesia in the perioperative setting. The beneficial analgesic effect of the regional block is well known, and also confirmed in our analysis. After mastectomy, the use of locoregional anesthesia techniques seems to reduce pain especially in the first hour after the end of the surgery.

Other potentially beneficial effects of locoregional anaesthesia and analgesia on other perioperative outcomes include decreased need for opioids for controlling postoperative pain, decreased postoperative nausea and vomiting, fewer complications and increased patient satisfaction. In our review, there was no statistically significant difference between the analysed anesthesia techniques.

The effective management and relief of postoperative pain plays a vital role in overall surgical outcome. Untreated pain has been linked to prolonged hospital stays, deep venous thrombosis, pulmonary embolism, pneumonia, bowel dysmotility, insomnia, and impaired wound healing.^[42] Reduced occurrence of nausea and vomiting is related to better analgesia and opioids/inhalational anaesthetics sparing effect by regional blocks.^[43,44] All this improves post-operative recovery and shortens hospitalization stay.

Limitations. Our review has several limitations. First, some outcomes were characterized by high levels of heterogeneity. Reasons for this may be attributable to subtle variations in surgical technique and differences in anesthetic and analgesic regimens. Second, for 3 studies included in this review (Campbell et al 2014,^[10]Lanier et al 2018 and Picard et al^[25]), it is not possible to assess whether only regional anesthesia for breast surgery was performed. The impact of locoregional anesthesia on nociception as a "pure" or "adjuvant" technique is different, notably because of the different dosage of local anesthetics. We decided not to exclude these studies and to accept the possible bias during the analysis. Third, many of the included studies had small sample sizes, which decreases their effect and limits external validity. Fourth, another major limitation of this review was the large and unexplained statistical heterogeneity between the studies. Finally, we included two studies (Couceiro et al;^[11] Terkawi et al 2014) analysing the use of i.v. lidocaine. Systemic lidocaine is not "really" a locoregional anesthesia technique, nevertheless we decided to include it in our review accepting the possible bias arising from systemic effects of this local anesthetic.

All these limitations reduced the quality of the evidence for most of the outcomes.

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Next Section

Table 1. PICO criteria for including studies
Population	Patients of at least 18 years undergoing breast surgery.
Intervetion	Postoperative analgesia with locoregional anesthesia techniques.
Comparator	Standard pain treatment.
Outcomes	Pain Intensity, Opioid Consumption, Adverse Events, Patient Satisfaction.
Study TYPE	Randomized Controlled Trial.
Time	From 2010 to present.

Table 2. Studies characteristics
Author, year	Study	Sites	No.	Type of surgery	Anesthesia	Intervention
A. LUMPECTOMY/MASTECTOMY
Campbell et al.,[10] 2014	SB-RCT	New Zeland, 1	79	Lumpectomy/Mastectomy ± ALND	?	Local Infiltration
Couceiro et al.,[11] 2014	DB-RCT	Brazil, 1	44	Mastectomy	GA	IV lidocaine
Cros et al.,[12] 2018	DB-RCT	France, 1Canada, 1	127	Lumpectomy/Mastectomy ± SLNB/ALND	GA	Pecs I
Ferreira Laso et al.,[13] 2014	DB-RCT	Spain, 1	73	Mastectomy	GA	Infusion pump
Gürkan et al.,[14] 2018	SB-RCT	Turkey,?	50	Lumpectomy/Mastectomy ± SLNB/ALND	GA	ESP
Ilfeld et al.,[15] 2014	DB-RCT	US,?	60	Mastectomy ± ALND	Sedation	PVB
Lanier et al .[16] 2018	DB-RCT	US,?	45	Mastectomy + reconstruction ± SLNB/ALND	?	Intercostal + pectoral nerve blocks
Mohamed et al.,[17] 2013	DB-RCT	Egypt,?	140	Mastectomy ± ALND	GA	Local infiltration
Neethu et al.,[18] 2018	RCT	India, 1	60	Mastectomy ± SLNB/ALND	GA	Pecs I - II
Terkawi et al.,[19] 2014	DB-RCT	US,?	71	Mastectomy	GA	IV lidocaine
Versyck et al.,[20] 2017	DB-RCT	Belgium, 1	140	Mastectomy/tumorectomy ±SLNB/ALND	GA	Pecs II
Wang et al.,[21] 2018	SB-RCT	China,?	64	Mastectomy + reconstruction ± ALND	GA	Pecs II
Wang et al.,[22] 2019	RCT	China,?	61	Mastectomy	GA	Pecs I + SPB
Yao et al.,[23] 2019	DB-RCT	China, 1	72	Mastectomy ± ALND	GA	SPB
B. BREAST AUGMENTATION
Gardiner et al.,[24] 2012	SB-RCT	Australia,?	40	BA	Sedation	PVB
Picard et al.,[25] 2017	SB-RCT	France,?	72	BA	?	Local infiltration
Schuitemaker et al.,[26] 2019	DB-RCT	Spain,?	30	BA	GA	Pecs II + SPB
C. BREAST REDUCTION
Christie et al., [27] 2017	DB-RCT	US, 1	40	BR	GA	Tumescent Anaesthesia
Valente et al.,[28] 2014	DB-RCT	Brazil,?	39	BR	GA	Local infiltration

SB-RCT Single-Blind Randomized Controlled Trial, DB-RCT Double-Blind Randomized Controlled Trial, SLNB Sentinel Lymph Node Biopsy, ALND Axillary Lymph Node Dissection, GA General Anesthesia, Pecs Pectoralis nerve block, ESP Erector Spinae Plane block, PVB ParaVertebral Block, SPB Serratus Plane Block, BA Breast Augmentation, BR Breast Reduction;?, not reported

Table 3. Personal and clinical characteristics of patients undergoing lumpectomy/mastectomy
	Patients (n =)		Age (years)		Weight (kg)		Height (cm)		BMI (kg/m²)
	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C
Campbell et al., 2014 [10]	45	34	59.4	61.7	80.7	73.8	163.3	162.3	30.2	28.1
Couceiro et al., 2014 [11]	22	22	47.0	52.4	–	–	–	–	28.1	28.2
Cros et al., 2018 [12]	62	66	60.5	62.0	63.6	65.0	160.0	160.0	24.8	25.6
Ferreira Laso et al., 2014 [13]	34	39	54.8	57.7	67.2	66.7	–	–	–	–
Gürkan et al., 2018 [14]	25	25	49.5	49.8	72.4	73.1	161.0	161.0	27.8	28.2
Ilfeld et al., 2014 [15]	30	30	48.0	49.0	62.0	61.0	165.0	166.0	23.0	24.0
Lanier et al., 2018 [16]	23	22	48.0	50.0	67.0	70.0	160.0	170.0	26.0	26.0
Mohamed et al., 2013 [17]	105	35	39.9	38.9	70.2	69.8	160.6	158.5	27.4	27.9
Neethu et al., 2018 [18]	30	30	50.5	45.6	–	–	–	–	–	–
Terkawi et al., 2014 [19]	34	37	53.0	54.0	–	–	–	–	26.2	28.2
Versyck et al., 2017 [20]	45	40	59.6	58.8	67.3	67.0	165.0	165.0	24.7	24.6
Wang et al., 2018 [21]	30	30	46.8	47.4	–	–	–	–	25.4	24.8
Wang et al., 2019 [22]	32	29	51.3	55.3	58.7	57.6	162.5	161.0	22.3	22.2
Yao et al., 2019 [23]	34	34	46.5	47.7	57.2	56.2	160.9	160.8	22.3	21.9
TOTAL	585	473	51.05 ± 5.6	52.16 ± 6.3	66.65 ± 6.5	66.03 ± 5.8	162.04 ± 1.8	162.74 ± 3.3	25.71 ± 2.3	25.83 ± 2.2

Table 4. NRS at 1, 6, 12, 24 and 48 h after lumpectomy/mastectomy
	Up to 1 h		Up to 6 h		Up to 12 h		Up to 24 h		Up to 48 h
	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C
Campbell et al., 2014 [10]	–	–	1.75	2	–	–	2.3	1.7	1.8	1.25
Couceiro et al., 2014 [11]	–	–	–	–	–	–	–	–	–	–
Cros et al., 2018 [12]	3	3	–	–	–	–	–	–	–	–
Ferreira Laso et al., 2014 [13]	1.6	6.7	–	–	–	–	0.8	4.2	0.4	3.3
Gürkan et al., 2018 [14]	2	2	2	2	0	1	0	1	–	–
Ilfeld et al., 2014 [15]	–	–	–	–	–	–	3.6	3.7	–	–
Lanier et al., 2018 [16]	3	5	4	5	5	4	4	4	–	–
Mohamed et al., 2013 [17]	2.67	3.7	2.43	3.6	2.53	3.8	2.43	3.7	2.43	3.8
Neethu et al., 2018 [18]	1.78	3.08	0.43	0.76	1.20	1.40	0.5	0.53	–	–
Terkawi et al., 2014 [19]	–	–	2.94	3.88	–	–	2.91	2.66	2.72	3.9
Versyck et al., 2017 [20]	0.38	0.20	–	–	–	–	–	–	–	–
Wang et al., 2018 [21]	1.65	4.3	2.45	3.9	1.8	1.9	1	1	–	–
Wang et al., 2019 [22]	1	3	0.8	4.4	1	2	0.5	1.8	0.2	1.6
Yao et al., 2019 [23]	1.3	2.7	1.4	2.4	–	–	1.2	1.8	–	–
TOTAL	1.83 ± 0.81	3.36 ± 1.65	2.02 ± 1.03	3.10 ± 1.29	1.92 ± 1.57	2.35 ± 1.14	1.74 ± 1.29	2.37 ± 1.27	1.51 ± 1.03	2.77 ± 1.12
p	0.02*		0.08		0.63		0.29		0.13

Table 5. Average per patient opioid consumption in PACU and up to 48 h after lumpectomy/mastectomy
	PACU			Up to 48 h
	Group I	Group C	p	Group I	Group C	p
Campbell et al., 2014 [10]	–	–		3.42	7.33^a
Couceiro et al., 2014 [11]	–	–		–	–
Cros et al., 2018 [12]	1.5	3		1.5	3
Ferreira Laso et al., 2014 [13]	0	0.7^a		0	0.7^a
Gürkan et al., 2018 [14]	1	1		5	16^a
Ilfeld et al., 2014 [15]	1	2.4^a		2.5	5.7
Lanier et al., 2018 [16]	8	17		4	5.18
Mohamed et al., 2013 [17]	–	–		0.58	1^a
Neethu et al., 2018 [18]	–	–		1.46	2.03^a
Terkawi et al., 2014 [19]	9.35	9.69		11.02	11.61
Versyck et al., 2017 [20]	0.18	0.33^a		0.20	0.37^a
Wang et al., 2018 [21]	–	–		1.75	5.42^a
Wang et al., 2019 [22]	–	–		–	–
Yao et al., 2019 [23]	–	–		0.73	1.03^a
TOTAL	3.0 ± 3.63	4.87 ± 5.76	0.51	2.68 ± 0.88	4.94 ± 4.61	0.18

^aDifference statistically significant

Table 6. Number of adverse events (AEs) after lumpectomy/mastectomy
AEs	Group I (n =)	Group C (n =)	p
Nausea/Vomiting/PONV	96	139	0.25
Pruritus	7	16	0.47
Hypotension	5	2	0.25
Hypertension	0	1	0.32
Dizzness	2	15	0.06
Bradycardia	2	0	0.32
Hematoma/Bleeding	10	11	0.85
Seroma	10	11	0.91
Alteration of healing	2	3	0.78
Infection	3	2	0.69
DVT	1	1	1.00
PTE	1	1	1.00
Acute respiratory infection	1	1	1.00
Bruising	23	13	0.70
TOTAL	163	216	0.74

Table 7. Patient satisfaction after lumpectomy/mastectomy
	Group I		Group C
	Satisfied	Not satisfied	Satisfied	Not satisfied
Campbell et al., 2014 [10]	–	–	–	–
Couceiro et al., 201 4 [11]	–	–	–	–
Cros et al., 2018 [12]	61	1	64	1
Ferreira Laso et al., 2014 [13]	32	2	37	2
Gürkan et al., 2018 [14]	–	–	–	–
Ilfeld et al., 2014 [15]	–	–	–	–
Lanier et al., 2018 [16]	23	0	23	0
Mohamed et al., 2013 [17]	–	–	–	–
Neethu et al., 2018 [18]	25	5	10	20
Terkawi et al., 2014 [19]	–	–	–	–
Versyck et al., 2017^a [20]	–	–	–	–
Wang et al., 2018 [21]	–	–	–	–
Wang et al., 2019 [22]	23	6	15	17
Yao et al., 2019^b [23]	–	–	–	–
TOTAL	164	14	149	40

^aBoth patient-groups were very satisfied about their management (9.6 ± 0.6 and 9.1 ± 1.8 on a 10-point scale, p = 0.21)
^bPatient satisfaction scores were higher in the SPB group

Table 8. Personal and clinical characteristics of patients undergoing breast augmentation
	Patients (n =)		Age (years)		Weight (kg)		Height (cm)		BMI (kg/m²)
	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C
Gardiner et al., 2012 [24]	20	20	33.4	34.9	–	–	–	–	20.5	20.1
Picard et al., 2017 [25]	29	43	32.4	34.6	–	–	–	–	–	–
Schuitemaker et al., 2019 [26]	15	15	33.0	33.0	52.0	54.0	163.0	163.0	20.0	20.0
TOTAL	64	78	32.93 ± 0.41	34.16 ± 0.83	52.0	54.0	163.0	163.0	20.25 ± 0.25	20.05 ± 20.04

Table 9. NRS at 1, 6, 24 and 72 h after breast augmentation
	Up to 1 h		Up to 6 h		Up to 24 h		Up to 72 h
	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C
Gardiner et al., 2012 [24]	3.9	5.2	–	–	–	–	3.3	4.7
Picard et al., 2017 [25]	–	–	–	–	4.8	5.1	2.8	3.7
Schuitemaker et al., 2019 [26]	2.9	5.3	3.0	3.0	2.5	3.0	–	–
TOTAL	3.4 ± 0.5	5.25 ± 0.05	3.0	3.0	3.65 ± 1.15	4.05 ± 1.05	3.05 ± 0.25	4.2 ± 0.5
p	0.06		–		0.82		0.17

Table 10. Personal and clinical characteristics of patients undergoing breast reduction
	Patients, n		Age, years		Weight, kg		Height, cm		BMI, kg/m²
	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C	Group I	Group C
Christie et al., 2017 [27]	20	20	41.0	42.0	–	–	–	–	33.0	31.0
Valente et al., 2014 [28]	18	20	35.57	35.57	–	–	–	–	–	–
TOTAL	38	40	38.28 ± 2.71	38.78 ± 3.21	–	–	–	–	33.0	31.0