Oncological Breast Surgery 2019

Breast surgery-Specific Evidence

Data table: Paracetamol and NSAIDs/COX-2-selective inhibitors for pain management after breast surgery

Arguments for…

• One study compared paracetamol, metamizole and placebo. 42% of patients receiving paracetamol did not require rescue analgesia compared with 4% in the placebo group and 4% in the metamizole group (n=79) (Ohnesorge 2009; LoE 1)
• Another study documented that paracetamol 1g administered at the end of surgery improved pain control during recovery compared with placebo (n=65) (De Oliveira 2018; LoE 1)
• Pain control with paracetamol was documented to be equivalent to metamizole in another study (n=40) (Kampe 2006; LoE 1). However, there were insufficient numbers in this study to draw conclusions.
• Incidence of nausea and constipation was reduced in ambulatory patients receiving paracetamol and ibruprofen vs a combination of paracetamol, codeine and caffeine whilst the pain reduction was comparable (n=141) (Mitchell 2012; LoE 1)

Arguments against…

• Only one study in the search period specifically examined postoperative pain control with NSAIDs. The addition of systemic COX-2 inhibitors (parecoxib and celecoxib) to PVB decreased the intensity of pain on movement at day five but had no effect on the incidence of postoperative hyperalgesia (n=94) (Van Helmond 2016; LoE 1)

PROSPECT Recommendations

• Paracetamol (Grade B) and NSAID (Grade A) or COX-2-specific inhibitor (Grade B) are recommended for minor and major breast surgery, administered pre-operatively or intra-operatively and continued postoperatively, unless there are contra-indications.
• The use of NSAIDs (Grade A) is supported by studies performed before 2006 in breast surgery (Chan 1996, Priya 2002), although there are no recent data.
• The analgesic benefits and opioid-sparing effects of these simple analgesics are well described (Martinez 2017, Ong 2010).

Breast surgery-Specific Evidence

Data table: Gabapentinoids for pain management after breast surgery

Arguments for…

• Two meta-analyses found that gabapentin reduced pain scores vs placebo in the PACU and 24 h postoperatively (Rai 2017 and Jiang 2018).
  • The two meta-analyses of parallel group, placebo-controlled RCTs evaluated the efficacy of the pre-operative use of gabapentin or pregabalin for the treatment of acute and chronic postoperative pain following breast cancer surgery (Rai 2017 and Jiang 2018).
  • Doses of gabapentin ranged between 300 mg and 1200 mg.
  • A sub-group analysis was conducted according to the dose of gabapentin (< 900 mg or ≥ 900 mg daily) and documented that a high dose of gabapentin (> 900 mg daily) was superior in terms of pain scores (Jiang 2018).
• In six studies, gabapentin significantly reduced 24-h morphine consumption vs placebo (Rai 2017).
• In one meta-analysis, pre-operative pregabalin reduced pain scores and morphine consumption in the PACU but there was no significant difference in pain scores at 24 h (Rai 2017).
  • Doses of pregabalin ranged between 150 mg and 900 mg (Rai 2017).
• No significant differences in gabapentin-related side effects were reported (Rai 2017 and Jiang 2018).

Arguments against…

• Meta-analyses recorded a large dose range for gabapentinoids, with no documented dose-response effect (Rai 2017 and Jiang 2018).
• Pregabalin increased the incidence of sedation (Rai 2017 and Jiang 2018).

PROSPECT Recommendations

• Pre-operative gabapentin is recommended (Grade A) for minor and major breast surgery as it has been shown to reduce postoperative pain scores and opioid consumption. However, it is recommended with caution as high doses could induce side-effects that are particularly concerning in ambulatory patients.
• Pre-operative pregabalin is not recommended as the observed pain relief did not last up to 24 h.

Breast surgery-Specific Evidence

Data table: IV dexamethasone for pain management after breast surgery

Arguments for…

• Two studies reported patients receiving IV dexamethasone had significantly less pain up to 24 h after surgery compared with placebo (Cortés-Flores 2018; LoE 2; n=80; Gómez-Hernández 2010;  LoE 1; n=70). More patients required rescue analgesics in the control groups than in the dexamethasone groups
• Dexamethasone 8 mg administered IV 1 h before surgery reduced PONV at 6 h postoperatively vs placebo (Cortés-Flores 2018; LoE 2; n=80; Gómez-Hernández 2010;  LoE 1; n=70). Consequently, the frequency of use of anti-emetic medications was higher in the control groups

PROSPECT Recommendations

• Single-dose IV dexamethasone is recommended (Grade B) for minor and major breast surgery as it provides additional pain relief as well as reducing analgesia use and the incidence of PONV.

Breast Surgery-Specific Evidence

Data table: Thoracic PVB for pain management after breast surgery

Arguments for…

• Three meta-analyses investigated the postoperative effects of thoracic PVB, finding a reduction in pain scores and opioid consumption compared with controls:
  • Thoracic PVB (±GA) resulted in lower postoperative pain scores compared with GA, up to 48 h (Schnabel 2010)
  • Thoracic PVB reduced pain scores at 1 and 6 h postoperatively, opioid consumption and the incidence of postoperative nausea and vomiting compared with GA (Tahiri 2011)
  • Thoracic PVB decreased postoperative pain scores at rest and movement at the first 2, 24, 48, and 72 hours, and modestly decreased opioid consumption compared with no PVB (Terkawi 2015). The average length of hospital stay was shorter in patients who received PVB, but the difference was small and probably not clinically relevant (Terkawi 2015).
• Two studies using ultrasound guidance for thoracic PVB found analgesic benefits compared with controls: reduced pain scores and opioid consumption vs sham-block (Abdallah 2014; LoE 1; n=66); reduced opioid consumption vs GA in PACU (Sundarathiti 2015; LoE 1; n=70).
• Three studies using no ultrasound guidance reported reduced pain scores and opioid consumption with PVB vs GA (Das 2012; LoE 1; n=59), vs PCA morphine (Fallatah 2016; LoE 1; n=40) and vs placebo (in PACU) (Moller 2007; LoE 1; n=79).
  • However, in one study, pain scores at 24 hours after surgery were significantly lower with GA alone than with PVB (no ultrasound guidance) + GA, and there was no significant difference at 0 and 6 h (Boughey 2009; LoE 1; n=80).
• One of two studies comparing single-level and multiple-level PVB found reduced postoperative analgesic consumption with multiple injections but no significant difference in the incidence of PONV (Kasimahanti 2016; LoE 2; n=60). The other study reported no significant difference in pain scores or analgesic consumption but the time required to perform a single-injection PVB was shorter than for multiple-injection PVB (5 min vs 10 min; median difference 4 min; 95%CI -6 to -3 min; p<0.001) (Uppal 2017; LoE 1; n=70).
• Four of six studies reported that continuous PVB was associated with postoperative analgesic benefits: reduced pain scores and opioid consumption vs GA (Wu 2015; LoE 1; n=386); reduced pain scores up to postoperative day 5 vs GA + systemic analgesia (Iohom 2006; LoE 1; n=29); reduced pain scores at 4 h postoperatively vs GA (Burlacu 2006; LoE 1; n=52); continuous paravertebral infusion administered on an ambulatory basis was associated with lower pain scores and improved functional outcomes over three postoperative days (n=60) (Ilfeld 2014; LoE 1; n=60).
  • One study reported that the use of continuous PVB provided no advantage to single injection PVB in terms of postoperative pain, nausea, mood state, level of symptom distress and recovery time (Buckenmaier 2010; LoE 2; n=73)
  • One study found a similar incidence of chronic pain in patients who recived continuous PVB and those who did not, although continuous PVB was associated with a reduced severity of chronic pain symptoms (Karmakar 2014; LoE 1; n=180).
• A study comparing PVB (no ultrasound guidance) with interpleural injection found no significant difference in pain scores or analgesic consumption (Kundra 2013; LoE 1; n=120).
• A number of studies investigated the analgesic effects of alternative components of PVB:
  • One study found that PVB (using ultrasound guidance) with 0.5% levobupicaine alone was associated with lower pain scores and analgesic consumption than PVB with 2% lidocaine + 0.5% levobupivacaine (Zupcic 2017; LoE 1; n=80).
  • One study reported that pain scores were significantly lower at rest and movement for 24 h postoperatively for patients who received PVB with 0.25% bupivacaine + epinephrine 5 µg/ml + fentanyl 2 µg/ml or 0.5% bupivacaine + epinephrine 5 µg/ml compared with those who received 0.25% bupivacaine + epinephrine 5 µg/ml or normal saline placebo (no ultrasound guidance) (Bhuvaneswari 2012; LoE 2; n=48).
  • Two studies found that addition of dexmedetomidine to PVB (no ultrasound guidance) provided longer analgesia and reduced opioid consumption (Mohta 2016; LoE 2; n=45; Mohamed 2014; n=60).
  • One study reported the addition of clonidine enhanced the analgesic efficacy of guided PVB up to 3 days postoperatively (Naja 2013; n=60).
  • One study found no significant difference in pain scores or analgesic consumption when ketamine or tramadol were added to bupivacaine for PVB (no ultrasound guidance) (Omar 2011; LoE 1; n=62).
  • In one study, bupivacaine was associated with lower pain scores than ropivacaine for PVB (no ultrasound guidance), but there was no significant difference in analgesic consumption (Sahu 2016; LoE 1; n=70).
  • One study of continuous PVB (no ultrasound guidance) reported no significant difference in pain scores but postoperative PCA morphine consumption was decreased when fentanyl or clonidine were added to levobupivacaine in the PVB. However, there was an increase in vomiting and hypotension with fentanyl and clonidine, respectively (Burlacu 2006; LoE 1; n=52).

PROSPECT Recommendations

• PVB is recommended (Grade A) as the first-choice regional analgesic technique for major breast surgery (e.g. mastectomy with or without axillary node dissection)
  • Studies demonstrated that this intervention was associated with: lower postoperative pain scores; lower systemic analgesia consumption; reduced PONV; and a shorter length of hospital stay than GA alone, although the studies did not follow an enhanced recovery programme
• Continuous PVB should be considered for major breast surgery if a catheter is in place (Grade B)
  • A single-injection PVB requires a shorter time to perform and is less labour intensive as compared with the multiple-injection technique or placement of a paravertebral catheter
  • Some studies report an improvement in functional outcomes and less severe chronic pain after the use of continuous PVB
  • These findings should be interpreted with caution as these studies did not use ‘basic’ non-opioid analgesics (i.e. paracetamol, NSAIDs or COX-2 selective inhibitors) in a fully implemented multimodal analgesia programme
  • A cost effectiveness study reported higher costs of continuous PVB (Offodile, 2017); however, these costs would be offset by the reduced duration of hospital stay (Terkawi 2015, Abdallah 2014, Fallatah 2016, Mohta 2016)
• PVB cannot reliably provide sufficient analgesia to the axilla (i.e. T1 nerve distribution) (Pawa 2018) and supplemental local anaesthetic wound infiltration may be beneficial for these cases

Breast Surgery-Specific Evidence

Data table: PECS block for pain management after breast surgery

Arguments for…

• Three meta-analyses reported reduced pain scores and lower morphine consumption with PECS blocks vs no block or placebo (Versyck 2019, n=815; Hussain 2019, n=887; Zhao, 2019, n=993).
• PECS-2 blocks were associated a reduction in pain scores in four studies (Bashandy 2015; LoE 1; n=120; Versyck 2017; LoE 1; n=140; Kamiya 2018; LoE 1; n=60; Senapathi 2019; LoE 1; n=50) but no significant difference in pain scores in one study (Al Ja’bari 2019; LoE 1; n=50).
• PECS-2 blocks were associated with a reduction in postoperative opioid consumption compared with no block or placebo in four studies (Bashandy 2015; LoE 1; n=120; Versyck 2017; LoE 1; n=140; Al Ja’bari 2019; LoE 1; n=50; Senapathi 2019; LoE 1; n=50)
• One study evaluated the effect of adding a PECS-1 block to multimodal analgesia, including local anaesthetic infiltration (Cros 2018; LoE 1; n=128). No reduction in pain scores was documented postoperatively in patients having a PECS-1 block but the sub-group of patients scheduled for major breast surgery (n=29) had lower pain scores after a PECS block.
• Two meta-analyses comparing PECS block with PVB reported similar results for pain reIief and analgesic consumption (Versyck 2019 and Hussain 2019).
• Three studies comparing PECS-2 block with PVB documented lower pain scores in patients having a PECS-2 block: during the first 2 hours postoperatively (Kulhari 2016; LoE 1; n=40); up to 12 hours postoperatively (Wahba 2014; LoE 1; n=60); and during 24 hours postoperatively (Syal 2017; LoE 2; n=65).
  • However, one of the studies reported that after 18 hours, patients in the PVB group had lower pain scores than patients in the PECs group (Wahba 2014; LoE 1).
  • Two of the three studies reported reduced morphine consumption in the PECS-2 block groups (Wahba 2014; LoE 1; n=60; Kulhari 2016; LoE 1; n=40); the other found no significant difference (Syal 2017; LoE 2; n=65).
• One study found a reduction in pain scores and analgesic consumption with PECS blocks compared with spinal anaesthesia (Eldeen 2016; LoE1; n=40).
• One study compared PECS block with erector spinae plane (ESP) block (Altiparmak 2019; LoE1; n=38). Initial pain scores were similar with both blocks, however became quickly inferior in the ESP block group and postoperative opioid consumption was also inferior in the ESP block group.
• One study reported a reduction in postoperative opioid consumption with addition of ketamine to bupivacaine for PECS block (Othman 2016; LoE 2; n=60).

Arguments against…

• In one study, the combination of a transversus thoracic muscle plane block with PECS-2 blocks provided lower pain scores and less rescue analgesia consumption than PECS block alone (Ueshima 2017; LoE 1; n=70).

PROSPECT Recommendations

• PECS block is recommended for major breast surgery if no axillary node dissection is performed or if PVB is contraindicated (Grade A), but data are limited and the procedure can not anatomically provide adequate analgesia to the axilla.
• Evidence to guide the choice between PECS-1, PECS-2 and serratus plane blocks is limited.

Breast Surgery-Specific Evidence

Data table: Serratus plane block for pain management after breast surgery

Arguments for…

• Compared with placebo, serratus plane block provided lower pain scores at rest but no significant difference in postoperative opioid consumption (Yao 2019; LoE 1; n=72).

Arguments against…

• In two studies, serratus plane block was compared with PVB and was less effective: total rescue morphine consumption was significantly higher in the serratus plane block group in both studies (Gupta 2017; LoE 1; n=50; Hetta 2016; LoE 1; n=64) and pain scores were higher at 8h, 16h and 24h in one study (Hetta 2016; LoE 1; n=64).
• In one study, different volumes of the same local anaesthetic solution (40 ml vs 20 ml ropivacaine 0.375%) used for serratus plane block provided no difference in pain relief (Kunigo 2017; LoE 1).

PROSPECT Recommendations

• Serratus plane block is not recommended as data are limited and inconsistent.

Breast Surgery-Specific Evidence

Data table: Interfascial plane block for pain management after breast surgery

Arguments for…

• Patients receiving erector spinae plane block reported no difference in pain scores but had decreased morphine consumption compared with GA alone (Gurkan 2018; LoE 1; n=50; Singh 2019; LoE 1; n=40).

Arguments against…

• Compared with PECS block, erector spinae plane block initially provided no difference in pain scores, but after the first postoperative hour, pain scores and opioid consumption were both lower in the PECS block group (Altiparmak 2019; LoE1; n=38).
• Retrolaminar plane block was inferior to PVB in the first 24 h in one RCT (Murouchi 2016; LoE 2; n=30). This is the only breast cancer study investigating retrolaminar block.

PROSPECT Recommendations

• Interfascial plane blocks such as erector spinae plane block and retrolaminar plane block are not recommended due to limited procedure-specific evidence.
• Conflicting results suggest that further studies are needed to assess their use compared with PVB and PECS blocks in breast surgery.

Breast Surgery-Specific Evidence

Data Table: Local Anaesthetic Wound Infiltration for pain relief after breast surgery

Arguments for…

• A meta-analysis including 8 RCTs related to oncological breast surgery that used ropivacaine, bupivacaine or lidocaine for LA wound infiltration, found there was a reduction in pain scores observed in four trials and a reduction in rescue opioid consumption in two trials. However, the effect never lasted more than 24 h and was most commonly limited to the sixth hour (Byager 2014).

Arguments against…

• In three of four studies comparing LA wound infiltration with PVB, analgesia was improved in the group who had PVB, with lower pain scores, and in one study, a reduction in rescue analgesic requirement (Syal 2017; LoE 2; n=65), Bansal 2012; LoE 1; n=40; Sidiropoulou 2008; LoE 1; n=48).
  • In one of those studies, pain scores were lower with single-injection PVB than with continuous LA wound infiltration up to 4 h postoperatively, but continuous LA wound infiltration was associated with lower pain scores at 16 h and 24 h (Sidiropoulou 2008;  LoE 1; n=48).
  • Compared with continuous PVB, one study reported that LA wound infiltration was equally effective in terms of pain control (Bouman 2014; LoE 1; n=36).

PROSPECT Recommendations

• LA wound infiltration should be considered in patients scheduled for minor-to-moderately invasive surgical procedures (e.g. lumpectomy and partial mastectomy) (Grade A), although it provides postoperative analgesia of a limited duration.
  • Postoperative pain after these procedures is typically mild-to-moderate and the intensity decreases over the first couple of postoperative days.
• LA wound infiltration may be added to regional analgesia techniques in major breast surgery (Grade A).
  • LA wound infiltration may be considered in cases where PECS block and PVB do not provide appropriate analgesia to the axilla (i.e. T1 nerve distribution).