Skip to main content

Advertisement

SpringerLink
Log in

Perioperative Breast Analgesia: a Systematic Review of the Evidence for Perioperative Analgesic Medications

  • Acute Pain Medicine (R Urman, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Breast surgery is common and may result in significant acute as well as chronic pain. A wide range of pharmacologic interventions is available including opioids, non-steroidal anti-inflammatory drugs (NSAIDs), N-methyl-d-aspartate (NMDA) receptor antagonists, anticonvulsants, and other non-opioids with analgesic properties. We present a review of the evidence for these pharmacologic interventions. A literature search of the MEDLINE database was performed via PubMed with combined terms related to breast surgery, anesthesia, and analgesia. Articles were limited to randomized controlled trial (RCT) design, adult patients undergoing elective surgery on the breast (not including biopsy), and pharmacologic interventions only. Article titles and abstracts were screened, and risk of bias assessments were performed.

Recent Findings

The search strategy initially captured 7254 articles of which 60 articles met the full inclusion criteria. Articles were organized according to intervention: 6 opioid agonists, 14 NSAIDs and acetaminophen, 4 alpha-2 agonists, 7 NMDA receptor antagonists, 6 local anesthetics, 7 steroids, 15 anticonvulsants (one of which also discussed an NMDA antagonist), 1 antiarrhythmic, and 2 serotonin reuptake inhibitors (one of which also studied an anticonvulsant).

Summary

A wide variety of medications is effective for perioperative breast analgesia, but results vary by agent and dose. The most efficacious are likely NSAIDs and anticonvulsants. Some agents may also decrease the incidence of chronic postoperative pain, including flurbiprofen, gabapentin, venlafaxine, and memantine. While many individual agents are well studied, optimal combinations of analgesic medications remain unclear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AV:

Atrioventricular node

CNS:

Central nervous system

COX:

Cyclooxygenase

EMLA:

Eutectic mixture of local anesthetics

GABA:

Gamma-aminobutyric acid

IM:

Intramuscular

IV:

Intravenous

LAST:

Local anesthetic systemic toxicity

MAOIs:

Monoamine oxidase inhibitors

NMDA:

N-Methyl-d-aspartate

NSAIDs:

Non-steroidal anti-inflammatory drugs

PACU:

Postanesthesia care unit

PMPS:

Postmastectomy pain syndrome

PONV:

Postoperative nausea and vomiting

RCT:

Randomized controlled trial

SNRIs:

Serotonin and norepinephrine reuptake inhibitors

SSRIs:

Selective serotonin reuptake inhibitors

TCAs:

Tricyclic antidepressants

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. American Cancer Society. Breast cancer facts and figures. 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics

  2. American Society of Plastic Surgeons. Plastic surgery statistics report. 2018. https://www.plasticsurgery.org/news/plastic-surgery-statistics

  3. Vilholm OJ, Cold S, Rasmussen L, Sindrup SH. The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer. Br J Cancer. 2008;99(4):604–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cheville AL, Tchou J. Barriers to rehabilitation following surgery for primary breast cancer. J Surg Oncol. 2007;95(5):409–18.

    Article  PubMed  Google Scholar 

  5. Roth RS, Lowery JC, Davis J, Wilkins EG. Persistent pain following postmastectomy breast reconstruction: long-term effects of type and timing of surgery. Ann Plast Surg. 2007;58(4):371–6.

    Article  CAS  PubMed  Google Scholar 

  6. Belfer I, Schreiber KL, Shaffer JR, Shnol H, Blaney K, Morando A, et al. Persistent postmastectomy pain in breast cancer survivors: analysis of clinical, demographic, and psychosocial factors. J Pain. 2013;14(10):1185–95.

    Article  PubMed  Google Scholar 

  7. Gartner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H. Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA. 2009;302(18):1985–92.

    Article  PubMed  Google Scholar 

  8. Rothemund Y, Grusser SM, Liebeskind U, Schlag PM, Flor H. Phantom phenomena in mastectomized patients and their relation to chronic and acute pre-mastectomy pain. Pain. 2004;107(1–2):140–6.

    Article  PubMed  Google Scholar 

  9. Ahmed A, Bhatnagar S, Rana SP, Ahmad SM, Joshi S, Mishra S. Prevalence of phantom breast pain and sensation among postmastectomy patients suffering from breast cancer: a prospective study. Pain Pract. 2014;14(2):E17-28.

    Article  PubMed  Google Scholar 

  10. van Elk N, Steegers MA, van der Weij LP, Evers AW, Hartman EH, Wilder-Smith OH. Chronic pain in women after breast augmentation: prevalence, predictive factors and quality of life. Eur J Pain. 2009;13(6):660–1.

    Article  PubMed  Google Scholar 

  11. Cho AR, Kwon JY, Kim KH, Lee HJ, Kim HK, Kim ES, et al. The effects of anesthetics on chronic pain after breast cancer surgery. Anesth Analg. 2013;116(3):685–93.

    Article  CAS  PubMed  Google Scholar 

  12. Bokhari FN, McMillan DE, McClement S, Daeninck PJ. Pilot study of a survey to identify the prevalence of and risk factors for chronic neuropathic pain following breast cancer surgery. Oncol Nurs Forum. 2012;39(2):E141–9.

    Article  PubMed  Google Scholar 

  13. Fassoulaki A, Melemeni A, Staikou C, Triga A, Sarantopoulos C. Acute postoperative pain predicts chronic pain and long-term analgesic requirements after breast surgery for cancer. Acta Anaesthesiol Belg. 2008;59(4):241–8.

    CAS  PubMed  Google Scholar 

  14. Iohom G, Abdalla H, O’Brien J, Szarvas S, Larney V, Buckley E, et al. The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery. Anesth Analg. 2006;103(4):995–1000.

    Article  CAS  PubMed  Google Scholar 

  15. Poleshuck EL, Katz J, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al. Risk factors for chronic pain following breast cancer surgery: a prospective study. J Pain. 2006;7(9):626–34.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Andersen KG, Duriaud HM, Jensen HE, Kroman N, Kehlet H. Predictive factors for the development of persistent pain after breast cancer surgery. Pain. 2015.

  17. Wallace MS, Wallace AM, Lee J, Dobke MK. Pain after breast surgery: a survey of 282 women. Pain. 1996;66(2–3):195–205.

    Article  CAS  PubMed  Google Scholar 

  18. •• Woodworth GE, Ivie R, Nelson S, Walker C and Maniker RB. Perioperative breast analgesia: a review of anatomy and regional techniques. Reg Anes Pain Med. 2017;42(5):609-631. This systematic review summarized the evidence for procedural interventions such as epidural, paravertebral, and peripheral nerve blocks to treat perioperative pain after breast surgery. Epidural and paravertebral blocks were noted to be effective. These procedures ideally complement a multimodal analgesic medication regimen.

  19. Pasternak GW. Mu opioid pharmacology: 40 years to the promised land. Adv Pharmacol. 2017;82:261–91.

    Article  CAS  PubMed  Google Scholar 

  20. Kim R. Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence. J Transl Med. 2018;16(1):8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sun T, Sacan O, White PF, Coleman J, Rohrich RJ, Kenkel JM. Perioperative versus postoperative celecoxib on patient outcomes after major plastic surgery procedures. Anesth Analg. 2008;106(3):950–8.

    Article  CAS  PubMed  Google Scholar 

  22. Murata-Ooiwa M, Tsukada S, Wakui M. Intravenous acetaminophen in multimodal pain management for patients undergoing total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. J Arthroplasty. 2017;32(10):3024–8.

    Article  PubMed  Google Scholar 

  23. Bonde C, Khorasani H, Hoejvig J, Kehlet H. Cyclooxygenase-2 inhibitors and free flap complications after autologous breast reconstruction: a retrospective cohort study. J Plast Reconstr Aesthet Surg. 2017;70(11):1543–6.

    Article  PubMed  Google Scholar 

  24. Richards C. The effect of opioids, alcohol, and nonsteroidal anti-inflammatory drugs on fracture union. Orthop Clin North Am. 2017;48:433–43.

    Article  PubMed  Google Scholar 

  25. Bosek V, Cox CE. Comparison of analgesic effect of locally and systemically administered ketorolac in mastectomy patients. Ann Surg Oncol. 1996;3(1):62–6.

    Article  CAS  PubMed  Google Scholar 

  26. Brubaker L, Kendall L, Reina E. Multimodal analgesia: a systematic review of local NSAIDs for non-ophthalmologic postoperative pain management. Int J Surg. 2016;32:158–66.

    Article  PubMed  Google Scholar 

  27. Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M. The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. J Neurosurg Anesthesiol. 2013;25(1):16–24.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, Skrivanek G, Macaluso A, Shah M, Provost DA. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg. 2008;106(6):1741–8.

    Article  CAS  PubMed  Google Scholar 

  29. Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012;116(6):1312–22.

    Article  CAS  PubMed  Google Scholar 

  30. Nguyen V, Tiemann D, Park E, Salehi A. Alpha-2 agonists. Anesthesiol Clin. 2017;35(2):233–45.

    Article  PubMed  Google Scholar 

  31. Davies SN, Lodge D. Evidence for involvement of N-methylaspartate receptors in ‘wind-up’ of class 2 neurones in the dorsal horn of the rat. Brain Res. 1987;424(2):402–6.

    Article  CAS  PubMed  Google Scholar 

  32. Davar G, Hama A, Deykin A, Vos B, Maciewicz R. MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy. Brain Res. 1991;553(2):327–30.

    Article  CAS  PubMed  Google Scholar 

  33. Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013;19(6):370–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Romanelli F, Smith KM. Dextromethorphan abuse: clinical effects and management. J Am Pharm Assoc. 2009;49(2):e20–5.

    Article  Google Scholar 

  35. Kornhuber J, Weller M, Schoppmeyer K, Riederer P. Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl. 1994;43:91–104.

    CAS  PubMed  Google Scholar 

  36. Fozzard HA, Lee PJ, Lipkind GM. Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des. 2005;11(21):2671–86.

    Article  CAS  PubMed  Google Scholar 

  37. Pere P, Lindgren L, Vaara M. Poor antibacterial effect of ropivacaine: comparison with bupivacaine. Anesthesiology. 1999;91(3):884–6.

    Article  CAS  PubMed  Google Scholar 

  38. De Oliveira GS Jr, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012;115(2):262-7.

  39. Vigneault L, Turgeon AF, Côté D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011;58(1):22–37.

    Article  PubMed  Google Scholar 

  40. Xu J, Yang J, Lin P, Rosenquist E, Cheng J. Intravenous therapies for complex regional pain syndrome: a systematic review. Anesth Analg. 2016;122(3):843–56.

    Article  CAS  PubMed  Google Scholar 

  41. Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2019;2019(10).

  42. De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2011;115(3):575-88.

  43. Aasboe V, Raeder JC, Groegaard B. Betamethasone reduces postoperative pain and nausea after ambulatory surgery. Anesth Analg. 1998;87(2):319–23.

    Article  CAS  PubMed  Google Scholar 

  44. Goppelt-Struebe M, Wolter D, Resch K. Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase. Br J Pharmacol. 1989;98(4):1287–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Moghadam-Kia S, Werth VP. Prevention and treatment of systemic glucocorticoid side effects. Int J Dermatol. 2010;49(3):239–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mahran E, Hassan ME. Comparison of pregabalin versus ketamine in postoperative pain management in breast cancer surgery. Saudi J Anaesth. 2015;9(3):253–7.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Calandre EP, Rico-Villademoros F, Slim M. Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Rev Neurother. 2016;16(11):1263–77.

    Article  CAS  PubMed  Google Scholar 

  48. Taylor CP. Mechanisms of action of gabapentin. Rev Neurol (Paris). 1997;153(Suppl 1):S39-45.

    Google Scholar 

  49. Fuzier R, Serres I, Guitton E, Lapeyre-Mestre M, Montastruc JL. French Network of Pharmacovigilance Centres. Adverse drug reactions to gabapentin and pregabalin: a review of the French pharmacovigilance database. Drug Saf. 2013;36(1):55–62.

  50. •• Verret M, Lauzier F, Zarychanski R, Perron C, Savard X, Pinard AM, Leblanc G, Cossi MJ, Neveu X, Turgeon AF. Canadian Perioperative Anesthesia Clinical Trials (PACT) Group. Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis. Anesthesiology. 2020;133(2):265–279. This meta-analysis pooled 281 studies of perioperative gabapentinoid use and showed minimal benefit across all surgical types, but other reviews on specific surgical interventions like breast surgery have shown larger effects of gabapentinoids on perioperative pain.

  51. Parker RB, McCollam PL. Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia. Clin Pharm. 1990;9(4):261–71.

    CAS  PubMed  Google Scholar 

  52. Vincenzi F, Pasquini S, Borea PA, Varani K. Targeting adenosine receptors: a potential pharmacological avenue for acute and chronic pain. Int J Mol Sci. 2020;21(22):8710.

    Article  CAS  PubMed Central  Google Scholar 

  53. Segerdahl M, Ekblom A, Sandelin K, Wickman M, Sollevi A. Peroperative adenosine infusion reduces the requirements for isoflurane and postoperative analgesics. Anesth Analg. 1995;80(6):1145–9.

    CAS  PubMed  Google Scholar 

  54. Doi T, Kuzuna S, Maki Y. Spinal antinociceptive effects of adenosine compounds in mice. Eur J Pharmacol. 1987;137(2–3):227–31.

  55. Vapaatalo H, Onken D, Neuvonen PJ, Westermann E. Stereospecificity in some central and circulatory effects of phenylisopropyl-adenosine (PIA). Arzneimittelforschung. 1975;25(3):407–10.

    CAS  PubMed  Google Scholar 

  56. Jin X, Mi W. Adenosine for postoperative analgesia: a systematic review and meta-analysis. PLoS One. 2017;12(3):e0173518.

  57. Taylor C, Fricker AD, Devi LA, Gomes I. Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cell Signal. 2005;17(5):549–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Miller, Ronald D. Miller’s anesthesia. 7th ed. Philadelphia, PA: Churchill Livingstone/Elsevier, 2010.

  59. Humble SR, Dalton AJ, Li L. A systematic review of therapeutic interventions to reduce acute and chronic post-surgical pain after amputation, thoracotomy or mastectomy. Eur J Pain. 2015;19(4):451–65.

    Article  CAS  PubMed  Google Scholar 

  60. Castro-Alves LJ, Oliveira de Medeiros AC, Neves SP, Carneiro de Albuquerque CL, Modolo NS, De Azevedo VL, De Oliveira GS Jr. Perioperative duloxetine to improve postoperative recovery after abdominal hysterectomy: a prospective, randomized, double-blinded, placebo-controlled study. Anesth Analg. 2016;122(1):98–104.

  61. Riediger C, Schuster T, Barlinn K, Maier S, Weitz J, Siepmann T. Adverse effects of antidepressants for chronic pain: a systematic review and meta-analysis. Front Neurol. 2017;8:307.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Amr YM, Yousef AA. Evaluation of efficacy of the perioperative administration of venlafaxine or gabapentin on acute and chronic postmastectomy pain. Clin J Pain. 2010;26(5):381–5.

    Article  PubMed  Google Scholar 

  63. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.

    Article  CAS  PubMed  Google Scholar 

  64. Kampe S, Warm M, Kaufmann J, Hundegger S, Mellinghoff H, Kiencke P. Clinical efficacy of controlled-release oxycodone 20 mg administered on a 12-h dosing schedule on the management of postoperative pain after breast surgery for cancer. Curr Med Res Op. 2004;20(2):199–202.

    Article  CAS  Google Scholar 

  65. Silvasti M, Svartling N, Pitkänen M, Rosenberg PH. Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction. Eur J Anaesth. 2000;17(7):448–55.

    Article  CAS  Google Scholar 

  66. Besic N, Smrekar J, Strazisar B. Acute pain and side effects after tramadol in breast cancer patients: results of a prospective double-blind randomized study. Sci Rep. 2020;10(1):18766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yarussi A, Sands R, Edge S, Lema MJ, de Leon-Casasola OA. Evaluation of peripheral morphine analgesia for lumpectomy and axillary node dissection: a randomized, double-blind, placebo-controlled study. Regional Anesth Pain Med. 1999;24(2):142–5.

    CAS  Google Scholar 

  68. Shen X, Wang F, Xu S, Ma L, Liu Y, Feng S, et al. Comparison of the analgesic efficacy of preemptive and preventive tramadol after lumpectomy. Pharmacological reports: PR. 2008;60(3):415–21.

    CAS  PubMed  Google Scholar 

  69. Kampe S, Wolter K, Warm M, Dagtekin O, Shaheen S, Landwehr S. Clinical equivalence of controlled-release oxycodone 20 mg and controlled-release tramadol 200 mg after surgery for breast cancer. Pharmacology. 2009;84(5):276–81.

    Article  CAS  PubMed  Google Scholar 

  70. Parsa AA, Soon CWM, Parsa FD. The use of celecoxib for reduction of pain after subpectoral breast augmentation. Aesthetic Plast Surg. 2005;29(6):441–5.

    Article  PubMed  Google Scholar 

  71. •• van Helmond N, Steegers MA, Filippini-de Moor GP, Vissers KC, Wilder-Smith OH. Hyperalgesia and persistent pain after breast cancer surgery: a prospective randomized controlled trial with perioperative COX-2 inhibition. PLOS One. 2016;11(12):e0166601. An RCT finding that COX-2 inhibitors can be valuable in preventing acute postoperative pain on movement, but their role in preventing pain sensitization and persistent pain is limited.

  72. Gehling M, Arndt C, Behrendt IC, Wulf H, Eberhart LHJ. Is the prophylactic use of non-opioids for post-operative analgesia always indicated? A randomized controlled trial in breast surgery. Ambul Surg. 2011;16(4):93–8.

    Google Scholar 

  73. Legeby M, Sandelin K, Wickman M, Olofsson C. Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction. Acta Anaesthesiol Scand. 2005;49(9):1360–6.

    Article  CAS  PubMed  Google Scholar 

  74. Sun M, Liao Q, Wen L, Yan X, Zhang F, Ouyang W. Effect of perioperative intravenous flurbiprofen axetil on chronic postmastectomy pain. Journal of Central South University Medical sciences. 2013;38(7):653–60.

    CAS  PubMed  Google Scholar 

  75. Ohnesorge H, Bein B, Hanss R, Francksen H, Mayer L, Scholz J, et al. Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial. Eur J Anaesth. 2009;26(8):648–53.

    Article  CAS  Google Scholar 

  76. Nonaka T, Hara M, Miyamoto C, Sugita M, Yamamoto T. Comparison of the analgesic effect of intravenous acetaminophen with that of flurbiprofen axetil on post-breast surgery pain: a randomized controlled trial. J Anesth. 2016;30(3):405–9.

    Article  PubMed  Google Scholar 

  77. Kang JE, Park SK, Song IK, Lee JH, Kim JT, Kim HS. Comparison of the efficacy and safety of different doses of propacetamol for postoperative pain control after breast surgery. Pain Manag Nurs. 2015;16(3):367–71.

    Article  PubMed  Google Scholar 

  78. Priya V, Divatia JV, Sareen R, Upadhye S. Efficacy of intravenous ketoprofen for pre-emptive analgesia. J Postgrad Med. 2002;48(2):109–12.

    CAS  PubMed  Google Scholar 

  79. Kampe S, Warm M, Landwehr S, Dagtekin O, Haussmann S, Paul M, et al. Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer. Curr Med Res Opin. 2006;22(10):1949–54.

    Article  CAS  PubMed  Google Scholar 

  80. Mitchell A, McCrea P, Inglis K, Porter G. A randomized, controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine (Tylenol 3) after outpatient breast surgery. Ann Surg Oncol. 2012;19(12):3792–800.

    Article  PubMed  Google Scholar 

  81. Na HS, Oh AY, Koo BW, Lim DJ, Ryu JH, Han JW. Preventive analgesic efficacy of nefopam in acute and chronic pain after breast cancer surgery: a prospective, double-blind, and randomized trial. Medicine. 2016;95(20):e3705.

  82. • Kim SH, Oh YJ, Park BW, Sim J, Choi YS. Effects of single-dose dexmedetomidine on the quality of recovery after modified radical mastectomy: a randomised controlled trial. Minerva anesthesiologica. 2013;79(11):1248-58. This RCT demonstrated that patients who received a single dose of dexmedetomidine intraoperatively had significantly higher QoR-40 scores and significantly reduced opioid requirement postoperatively. The bolus was also effective in lowering the incidence of PONV.

  83. Das R, Das RK, Sahoo S, Nanda S. Role of dexmedetomidine as an anaesthetic adjuvant in breast cancer surgery as a day-care procedure: a randomised controlled study. Indian J Anaesth. 2018;62(3):182–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mohamed SA, Abdel-Ghaffar HS, Hassan NA, El Sherif FA, Shouman SA, Omran MM, Hassan SB, Allam AAAE, Sayed DG. Pharmacokinetics and pharmacodynamics of 3 doses of oral-mucosal dexmedetomidine gel for sedative premedication in women undergoing modified radical mastectomy for breast cancer. Anesth Analg. 2021;132(2):456–64.

    Article  CAS  PubMed  Google Scholar 

  85. Oddby-Muhrbeck E, Eksborg S, Bergendahl HT, Muhrbeck O, Lönnqvist PA. Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery. Anesthesiology. 2002;96(5):1109–14.

    Article  CAS  PubMed  Google Scholar 

  86. Wong CS, Wu CT, Yu JC, Yeh CC, Lee MM, Tao PL. Preincisional dextromethorphan decreases postoperative pain and opioid requirement after modified radical mastectomy. Can J Anesth. 1999;46(12):1122–6.

    Article  CAS  PubMed  Google Scholar 

  87. Eisenberg E, Pud D, Koltun L, Loven D. Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study. J Pain. 2007;8(3):223–9.

    Article  CAS  PubMed  Google Scholar 

  88. Adam F, Libier M, Oszustowicz T, Lefebvre D, Beal J, Meynadier J. Preoperative small-dose ketamine has no preemptive analgesic effect in patients undergoing total mastectomy. Anesth Analg. 1999;89(2):444–7.

    Article  CAS  PubMed  Google Scholar 

  89. Nayak BM, Misra S, Mitra JK, Sahoo AK. Effect of preoperative subanaesthetic ketamine on postoperative pain in women undergoing modified radical mastectomy: a randomised control trial. Eur J Anaesthesiol. 2021;38(5):556–8.

    Article  PubMed  Google Scholar 

  90. Kang C, Cho AR, Kim KH, Lee EA, Lee HJ, Kwon JY, Kim H, Kim E, Baik JS, Kim C. Effects of intraoperative low-dose ketamine on persistent postsurgical pain after breast cancer surgery: a prospective, randomized, controlled, double-blind study. Pain Physician. 2020;23(1):37–47.

    PubMed  Google Scholar 

  91. Morel V, Joly D, Villatte C, Dubray C, Durando X, Daulhac L, Coudert C, Roux D, Pereira B, Pickering G. Memantine before mastectomy prevents post-surgery pain: a randomized, blinded clinical trial in surgical patients. PLoS One. 2016;11(4):e0152741.

  92. Fassoulaki A, Sarantopoulos C, Melemeni A, Hogan Q. EMLA reduces acute and chronic pain after breast surgery for cancer. Reg Anes Pain Med. 2000;25(4):350–5.

    Article  CAS  Google Scholar 

  93. Akan A, Eryavuz Y, Kamali S, Simşek S, Hot S, Bademci R. A randomized, placebo controlled study: EMLA in minor breast surgery. Minerva Chir. 2012;67(2):181–5.

    CAS  PubMed  Google Scholar 

  94. Couceiro TC, Lima LC, Burle LM, Valença MM. Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial. Braz J Anesthesiol. 2015;65(3):207–12. https://doi.org/10.1016/j.bjane.2014.05.017.

    Article  PubMed  Google Scholar 

  95. •• Kendall MC, McCarthy RJ, Panaro S, Goodwin E, Bialek JM, Nader A, De Oliveira GS Jr. The effect of intraoperative systemic lidocaine on postoperative persistent pain using initiative on methods, measurement, and pain assessment in clinical trials criteria assessment following breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Pain Pract. 2018;18(3):350-359. Although other studies showed that intravenous lidocaine did not significantly reduce acute postoperative pain for breast surgery, this RCT demonstrated that the reported incidence of persistent pain at 6 months after breast cancer surgery was significantly lower in the group that received lidocaine bolus plus infusion during surgery.

  96. Khan JS, Hodgson N, Choi S, Reid S, Paul JE, Hong NJL, Holloway C, Busse JW, Gilron I, Buckley DN, McGillion M, Clarke H, Katz J, Mackey S, Avram R, Pohl K, Rao-Melacini P, Devereaux PJ. Perioperative pregabalin and intraoperative lidocaine infusion to reduce persistent neuropathic pain after breast cancer surgery: a multicenter, factorial, randomized, controlled pilot trial. J Pain. 2019;20(8):980–93.

    Article  CAS  PubMed  Google Scholar 

  97. Grigoras A, Lee P, Sattar F, Shorten G. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. Clin J Pain. 2012;28(7):567–72.

    Article  PubMed  Google Scholar 

  98. Gomez-Hernandez J, Orozco-Alatorre AL, Dominguez-Contreras M, Oceguera-Villanueva A, Gomez-Romo S, Alvarez Villasenor AS, et al. Preoperative dexamethasone reduces postoperative pain, nausea and vomiting following mastectomy for breast cancer. BMC Cancer. 2010;10(1):692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. •• Cortés-Flores AO, Jiménez-Tornero J, Morgan-Villela G, Delgado-Gómez M, Zuloaga-Fernández Del Valle CJ, García-Rentería J, Rendón-Félix J, Fuentes-Orozco C, Macías-Amezcua MD, Ambriz-González G, Alvarez-Villaseñor AS, Urias-Valdez D, Chavez-Tostado M, Contreras-Hernández GI, González-Ojeda A. Effects of preoperative dexamethasone on postoperative pain, nausea, vomiting and respiratory function in women undergoing conservative breast surgery for cancer: results of a controlled clinical trial. Eur J Cancer Care (Engl). 2018;27(1). Dexamethasone 8 mg was shown to be effective in reducing postoperative pain scores and frequency of nausea/vomiting for patients undergoing partial mastectomy at 1 h, 6 h, 12 h, and 24 h postoperatively compared to placebo.

  100. Olanders KJ, Lundgren GA, Johansson AM. Betamethasone in prevention of postoperative nausea and vomiting following breast surgery. J Clin Anesth. 2014;26(6):461–5.

    Article  CAS  PubMed  Google Scholar 

  101. Hval K, Thagaard KS, Schlichting E, Raeder J. The prolonged postoperative analgesic effect when dexamethasone is added to a nonsteroidal antiinflammatory drug (rofecoxib) before breast surgery. Anesth Analg. 2007;105(2):481–6.

    Article  CAS  PubMed  Google Scholar 

  102. Steinthorsdottir KJ, Awada HN, Abildstrøm H, Kroman N, Kehlet H, Aasvang EK. Dexamethasone dose and early postoperative recovery after mastectomy: a double-blind, randomized trial. Anesthesiology. 2020;132(4):678–91.

    Article  PubMed  Google Scholar 

  103. Wattwil M, Thörn SE, Lövqvist A, Wattwil L, Gupta A, Liljegren G. Dexamethasone is as effective as ondansetron for the prevention of postoperative nausea and vomiting following breast surgery. Acta Anaesthesiol Scand. 2003;47(7):823–7.

    Article  CAS  PubMed  Google Scholar 

  104. Romundstad L, Breivik H, Roald H, Skolleborg K, Haugen T, Narum J, et al. Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation surgery: a single-dose, randomized, parallel-group study with methylprednisolone 125 mg, parecoxib 40 mg, and placebo. Anesth Analg. 2006;102(2):418–25.

    Article  CAS  PubMed  Google Scholar 

  105. Grover VK, Mathew PJ, Yaddanapudi S, Sehgal S. A single dose of preoperative gabapentin for pain reduction and requirement of morphine after total mastectomy and axillary dissection: randomized placebo-controlled double-blind trial. J Postgrad Med. 2009;55(4):257–60.

    Article  CAS  PubMed  Google Scholar 

  106. Fassoulaki A, Triga A, Melemeni A, Sarantopoulos C. Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer. Anesth Analg. 2005;101(5):1427–32.

    Article  CAS  PubMed  Google Scholar 

  107. Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Anesth Analg. 2002;95(4):985–91.

    Article  CAS  PubMed  Google Scholar 

  108. Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger H, Dahl JB. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology. 2002;97(3):560–4.

    Article  CAS  PubMed  Google Scholar 

  109. Bharti N, Bala I, Narayan V, Singh G. Effect of gabapentin pretreatment on propofol consumption, hemodynamic variables, and postoperative pain relief in breast cancer surgery. Acta Anaesthesiol Taiwan. 2013;51(1):10–3.

    Article  PubMed  Google Scholar 

  110. Mansor SH, Choy CY. Effect of preoperative oral pregabalin on postoperative pain after mastectomy. Middle East J Anesthesiol. 2015;23(1):63–8.

    PubMed  Google Scholar 

  111. Kim SY, Song JW, Park B, Park S, An YJ, Shim YH. Pregabalin reduces post-operative pain after mastectomy: a double-blind, randomized, placebo-controlled study. Acta Anaesthesiol Scand. 2011;55(3):290–6.

    Article  CAS  PubMed  Google Scholar 

  112. Freedman BM, O’Hara E. Pregabalin has opioid-sparing effects following augmentation mammaplasty. Aesthetic Surg J. 2008;28(4):421–4.

    Article  Google Scholar 

  113. Mir A, Mohebbi N, Omranipour R, Sedaghat M, Lashkari M, Masoomzadeh M. Study of pregabalin effect on postsurgical pain in breast cancer patients: a double-blind randomized clinical trial using placebo. Breast J. 2020;26(11):2286–8.

    Article  PubMed  Google Scholar 

  114. Hetta DF, Mohamed MA, Mohammad MF. Analgesic efficacy of pregabalin in acute postmastectomy pain: placebo controlled dose ranging study. J Clin Anesth. 2016;34:303–9.

    Article  CAS  PubMed  Google Scholar 

  115. Doha NM, Rady A, Azab SR. Preoperative use of gabapentin decreases the anesthetic and analgesic requirements in patients undergoing radical mastectomy. Egyptian Journal of Anaesthesia. 2010;26(4):287–91.

    Article  Google Scholar 

  116. Azemati S, Dokouhaki AG, Talei A, Khademi S, Moin-Vaziri N. Evaluation of the effect of a preoperative single dose of gabapentin on emergence agitation in patients undergoing breast cancer surgery. Middle East Journal of Cancer. 2013;4(4):145–51.

    Google Scholar 

  117. Reyad RM, Omran AF, Abbas DN, Kamel MA, Shaker EH, Tharwat J, Reyad EM, Hashem T. The possible preventive role of pregabalin in postmastectomy pain syndrome: a double-blinded randomized controlled trial. J Pain Symptom Manag. 2019;57(1):1–9.

    Article  Google Scholar 

  118. Hetta DF, Elgalaly NA, Hetta HF, Fattah Mohammad MA. Preoperative duloxetine to improve acute pain and quality of recovery in patients undergoing modified radical mastectomy: a dose-ranging randomized controlled trial. J Clin Anesth. 2020;67:110007.

  119. Jacobs A, Lemoine A, Joshi GP, Van de Velde M, Bonnet F. PROSPECT guideline for oncological breast surgery: a systematic review and procedure-specific postoperative pain management recommendations. Anaesthesia. 2020;75(5):664–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Zhao-Fleming H, Hand A, Zhang K, Polak R, Northcut A, Jacob D, Dissanaike S, Rumbaugh KP. Effect of non-steroidal anti-inflammatory drugs on post-surgical complications against the backdrop of the opioid crisis. Burns Trauma. 2018;6:25.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Sheth KR, Bernthal NM, Ho HS, Bergese SD, Apfel CC, Stoicea N, Jahr JS. Perioperative bleeding and non-steroidal anti-inflammatory drugs: An evidence-based literature review, and current clinical appraisal. Medicine. 2020;99(31):e20042.

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Columbia University, 622 West 168th Street, PH505, NY, 10032, New York, USA

    Robert B. Maniker

  2. New York Presbyterian Hospital, New York, NY, USA

    James Damiano & Martin Pavelic

  3. Oregon Health and Science University, Portland, OR, USA

    Ryan M. J. Ivie & Glenn E. Woodworth

Authors
  1. Robert B. Maniker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Damiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryan M. J. Ivie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Pavelic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Glenn E. Woodworth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert B. Maniker.

Ethics declarations

Conflict of Interest

Robert Maniker declares no conflicts of interest. James Damiano declares no conflicts of interest. Ryan Ivie declares no conflicts of interest. Martin Pavelic declares no conflicts of interest. Glenn Woodworth declares no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Acute Pain Medicine

Presentations: This work has not been presented or published.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 33 kb)

Supplementary file2 (DOCX 61 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maniker, R.B., Damiano, J., Ivie, R.M.J. et al. Perioperative Breast Analgesia: a Systematic Review of the Evidence for Perioperative Analgesic Medications. Curr Pain Headache Rep 26, 299–321 (2022). https://doi.org/10.1007/s11916-022-01031-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-022-01031-z

Keywords

Search

Navigation