Download PDF
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53(10): 704-717
DOI: 10.1055/s-0043-104600
CME-Fortbildung
Georg Thieme Verlag KG Stuttgart · New York

Schmerztherapeutische Aspekte bei Tumoroperationen

Pain Therapy Aspects in Tumour Surgery
Stefan Wirz
,
Michael Schenk
,
Kristin Kieselbach
Further Information

Publication History

Publication Date:
13 November 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Trotz einer Vielzahl von Therapieoptionen wird die Akutschmerztherapie nach onkologischen Operationen häufig als unzureichend beschrieben. Neben einer unzureichenden Akutschmerztherapie können weitere Faktoren eine Hypersensitivierung und Chronifizierung sowie den Verlauf der Tumorerkrankung beeinflussen. Dieser Beitrag erklärt pathophysiologische Hintergründe und erläutert geeignete Therapiemodalitäten.

Abstract

Due to preexisting pain or surgically induced sensitization patients undergoing oncological surgery are predisposed for a postoperative high pain intensity with the risk of developing persistent pain. In oncological surgery, pain therapy should be adapted to the underlying pain mechanism. Different treatment principles should be applied in a graded concept of acute pain therapy. The rationale implies the “conventional” use of the WHO step scheme, the administration of opioids as PCA as well as regional analgesia and agents with anti-hypersensitizing properties. Anti-hypersensitizing and anti-neuropathic treatment principles may include the use of antidepressants, anticonvulsants, intravenous lidocaine and s-ketamine. Before using such treatment, pain mechanisms should be verified by an adequate pain diagnostic. The impact of perioperative regional analgesia on the oncological outcome is subject to controversy. Opioids reveal both: tumor promoting and tumor inhibiting properties.

Kernaussagen

  • Tumorchirurgisch behandelte Patienten sind wegen vorbestehender oder perioperativ bedingter Sensitivierungsmechanismen hinsichtlich einer hohen postoperativen Schmerzintensität und der Gefahr der Schmerzpersistenz mit Chronifizierung besonders prädisponiert.

  • Die Schmerztherapie bei onkologischen Operationen sollte entsprechend einer Analyse der den Schmerzen zugrunde liegenden Mechanismen erfolgen und in einem abgestuften Konzept unter Einbeziehung verschiedener Wirkprinzipien durchgeführt werden. So erscheint neben der „konventionellen“ Anwendung von Stufe-1- bis -3-Substanzen, der PCIA-Technik mit Opioiden und regionalen Schmerztherapieverfahren die Anwendung antihypersensitivierender Substanzen sinnvoll.

  • Zur Behandlung der Hypersensitivierungsmechanismen sowie bei neuropathischen Schmerzen können Antidepressiva, Antikonvulsiva, intravenöses Lidocain und S-Ketamin eingesetzt werden. Zuvor sollte aber eine entsprechende Schmerzdiagnostik diese Schmerzmechanismen eindeutig nachgewiesen haben.

  • Der Einfluss der perioperativ eingesetzten Regionalanästhesie auf den weiteren Tumorerkrankungsverlauf wird kontrovers diskutiert.

  • Opioide weisen sowohl tumorhemmende als auch tumorfördernde Eigenschaften auf.

Schlüsselwörter

Tumortherapie - Tumorchirurgie - Analgesie - Schmerztherapie - Opioide - regionale Anästhesie

Key words

tumor pain - analgesia - anti-hypersensitizing - regional anaesthesia - opioids
 

  • Literatur

  • 1 Centers for Disease Control and Prevention (CDC). Leading causes of death 2015. Im Internet: https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm Stand: 14.08.2018
    PubMedGoogle Scholar
  • 2 World Health Organisation (WHO), Regional Office for Europe. Leading causes of death in Europe 2012. http://www.euro.who.int/__data/assets/pdf_file/0004/185215/Leading-causes-of-death-in-Europe-Fact-Sheet.pdf Stand: 14.08.2018
    PubMedGoogle Scholar
  • 3 Wang L, Guyatt GH, Kennedy SA. et al. Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies. CMAJ 2016; 188: E352-E361
    CrossrefPubMedGoogle Scholar
  • 4 Häuser W, Schmutzer G, Brähler E. Chronische Schmerzen, Schmerzkrankheit und Zufriedenheit der Betroffenen mit der Schmerzbehandlung in Deutschland. Ergebnisse einer repräsentativen Bevölkerungsstichprobe. Schmerz 2014; 28: 259-264
    CrossrefPubMedGoogle Scholar
  • 5 Valeberg BT, Rustoen T, Bjordal K. et al. Self-reported prevalence, etiology, and characteristics of pain in oncology outpatients. Eur J Pain 2008; 12: 582-590
    CrossrefPubMedGoogle Scholar
  • 6 Wirz S, Schenk M, Kleinmann B, Kieseritzky K. Chronifizierungsmechanismen und Abhängigkeitspotenziale bei Tumorschmerz. Vergleich mit Nichttumorschmerz – eine Literaturübersicht. Schmerz 2016; 30: 510-518
    CrossrefPubMedGoogle Scholar
  • 7 Schmidt BL. The Neurobiology of Cancer Pain. J Oral Maxillofac Surg 2015; 73 (Suppl. 12) 132-135
    CrossrefPubMedGoogle Scholar
  • 8 Carvalho B, Clark DJ, Angst MS. Local and systemic release of cytokines, nerve growth factor, prostaglandin E2, and substance P in incisional wounds and serum following cesarean delivery. J Pain 2008; 9: 650-657
    CrossrefPubMedGoogle Scholar
  • 9 Kehlet H, Jensen TS, Woolf CJ. Persistent surgical pain: risk factors and prevention. Lancet 2006; 367: 1618-1625
    CrossrefPubMedGoogle Scholar
  • 10 Schnabel A, Pogatzki-Zahn E. Prädiktoren für chronische Schmerzen nach Operationen. Was wissen wir wirklich?. Schmerz 2010; 24: 517-531
    CrossrefPubMedGoogle Scholar
  • 11 Torres Lacomba M, Mayoral del Moral O, Coperias Zazo JL. et al. Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study. Clin J Pain 2010; 26: 320-325
    CrossrefPubMedGoogle Scholar
  • 12 Zaza C, Baine N. Cancer pain and psychosocial factors: a critical review of the literature. J Pain Symptom Manage 2002; 24: 526-542
    CrossrefPubMedGoogle Scholar
  • 13 Green CR, Hart-Johnson T, Loeffler DR. Cancer-related chronic pain: examining quality of life in diverse cancer survivors. Cancer 2011; 117: 1994-2003
    CrossrefPubMedGoogle Scholar
  • 14 Lu Q, Krull KR, Leisenring W. et al. Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study. Pain 2011; 152: 2616-2624
    CrossrefPubMedGoogle Scholar
  • 15 Joshi GP, Jaschinski T, Bonnet F, Kehlet H. PROSPECT collaboration. Optimal pain management for radical prostatectomy surgery: what is the evidence?. BMC Anesthesiol 2015; 15: 15
    CrossrefPubMedGoogle Scholar
  • 16 Cheng GS, Ilfeld BM. A review of postoperative analgesia for breast cancer surgery. Pain Manag 2016; 6: 603-618
    CrossrefPubMedGoogle Scholar
  • 17 Capdevila X, Barthelet Y, Biboulet P. et al. Effects of Perioperative Analgesic Technique on the Surgical Outcome and Duration of Rehabilitation after Major Knee Surgery. Anesthesiology 1999; 91: 8-15
    CrossrefPubMedGoogle Scholar
  • 18 Parikh RP, Sharma K, Guffey R, Myckatyn TM. Preoperative Paravertebral Block Improves Postoperative Pain Control and Reduces Hospital Length of Stay in Patients Undergoing Autologous Breast Reconstruction after Mastectomy for Breast Cancer. Ann Surg Oncol 2016; 23: 4262-4269
    CrossrefPubMedGoogle Scholar
  • 19 McNicol ED, Ferguson MC, Hudcova J. Patient Controlled opioid analgesia versus non-patient controlled opioidanalgesia for postoperative pain. Cochrane Database Syst Rev 2015; (06) CD003348
    PubMedGoogle Scholar
  • 20 Chou R, Gordon DB, de Leon-Casasola OA. et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologistsʼ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain 2016; 17: 131-157
    CrossrefPubMedGoogle Scholar
  • 21 Dauri M, Faria S, Gatti A. et al. Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Curr Drug Targets 2009; 10: 716-733
    CrossrefPubMedGoogle Scholar
  • 22 Finnerup NB, Attal N, Haroutounian S. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162-173
    CrossrefPubMedGoogle Scholar
  • 23 Kendall MC, McCarthy RJ, Panaro S. et al. The Effect of Intraoperative Systemic Lidocaine on Postoperative Persistent Pain Using IMMPACT Criteria Assessment Following Breast Cancer Surgery: A Randomized, Double-blind Placebo Controlled Trial. Pain Pract 2018; 18: 350-359
    CrossrefPubMedGoogle Scholar
  • 24 Kim JE, Choi JB, Koo BN. et al. Efficacy of Intravenous Lidocaine During Endoscopic Submucosal Dissection for Gastric Neoplasm: A Randomized, Double-Blind, Controlled Study. Medicine (Baltimore) 2016; 95: e3593
    PubMedGoogle Scholar
  • 25 Groudine SB, Fisher HAG, Kaufman jr. RP. et al. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg 1998; 86: 235-239
    PubMedGoogle Scholar
  • 26 Koppert W, Weigand M, Neumann F. et al. Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg 2004; 98: 1050-1055
    PubMedGoogle Scholar
  • 27 Kranke P, Jokinen J, Pace NL. et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev 2015; (07) CD009642
    PubMedGoogle Scholar
  • 28 Kollender Y, Bickels J, Stocki D. et al. Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients. Eur J Cancer 2008; 44: 954-962
    CrossrefPubMedGoogle Scholar
  • 29 Rakhman E, Shmain D, White I. et al. Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial. Clin Ther 2011; 33: 863-873
    CrossrefPubMedGoogle Scholar
  • 30 Snijdelaar DG, Cornelisse HB, Schmid RL, Katz J. A randomised, controlled study of peri-operative low dose s(+)-ketamine in combination with postoperative patient-controlled s(+)-ketamine and morphine after radical prostatectomy. Anaesthesia 2004; 59: 222-228
    CrossrefPubMedGoogle Scholar
  • 31 Elia N, Tramer MR. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain 2005; 113: 61-70
    CrossrefPubMedGoogle Scholar
  • 32 Koizuka S, Obata H, Sasaki M. et al. Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats. Can J Anesth 2005; 52 (05) 498-505
    CrossrefPubMedGoogle Scholar
  • 33 Blaudszun G, Lysakowski C, Elia N. et al. 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: 1312-1322
    CrossrefPubMedGoogle Scholar
  • 34 Brodner G, van Aken H. Does the choice of anaesthetic technique influence outcome?. Eur J Anaesthesiol 1998; 15: 740-747
    CrossrefPubMedGoogle Scholar
  • 35 Kehlet H, Jensen TS, Woolf CJ. Persistent surgical pain: risk factors and prevention. Lancet 2006; 367: 1618-1625
    CrossrefPubMedGoogle Scholar
  • 36 Tavare AN, Perry NJ, Benzonana LL. et al. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer 2012; 130: 1237-1250
    CrossrefPubMedGoogle Scholar
  • 37 Christopherson R, James KE, Tableman M. et al. Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia. Anesth Analg 2008; 107: 32532
    PubMedGoogle Scholar
  • 38 Gupta A, Björnsson A, Fredriksson M. et al. Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: A retrospective analysis of data from 655 patients in central Sweden. Br J Anaesth 2011; 107: 16470
    PubMedGoogle Scholar
  • 39 Bharati SJ, Chowdhury T, Bergese SD. et al. Anesthetics impact on cancer recurrence: What do we know?. J Cancer Res Ther 2016; 12: 464-468
    CrossrefPubMedGoogle Scholar
  • 40 Myles PS, Peyton P, Silbert B. et al. ANZCA Trials Group Investigators. Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence free survival: randomised trial. BMJ 2011; 342: d1491
    CrossrefPubMedGoogle Scholar
  • 41 Buggy DJ, Borgeat A, Cata J. et al. Consensus statement from The BJA Workshop on cancer and Anaesthesia. Br J Anaesth 2015; 114: 2-3
    CrossrefPubMedGoogle Scholar
  • 42 Bundscherer A, Malsy M, Gebhardt K. et al. Effects of ropivacaine, bupivacaine and sufentanil in colon and pancreatic cancer cells in vitro. Pharmacol Res 2015; 95 – 96: 126-131
    PubMedGoogle Scholar
  • 43 Dublin S, Walker RL, Jackson ML. et al. Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study. J Am Geriatr Soc 2011; 59: 1899-1907
    CrossrefPubMedGoogle Scholar
  • 44 Roy S, Wang J, Kelschenbach J. et al. Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol 2006; 1: 77-89
    CrossrefPubMedGoogle Scholar
  • 45 Pergolizzi J, Böger RH, Budd K. et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008; 8: 287-313
    CrossrefPubMedGoogle Scholar
  • 46 Idova GV, Alperina EL, Cheido MA. Contribution of brain dopamine, serotonin and opioid receptors in the mechanisms of neuroimmunomodulation: evidence from pharmacological analysis. Int Immunopharmacol 2012; 12: 618-625
    CrossrefPubMedGoogle Scholar
  • 47 Tegeder I, Grösch S, Schmidtko A. et al. G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: involvement of p 53 phosphorylation. Cancer Res 2003; 63: 1846-1852
    PubMedGoogle Scholar
  • 48 Koodie L, Yuan H, Pumper JA. et al. Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. Am J Pathol 2014; 184: 1073-1084
    CrossrefPubMedGoogle Scholar
  • 49 Khabbazi S, Nassar ZD, Goumon Y. et al. Morphine decreases the pro-angiogenic interaction between breast cancer cells and macrophages in vitro. Sci Rep 2016; 6: 31572
    CrossrefPubMedGoogle Scholar
  • 50 Lennon FE, Mirzapoiazova T, Mambetsariev B. et al. The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT) in human lung cancer. PLoS One 2014; 9: e91577
    CrossrefPubMedGoogle Scholar
  • 51 Hofbauer H, Schenk M, Kieselbach K. et al. Einsatz von Methadon zur Unterstützung der onkologischen Therapie? Eine Stellungnahme des Arbeitskreises Tumorschmerz der Deutschen Schmerzgesellschaft. Schmerz 2017; 31: 2-4
    CrossrefPubMedGoogle Scholar
  • 52 Suzuki M, Chiwaki F, Sawada Y. et al. Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo. PLoS One 2015; 10: e0123407
    CrossrefPubMedGoogle Scholar