A Pilot Study on the Addition of Tramadol or Eutectic Mixture of Local Anesthetics (Prilocaine Plus Lignocaine) to Local Lignocaine Infiltration for Prevention of Bone Marrow Aspiration/Biopsy Associated Pain

Abstract

Objectives Bone marrow aspiration although being a common procedure is associated with significant pain and its reduction remains an unmet need. We evaluated the use of tramadol and eutectic mixture of local anesthetics (prilocaine plus lignocaine) (EMLA) for reducing the severity of pain.

Materials and Methods In this pilot study, we compared the addition of either tramadol 50 mg per oral (T) or EMLA local application (E) or no intervention (L) in addition to the usual procedure of local infiltration with lignocaine 2% before bone marrow aspiration and biopsy (BMAB) in adults suspected/confirmed with malignancy. Both, tramadol and EMLA were administered 1 hour prior to the procedure. Primary end point was reduction in pain intensity with these interventions compared with local infiltration alone. Pain was assessed using numerical FACES pain scale, a visual analogue scale. Secondary end points were to see the effect on pre procedure apprehension and to find out the other factors associated with increased pain related to the procedure.

Statistical Analysis and Results A total of 300 patients were included in the study, 100 each in tramadol (T), EMLA (E), and only lignocaine local infiltration (L) arms, respectively. The mean pain intensity on the visual scale was significantly lower in the tramadol arm (T, E, L—3.4, 4.4, 4.7, respectively) (p < 0.0005). There was a significant reduction in percentage of patients who experienced moderate/severe pain (four or more) in the tramadol arm (T, E, L—45, 77, 82%, respectively) (p < 0.0005). Duration of procedure >10 minutes, body mass index >30, ECOG (Eastern Oncology Group) performance status ≥3, and age >50 years were positively correlated with more pain. Leukemia patients experienced significantly more pain compared with patients with lymphoma and other solid malignancies. Tramadol was well tolerated. No significant effect on pre-procedure apprehension was noted in any of the arms.

Conclusion Tramadol appears to have a preventive effect on bone marrow aspiration/biopsy-associated pain and appears to be well tolerated, whereas EMLA was not associated with such an effect. Larger studies may be done to ascertain the same.

Keywords

aspiration - bone marrow - EMLA - pain - tramadol

Publication History

Article published online:
11 November 2021

• References

• 1 Zahid MF. Methods of reducing pain during bone marrow biopsy: a narrative review. Ann Palliat Med 2015; 4 (04) 184-193
• 2 Gendron N, Zia Chahabi S, Poenou G. et al Pain assessment and factors influencing pain during bone marrow aspiration: a prospective study. PLoS One 2019; 14 (08) e0221534
• 3 Kuivalainen A-M. Pain and associated procedural anxiety in adults undergoing bone marrow aspiration and biopsy: therapeutic efficacy and feasibility of various analgesics. 2015. Available at: https://researchportal.helsinki.fi/en/publications/pain-and-associated-procedural-anxiety-in-adults-undergoing-bone-. Accessed December 5, 2019
• 4 Cerchione C, Martinelli G, Catalano L. et al Combined oral administration of analgesia and anxiolysis for pain associated with bone marrow aspiration and biopsy. J Clin Oncol 2019; 37 (Suppl. 15) e18313 DOI: 10.1200/JCO.2019.37.15_suppl.e18313.
• 5 Milligan DW, Howard MR, Judd A. Premedication with lorazepam before bone marrow biopsy. J Clin Pathol 1987; 40 (06) 696-698
• 6 Watmough S, Flynn M. A review of pain management interventions in bone marrow biopsy. J Clin Nurs 2011; 20 (5-6) 615-623
• 7 Buckley MM, Benfield P. Eutectic lidocaine/prilocaine cream. A review of the topical anaesthetic/analgesic efficacy of a eutectic mixture of local anaesthetics (EMLA). Drugs 1993; 46 (01) 126-151
• 8 Vanhelleputte P, Nijs K, Delforge M, Evers G, Vanderschueren S. Pain during bone marrow aspiration: prevalence and prevention. J Pain Symptom Manage 2003; 26 (03) 860-866
• 9 Talamo G, Liao J, Bayerl MG, Claxton DF, Zangari M. Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy. Support Care Cancer 2010; 18 (03) 301-305
• 10 Wolanskyj AP, Schroeder G, Wilson PR, Habermann TM, Inwards DJ, Witzig TE. A randomized, placebo-controlled study of outpatient premedication for bone marrow biopsy in adults with lymphoma. Clin Lymphoma 2000; 1 (02) 154-157
• 11 Dunlop TJ, Deen C, Lind S, Voyle RJ, Prichard JG, Use of combined oral narcotic and benzodiazepine for control of pain associated with bone marrow examination. South Med J. 1999 May;92(5):477-80. doi: 10.1097/00007611-199905000-00005. PMID: 10342892.
• 12 Holdsworth MT, Raisch DW, Winter SS. et al Pain and distress from bone marrow aspirations and lumbar punctures. Ann Pharmacother 2003; 37 (01) 17-22
• 13 Ng HN, Sim KM, Boey SK. Bone marrow harvesting using EMLA (eutectic mixture of local anaesthetics) cream, local anaesthesia and patient-controlled analgesia with alfentanil. Bone Marrow Transplant 1999; 23 (09) 941-945
• 14 Holdsworth MT, Raisch DW, Winter SS, et al. Pain and distress from bone marrow aspirations and lumbar punctures; 2003. Available at: https://journals.sagepub.com/doi/abs/10.1345/aph.1C088?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=aopd. Accessed December 7, 2019