Advertisement

Safety and Pharmacokinetics of Levobupivacaine Following Fascia Iliaca Compartment Block in Elderly Patients

  • Peter M. OdorEmail author
  • Alison G. Cavalier
  • Neal D. Reynolds
  • King S. Ang
  • Simon J. Parrington
  • Hua Xu
  • Atholl Johnston
  • Frederic J. Sage
Short Communication

Abstract

Background

Fascia iliaca compartment block (FICB) is an increasingly popular analgesic technique in elderly patients with hip fracture. Despite requiring large volumes of local anaesthetic, there are no plasma pharmacokinetic data on FICB in elderly patients.

Objectives

The objective of this study was to determine the pharmacokinetic profile of a levobupivacaine 75 mg (30 mL 0.25%) FICB dose in patients aged ≥ 80 years with fractured femur.

Methods

This was a single-arm descriptive pilot study. Twelve adults aged ≥ 80 years with hip fracture received FICB performed under ultrasound guidance. Venous blood was sampled at 10, 20, 30, 45, 60, 75, 90, 105, 120 and 240 min after injection. Total plasma levobupivacaine concentration was measured by mass spectrometry. The main outcome measures were pharmacokinetic parameters, including maximum observed plasma concentration (Cmax), time to reach Cmax (tmax) and area under the plasma concentration–time curve.

Results

The median (interquartile range [IQR]) Cmax was 0.82 μg/mL (0.47–1.03). tmax was 45 min (41:20–60:00). No evidence of toxicity was identified. Plasma levobupivacaine concentrations were below the threshold associated with toxicity in younger, healthy patients (2.6 μg/mL). No association was found between individual patient Cmax and α1-acid glycoprotein, weight or body mass index, although the study was not powered for these outcomes.

Conclusions

Absorption of levobupivacaine was slow and all patients had plasma concentrations below the toxic threshold. This pharmacokinetic analysis concludes that the technique appears to be well-tolerated and efficacious at reducing pain and is associated with systemic plasma concentrations unlikely to be associated with major adverse effects in elderly patients.

Clinical Trial Registration

ISRCTN27364035 (UK Clinical Trials Gateway).

Notes

Acknowledgements

We wish to thank Toqa El-Nahhas for her assistance in processing the blood sample analysis at the Analytic Services International Laboratory.

Compliance with Ethical Standards

Funding

This study was supported by a National Institute of Academic Anaesthesia (NIAA) and Regional Anaesthesia-UK (RA-UK) research grant.

Conflict of interest

Atholl Johnston is the Facility Director at Analytical Services International Ltd, St George’s University of London, where all sample analysis was conducted. Peter M. Odor, Alison G. Cavalier, Neal D. Reynolds, King S. Ang, Simon J. Parrington, Hua Xu and Frederic J. Sage declare no conflicts of interest related to this study.

Ethical approval

The study was approved by the London – Central Research Ethics Committee (REC reference 16/LO/1321) and Health Research Authority. The study was conducted according to the Helsinki Declaration, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice recommendations and applicable local regulations.

Informed consent

Written informed consent was received from all subjects prior to the conduct of any study-related procedures.

References

  1. 1.
    Dalens B, Vanneuville G, Tanguy A. Comparison of the fascia iliaca compartment block with the 3-in-1 block in children. Anesth Analg. 1989;69:705–13.Google Scholar
  2. 2.
    Foss N, Kristensen BB, Bundgaard M, et al. Fascia iliaca compartment blockade for acute pain control in hip fracture patients: a randomized, placebo-controlled trial. Anesthesiology. 2007;106:773–8.CrossRefGoogle Scholar
  3. 3.
    National Institute for Health and Care Excellence. Clinical guideline 124: the management of hip fracture in adults, 2011. https://www.nice.org.uk/guidance/cg124. Accessed 26 Sep 2018.
  4. 4.
    Abernethy D, Greenblatt D. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol. 1983;5:1093–6.CrossRefGoogle Scholar
  5. 5.
    Muravchick S. Geroanesthesia: principles for the management of the elderly patient. St. Louis: Mosby; 1997. p. 306.Google Scholar
  6. 6.
    Muravchick S. The aging process: anesthetic implications. Acta Anaesthesiol Belg. 1998;49:85–90.Google Scholar
  7. 7.
    Simon MJ, Veering BT, Stienstra R, van Kleef JW, Burm AG. Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration. Br J Anaesth. 2004;93:512–20.CrossRefGoogle Scholar
  8. 8.
    Warman P, Conn D, Nicholls B, Wilkinson D, editors. Regional anaesthesia, stimulation and ultrasound techniques. Oxford specialist handbooks in anaesthesia series. Oxford: Oxford University Press; 2014. pp. 418–9.Google Scholar
  9. 9.
    Newman B, McCarthy L, Thomas PW, May P, Layzell M, Horn K. A comparison of pre-operative nerve stimulator-guided femoral nerve block and fascia iliaca compartment block in patients with a femoral neck fracture. Anaesthesia. 2013;68:899–903.CrossRefGoogle Scholar
  10. 10.
    Haines L, Dickman E, Ayvazyan S, et al. Ultrasound-guided fascia iliaca compartment block for hip fractures in the emergency department. J Emerg Med. 2012;43:692–7.CrossRefGoogle Scholar
  11. 11.
    Godoy Monzón D, Iserson KV, Vazquez JA. Single fascia iliaca compartment block for post-hip fracture pain relief. J Emerg Med. 2007;32:257–62.CrossRefGoogle Scholar
  12. 12.
    New York School of Regional Anaesthesia. Ultrasound-guided fascia iliaca block. 2013. https://www.nysora.com/ultrasound-guided-fascia-iliaca-block-2. Accessed 26 Sep 2018.
  13. 13.
    Stevens M, Harrison G, McGrail M. A modified fascia iliaca compartment block has significant morphine-sparing effect after total hip arthroplasty. Anaesth Intensive Care. 2007;35:949–52.CrossRefGoogle Scholar
  14. 14.
    Proost JH, Meijer DKW. MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring. Comp Biol Med. 1992;22:155–62.CrossRefGoogle Scholar
  15. 15.
    Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59:551–79.CrossRefGoogle Scholar
  16. 16.
    Sanford M, Keating G. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010;70:761–91.CrossRefGoogle Scholar
  17. 17.
    Paut O, Schreiber E, Meyrieux V, et al. High plasma ropivacaine concentrations after fascia iliaca compartment block in children. Br J Anaesth. 2004;92:416–8.CrossRefGoogle Scholar
  18. 18.
    Doyle E, Morton N, McNicol L. Plasma bupivacaine levels after fascia iliaca block with and without adrenaline. Paediatr Anaesth. 1997;7:121–4.CrossRefGoogle Scholar
  19. 19.
    Snoeck MM, Vree TB, Gielen MJ. Steady state bupivacaine plasma concentrations and safety of a femoral “3-in-1” nerve block with bupivacaine in patients over 80 years of age. Int J Clin Pharmacol Ther. 2003;41:107–13.CrossRefGoogle Scholar
  20. 20.
    Kopacz DJ, Allen HW. Accidental intravenous levobupivacaine. Anesth Analg. 1999;89:1027–9.Google Scholar
  21. 21.
    Pirotta D, Spriqqe J. Convulsions following axillary brachial plexus blockade with levobupivacaine. Anaesthesia. 2002;57:1187–9.CrossRefGoogle Scholar
  22. 22.
    Khan H, Atanassoff PG. Accidental intravascular injection of levobupivacaine and lidocaine during the transarterial approach to the axillary brachial plexus [letter]. Can J Anaesth. 2003;50:95.CrossRefGoogle Scholar
  23. 23.
    Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg. 2003;96:1188–90.CrossRefGoogle Scholar
  24. 24.
    Breslin DS, Martin G, Macleod DB, D’ercole F, Grant SA. Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: a report of two cases. Reg Anesth Pain Med. 2003;28:144–7.Google Scholar
  25. 25.
    Knudsen K, Suurküla B, Blomberg S, Sjövall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth. 1997;78:507–14.CrossRefGoogle Scholar
  26. 26.
    Gristwood R, Bardsley H, Baker H, Dickens J. Reduced cardiotoxicity of levobupivacaine compared with racemic bupivacaine (Marcaine): new clinical evidence. Expert Opin Investig Drugs. 1994;3:1209–12.CrossRefGoogle Scholar
  27. 27.
    Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol. 1998;46:245–9.CrossRefGoogle Scholar
  28. 28.
    Karmakar MK, Ho AM, Law BK, Wong AS, Shafer SL, Gin T. Arterial and venous pharmacokinetics of ropivacaine with and without epinephrine after thoracic paravertebral block. Anesthesiology. 2005;103:704–11.CrossRefGoogle Scholar
  29. 29.
    Rettig HC, Lerou JG, Gielen MJ, Boersma E, Burm AG. The pharmacokinetics of ropivacaine after four different techniques of brachial plexus blockade. Anaesthesia. 2007;62:1008–14.CrossRefGoogle Scholar
  30. 30.
    Griffiths JD, Barron FA, Grant S, Bjorksten AR, Hebbard P, Royse CF. Plasma ropivacaine concentrations after ultrasound-guided transversus abdominis plane block. Br J Anaesth. 2010;105:853–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of AnaesthesiaSt. George’s University HospitalLondonUK
  2. 2.Department of AnaesthesiaEast Surrey HospitalSurreyUK
  3. 3.Analytical Services InternationalSt. George’s University of LondonLondonUK
  4. 4.Department of Clinical Pharmacology, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK

Personalised recommendations