Skip to main content
Top
Published in: Drugs & Aging 6/2019

01-06-2019 | Pharmacokinetics | Short Communication

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

Authors: Peter M. Odor, Alison G. Cavalier, Neal D. Reynolds, King S. Ang, Simon J. Parrington, Hua Xu, Atholl Johnston, Frederic J. Sage

Published in: Drugs & Aging | Issue 6/2019

Login to get access

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).
Literature
1.
go back to reference 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.PubMed 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.PubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference Abernethy D, Greenblatt D. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol. 1983;5:1093–6.CrossRefPubMed Abernethy D, Greenblatt D. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol. 1983;5:1093–6.CrossRefPubMed
5.
go back to reference Muravchick S. Geroanesthesia: principles for the management of the elderly patient. St. Louis: Mosby; 1997. p. 306. Muravchick S. Geroanesthesia: principles for the management of the elderly patient. St. Louis: Mosby; 1997. p. 306.
6.
go back to reference Muravchick S. The aging process: anesthetic implications. Acta Anaesthesiol Belg. 1998;49:85–90.PubMed Muravchick S. The aging process: anesthetic implications. Acta Anaesthesiol Belg. 1998;49:85–90.PubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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. 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.
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59:551–79.CrossRefPubMed Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59:551–79.CrossRefPubMed
16.
go back to reference Sanford M, Keating G. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010;70:761–91.CrossRefPubMed Sanford M, Keating G. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010;70:761–91.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference Doyle E, Morton N, McNicol L. Plasma bupivacaine levels after fascia iliaca block with and without adrenaline. Paediatr Anaesth. 1997;7:121–4.CrossRefPubMed Doyle E, Morton N, McNicol L. Plasma bupivacaine levels after fascia iliaca block with and without adrenaline. Paediatr Anaesth. 1997;7:121–4.CrossRefPubMed
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference Kopacz DJ, Allen HW. Accidental intravenous levobupivacaine. Anesth Analg. 1999;89:1027–9.PubMed Kopacz DJ, Allen HW. Accidental intravenous levobupivacaine. Anesth Analg. 1999;89:1027–9.PubMed
21.
go back to reference Pirotta D, Spriqqe J. Convulsions following axillary brachial plexus blockade with levobupivacaine. Anaesthesia. 2002;57:1187–9.CrossRefPubMed Pirotta D, Spriqqe J. Convulsions following axillary brachial plexus blockade with levobupivacaine. Anaesthesia. 2002;57:1187–9.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg. 2003;96:1188–90.CrossRefPubMed Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg. 2003;96:1188–90.CrossRefPubMed
24.
go back to reference 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.PubMed 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.PubMed
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Safety and Pharmacokinetics of Levobupivacaine Following Fascia Iliaca Compartment Block in Elderly Patients
Authors
Peter M. Odor
Alison G. Cavalier
Neal D. Reynolds
King S. Ang
Simon J. Parrington
Hua Xu
Atholl Johnston
Frederic J. Sage
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 6/2019
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-019-00652-1

Other articles of this Issue 6/2019

Drugs & Aging 6/2019 Go to the issue