the French Association of Regional Pharmacovigilance Centres
Original Research Article
Background: Some evidence of significant patient morbidity or mortality has been reported with the use of local anaesthetics (LAs). The most common adverse drug reactions (ADRs) to LAs are neurological (seizures) and cardiac (conduction disorders, cardiac arrests). However, little is known about other adverse drug reactions (ADRs).
Objective: The aim of this study was to characterize the safety profile of the LAs lidocaine, bupivacaine, mepivacaine, ropivacaine and levobupivacaine.
Study design: We studied ADRs occurring between 1995 and 2006 reported to the French Pharmacovigilance System.
Main outcome measure: For each ADR, we noted type of LA, type of ADR, its seriousness and the causality assessment score.
Results: We identified 727 reports (corresponding to 0.3% of patients in the database) in which LA was suspected as the cause of 1157 different ADRs. Sixty-one patients (8.7%) were children aged <18 years. Lidocaine (36.0%) and bupivacaine (35.4%) were the LAs most often involved. The most frequently reported ADRs were failure of the block (27.7%), followed by neurological (22.1%), allergic (19.4%) and cardiovascular (15.3%) complications. Eight patients died. Spinal anaesthesia performed with bupivacaine represented 90% of failed blocks. Seizures were the most frequent neurological complications, leading to death in four cases. Twenty-two of 111 cardiovascular complications were cardiac arrest (three of which were fatal).
Conclusion: To our knowledge, this is the first analysis of safety profiles of LAs in a non-selected population, using data collected in a pharmacovigilance database. The present study confirmed the frequency and seriousness of both neurological and cardiovascular complications. Other less well documented ADRs were identified, such as spinal anaesthesia failures with bupivacaine and allergic reactions following LA injections.
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
The authors acknowledge the assistance of all 31 regional centres of the French Pharmacovigilance System. They also want to thank Frédérique Martin, M.D. (Staff Anesthesiologist, Pôle d’Anesthésie Réanimation, Centre Hospitalier Universitaire Purpan, Faculté de Toulouse, Toulouse, France) for the linguistic consultation and correction of this article, and Philippe Cavalié (Agence Française de Sécurité Sanitaire des Produits de Santé, Saint Denis, France) for his valuable contribution. No funding was provided for the conduct of the study or preparation of the paper. There were no relevant conflicts of interest for any of the authors.
Clergue F, Auroy Y, Pequignot F, et al. French survey of anesthesia in 1996. Anesthesiology 1999 Nov; 91(5): 1509–20PubMedCrossRefGoogle Scholar
Enneking FK, Chan V, Greger J, et al. Lower-extremity peripheral nerve blockade: essentials of our current understanding. Reg Anesth Pain Med 2005 Jan; 30(1): 4–35PubMedGoogle Scholar
Fuzier R, Cuvillon P, Delcourt J, et al. Peripheral nerve block in orthopaedic surgery: multicentric evaluation of practicing professionnels and impact on the activity of the recovery room. Ann Fr Anesth Reanim 2007 Sep; 26(9): 761–8PubMedCrossRefGoogle Scholar
Hadzic A, Vloka JD, Kuroda MM, et al. The practice of peripheral nerve blocks in the United States: a national survey. Reg Anesth Pain Med 1998 May; 23(3): 241–6PubMedCrossRefGoogle Scholar
Klein SM, Pietrobon R, Nielsen KC, et al. Peripheral nerve blockade with long-acting local anesthetics: a survey of the Society for Ambulatory Anesthesia. Anesth Analg 2002 Jan; 94(1): 71–6PubMedGoogle Scholar
Horlocker TT, Neal JM. One hundred years later, I can still make your heart stop and your legs weak: the relationship between regional anesthesia and local anesthetic toxicity. Reg Anesth Pain Med 2002 Nov; 27(6): 543–4PubMedGoogle Scholar
Horlocker TT, McGregor DG, Matsushige DK, et al. A retrospective review of 4767 consecutive spinal anesthetics: central nervous system complications. Perioperative Outcomes Group. Anesth Analg 1997 Mar; 84(3): 578–84PubMedGoogle Scholar
Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: the SOS Regional Anesthesia Hotline Service. Anesthesiology 2002 Nov; 97(5): 1274–80PubMedCrossRefGoogle Scholar
De Tommaso O, Caporuscio A, Tagariello V. Neurological complications following central neuraxial blocks: are there predictive factors? Eur J Anaesthesiol 2002 Oct; 19(10): 705–16PubMedGoogle Scholar
Carpenter RL, Caplan RA, Brown DR, et al. Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992 Jun; 76(6): 906–16PubMedCrossRefGoogle Scholar
Bergman BD, Hebl JR, Kent J, et al. Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg 2003 Jan; 96(1): 247–52PubMedGoogle Scholar
Srinivasa V, Gerner P, Haderer A, et al. The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats. Anesth Analg 2003 Jul; 97(1): 91–5PubMedCrossRefGoogle Scholar
Borgeat A, Ekatodramis G, Kaberer F, et al. Acute and nonacute complications associated with interscalene block and shoulder surgery: a prospective study. Anesthesiology 2001 Oct; 95(4): 875–80PubMedCrossRefGoogle Scholar
Bisschop DY, Alardo JP, Razgallah B, et al. Seizure induced by ropivacaine. Ann Pharmacother 2001 Mar; 35(3): 311–3PubMedCrossRefGoogle Scholar
Breslin DS, Martin G, Macleod DB, et al. Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: a report of two cases. Reg Anesth Pain Med 2003 Mar; 28(2): 144–7PubMedGoogle Scholar
Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg 2003 Apr; 96(4): 1188–90PubMedCrossRefGoogle Scholar
Dernedde M, Furlan D, Verbesselt R, et al. Grand mal convulsion after an accidental intravenous injection of ropivacaine. Anesth Analg 2004 Feb; 98(2): 521–3PubMedCrossRefGoogle Scholar
Mullanu C, Gaillat F, Scemama F, et al. Acute toxicity of local anesthetic ropivacaine and mepivacaine during a combined lumbar plexus and sciatic block for hip surgery. Acta Anaesthesiol Belg 2002; 53(3): 221–3PubMedGoogle Scholar
Graf BM. The cardiotoxicity of local anesthetics: the place of ropivacaine. Curr Top Med Chem 2001 Aug; 1(3): 207–14PubMedCrossRefGoogle Scholar
Foxall G, McCahon R, Lamb J, et al. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia 2007 May; 62(5): 516–8PubMedCrossRefGoogle Scholar
Faccenda KA, Finucane BT. Complications of regional anaesthesia incidence and prevention. Drug Saf 2001; 24(6): 413–42PubMedCrossRefGoogle Scholar
Local anesthetics. In: Aronson JK, editor. Meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions. Amsterdam: Elsevier, 2006: 2116–57Google Scholar
Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356(9237): 1255–9PubMedCrossRefGoogle Scholar
Begaud B, Evreux JC, Jouglard J, et al. Unexpected or toxic drug reaction assessment (imputation): actualization of the method used in France. Therapie 1985; 40: 111–8PubMedGoogle Scholar
International Conference on Harmonisation: guidance on addendum to E2C clinical safety data management. Periodic safety update reports for marketed drugs; availability. Notice. Fed Regist 2004 Feb; 69(24): 5551–2Google Scholar
Weber JCP. Epidemiology of adverse reactions to non-steroidal antiinflammatory drugs. In: Rainsford KD, Velo GP, editors. Advances in inflammatory research. New York: Raven Press, 1984: 1–7Google Scholar
French Society of Regional Anesthesia and Intensive Care. Peripheral nerve block of limbs in the adult. Ann Fr Anesth Reanim 2003 Jun; 22(6): 567–81CrossRefGoogle Scholar
Thiessard F, Roux E, Miremont-Salame G, et al. Trends in spontaneous adverse drug reaction reports to the French pharmacovigilance system (1986–2001). Drug Saf 2005; 28(8): 731–40PubMedCrossRefGoogle Scholar
Hoppe J, Popham P. Complete failure of spinal anaesthesia in obstetrics. Int J Obstet Anesth 2007 Jul; 16(3): 250–5PubMedCrossRefGoogle Scholar
Hebl JR, Kopp SL, Schroeder DR, et al. Neurologic complications after neuraxial anesthesia or analgesia in patients with preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy. Anesth Analg 2006 Nov; 103(5): 1294–9PubMedCrossRefGoogle Scholar
Lacassie HJ, Muir HA, Millar S, et al. Perioperative anesthetic management for Cesarean section of a parturient with gestational diabetes insipidus. Can J Anaesth 2005 Aug; 52(7): 733–6PubMedCrossRefGoogle Scholar
Kelly D, Gudin JA, Brull SJ. Subcutaneous cysts: another cause of “failed” spinal anesthesia? J Clin Anesth 1996 Nov; 8(7): 603–4PubMedCrossRefGoogle Scholar
Carpenter RL, Hogan QH, Liu SS, et al. Lumbosacral cerebrospinal fluid volume is the primary determinant of sensory block extent and duration during spinal anesthesia. Anesthesiology 1998 Jul; 89(1): 24–9PubMedCrossRefGoogle Scholar
Munhall RJ, Sukhani R, Winnie AP. Incidence and etiology of failed spinal anesthetics in a university hospital: a prospective study. Anesth Analg 1988 Sep; 67(9): 843–8PubMedCrossRefGoogle Scholar
Brown DL, Ransom DM, Hall JA, et al. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg 1995 Aug; 81(2): 321–8PubMedGoogle Scholar
Berman RS, Eisele JH. Bacteremia, spinal anesthesia, and development of meningitis. Anesthesiology 1978 May; 48(5): 376–7PubMedCrossRefGoogle Scholar
Begaud B, Martin K, Haramburu F, et al. Rates of spontaneous reporting of adverse drug reactions in France [letter]. JAMA 2002 Oct; 288(13): 1588PubMedCrossRefGoogle Scholar
Belton KJ. Attitude survey of adverse drug-reaction reporting by health care professionals across the European Union: the European Pharmacovigilance Research Group. Eur J Clin Pharmacol 1997; 52(6): 423–7PubMedCrossRefGoogle Scholar
Pierfitte C, Begaud B, Lagnaoui R, et al. Is reporting rate a good predictor of risks associated with drugs? Br J Clin Pharmacol 1999 Mar; 47(3): 329–31PubMedCrossRefGoogle Scholar