Lidocaine, safety

Meta-analysis is a method often used to determine the effectiveness of a drug but to date it has rarely been used to assess safety. One case illustrates how this technique can help. Six studies examining the use of intravenous lidocaine for acute myocardial infarction did not, on an individual basis, give strong enough evidence to support the hypothesis that this technique could cause excess mortality. The meta-analysis, however, was able to demonstrate this. ... 

The safety of articaine has been studied in a series of three randomized trials (2). The adverse effects deemed to be related to articaine were headache, paresthesia/ hyperesthesia after injection, infection, and rash. There was one case of mouth ulceration. The overall incidence of adverse effects was comparable to that of lidocaine. 

The pharmacokinetics and safety of the 5% lidocaine patches have been studied in 20 healthy volunteers, who applied four patches to the skin either every 24 hours or every 12 hours for 3 days (67). Mean steady-state plasma concentrations were 186 and 225 ng/ml respectively, well below those required for an antidysrhythmic effect (1500 ng/ml) or a risk of toxicity (5000 ng/ml). The patches were well tolerated, with no major cutaneous adverse effects. This is in line with data from postmarketing surveillance studies, which have shown that since the availability of lidocaine patches in 1999, no adverse cardiac or other serious adverse events have been reported (68). 

The cardiovascular system is more resistant to the toxic effects of local anesthetics than the nervous system. Mild circulatory depression can precede nervous system toxicity, but seizures are more likely to occur before circulatory collapse. The intravenous dose of lidocaine required to produce cardiovascular coUapse is seven times that which causes seizures. The safety margin for racemic bupivacaine is much lower. The stereospecific levorotatory isomers levobupivacaine and ropivacaine are less cardiotoxic, and have a higher safety margin than bupivacaine, but not lidocaine in the case of ropivacaine this may be at the expense of reduced anesthetic potency (14,15). Toxicity from anesthetic combinations is additive. 

Lidocaine gel 2% has been compared with 0.5% tetracaine drops for topical anesthesia in cataract surgery in 25 patients (331). There were no corneal epithehal or ocular surface complications, demonstrating the safety of the gel, which may provide a more practical and efficient method of anesthesia, because it needs to be applied only once as opposed to three applications of the drops. 

The endothelial toxicity of local anesthetics has been assessed in pigs, as this might be relevant to the safety of agents given by intracameral injection (335). Lidocaine, mepivacaine, and prilocaine were safe, while bupivacaine in clinically effective concentrations resulted in significant cell reduction. 

Masket S, Gokmen F. Efficacy and safety of intracameral lidocaine as a supplement to topical anesthesia. J Cataract Refract Surg 1998 24(7) 956-60. 

Choosing the right LA agent is also a safety factor, and we will see below why simple lidocaine without adrenaline is the best choice of molecule for a phenol peel, both local and full-face. 

Layton D, Pearce G, Shakir S. Safety profile of tolterodine as used in general practice in England results of prescription event monitoring 2001. Drug Safety 2001 24 703-13. Hine LK, Laird N, Hewitt P, Chalmers TC. Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Arch Intern Med 1989 149 ... 

Seay RE. Comment bioavailability and safety of two ceftriaxone formulations - exposure to lidocaine questioned. Ann Pharmacother 1997 31 501-502. 

Shih RD, Hollander JE, Buistein JL, Nelson LS, Hoftinan RS, ( ck AM. CUnical safety of lidocaine in patients with cocaine-associated myocardial infarction. Arm Emerg Med (1 5)... 

Viscusi ER, Manvelian G. A randomized controlled study of the serum pharmacokinetics, effectiveness, and safety of thoracic extended-release epidural morphine (Depodur ) after lidocaine-epmephrme test dose administration in patients tmdergoing upper abdominal surgery. Int JPharmacol Ther 2009 47 659-670. 

Taddio A, Stevens B Craig K, Rastogi, P, Ben-David S, Shennan A, Mulligan P, Keren G. Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision. N JMed 1997 336 1197-1201. 

Efficacy and safety of 5% lidocaine medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy. Clin DrugInvestig2009 29 2 il-241. 

Nickel, J. C., et al. (2012). Continuous intravesical lidocaine treatment for interstitial cystitis/ bladder pain syndrome safety and efficacy of a new drug dehvery device. Science Translational Medicine, 4(143), 143ral00. 

A prospective randomised double-blind controlled trial comparing lidocaine and chloroprocaine for outpatient transurethral prostatectomy yielded similar clinical end points (primary end point duration of spinal block) [36 ]. Four patients in the lidocaine group developed TNS and one patient in the chloroprocaine group developed an acute cauda equina syndrome, which fully recovered after several weeks. Based on this, the authors conclude that they cannot recommend lidocaine in view of the high incidence of TNS and recommend close follow-up for chloroprocaine to ensure its safety profile. 

In many cases, no sedation is required except that provided by sterile Xylocaine (lidocaine) jelly that lubricates the catheter in boys. A quick examination performed by an experienced radiologist should not be painful. Postprocedural minor discomfort can occur, and it seems less worrisome when announced. Improvement by hydration and local care is the rule. In some children, major anxiety can be present. Inhalation of an equimolecular mixture of nitrous oxide and oxygen (Entonox) in fasting children can be helpful (Schmit and Sfez 1997). In uncooperative children who are too young to breathe gas, rectal midazolam can occasionally be used (Hypnovel 0.3 mg/kg, maximal dose 5 mg). For safety, sedation procedures should preferably be organized in collaboration with the department of anesthesiology. 

The numbers of daily injections of lidocaine for routine dentistry are enormous and added to the other uses of this and related compounds in medicine, then the safety of these drugs in emphasised. However, toxicity can occur and accidents such as self-injection with the drug during veterinary use are clearly... 

Prilocaine was synthesised in 1960 and was found to be very similar to lidocaine. It has a wider safety margin which is probably because it has a lower partition coefficient (Table 15.1) than lidocaine and also the amide bond is more readily enzymatically hydrolysed than that in lidocaine. It does have an additional problem in that the 2-methyl aniline hydrolysis product of metabolism (Fig. 15.10) can cause methaemoglobinaemia, a condition where the oxygen-carrying capacity of blood cells is reduced due to oxidation of iron (II) in haemoglobin to iron (III). Prilocaine has a chiral centre but it is administered as racemate. However, it is only one of the enantiomers which are rapidly hydrolysed in the liver causing toxicity this provides an example of how chirality can influence therapeutic activity. 

---