Good Practice in Postoperative and Procedural Pain Management ...

0.0625–0.75% (0.625–7.5 mg ml )1 ). In recommendeddoses, bupivacaine produces complete sensory blockade,and the extent of motor blockade depends onconcentration. Solutions of 0.0625% or 0.125% areassociated with a very low incidence of motor block, a0.25% solution generally produces incomplete motorblock, a 0.5% solution will usually produce moreextensive motor block, and complete motor block andmuscle relaxation can be achieved with a 0.75% solution.Hyperbaric solutions of 0.5% bupivacaine maybe used for spinal intrathecal block.Levobupivacaine is the S-enantiomer of bupivacaine,and it is equipotent but toxicity is slightly less. It isavailable in the same concentrations as bupivacaineand is used for similar indications; like bupivacaine, itis contraindicated for use in intravenous regional anesthesia(Bier’s block).Ropivacaine is an amide LA with an onset and durationof sensory block that is generally similar to thatobtained with bupivacaine but motor block may beslower in onset, shorter in duration, and less intense. Itis available in solutions of 0.2%, 0.75%, and 1%.(ii) Dosage, side effects, and toxicityThe dosage of bupivacaine, levobupivacaine, and ropivacainedepends on the site of injection, the procedure,and the status of the patient: suggested maxima aregiven in Table 6.2.1. A test dose may help to detectinadvertent intravascular injection, and doses shouldbe given in small increments. Slow accumulationoccurs with repeat administration and continuous infusions,especially in neonates.Table 6.2.1 Suggested maximum dosages of bupivacaine, levobupivacaine,and ropivacaineSingle bolus injection Maximum dosage (mgÆkg )1 )Neonates 2Children 2.5Continuous infusion(postoperative use)Neonates 0.2Children 0.4Maximum infusion rate (mgÆkg )1 Æh )1 )Bupivacaine is 95% bound to plasma proteins witha half-life of 1.5–5.5 h in adults and 8 h in neonates. Itis metabolized in the liver and is excreted in the urinemainly as metabolites with only 5–6% as unchangeddrug. Bupivacaine is distributed into breast milk insmall quantities. It crosses the placenta but the ratio offetal concentrations to maternal concentrations is relativelylow. Bupivacaine also diffuses into the CSF.The toxic threshold for bupivacaine is in the plasmaconcentration range of 2–4 mgÆml )1 . The two majorbinding proteins for bupivacaine in the blood are a1-acid glycoprotein, the influence of which is predominantat low concentrations, and albumin, which playsthe major role at high concentrations. Reduction inpH from 7.4 to 7.0 decreases the affinity of the a1-acidglycoprotein for bupivacaine but has no effect on albuminaffinity. For epidural infusion techniques in neonates,the reduced hepatic clearance of amide localanesthetics is the more important factor causing accumulationof bupivacaine than reduced protein bindingcapacity, particularly as protein levels tend to increasein response to surgery.Bupivacaine is more cardio toxic than other amidelocal anesthetics and there is an increased risk of myocardialdepression in overdose and when bupivacaineand antiarrhythmics are given together. Propranololreduces the clearance of bupivacaine. Levobupivacaineis slightly less cardio toxic and therefore safer butmaximum recommended doses are similar to those ofbuivacaine.Ropivacaine is about 94% bound to plasma proteins.The terminal elimination half-life is around 1.8 h, andit is extensively metabolized in the liver by the cytochromeP450 isoenzyme CYP1A2. Prolonged use ofropivacaine should be avoided in patients treated withpotent CYP1A2 inhibitors, such as the selective serotoninreuptake inhibitor (SSRI) fluvoxamine. Plasmaconcentrations of ropivacaine may be reduced byenzyme-inducing drugs such as rifampicin. Metabolitesare excreted mainly in the urine; about 1% of a doseis excreted as unchanged drug. Some metabolites alsohave a local anesthetic effect but less than that of ropivacaine.Ropivacaine crosses the placenta.6.2.2 Lidocaine, prilocaine, and EMLA(i) PreparationsLidocaine is an amide LA, which is used for infiltrationanesthesia and regional nerve blocks. It has a rapidonset of action and anesthesia is obtained within a fewminutes; it has an intermediate duration of action. Theaddition of a vasoconstrictor reduces systemic absorptionand increases both the speed of onset and theduration of action. Lidocaine is a useful surface anestheticbut it may be rapidly and extensively absorbedfollowing topical application to mucous membranes,and systemic effects may occur. Hyaluronidase mayª 2012 Blackwell Publishing Ltd, Pediatric Anesthesia, 22 (Suppl. 1), 1–79 67