It is mostly done with the patient asleep.

  The dose is far less than for adults (calculate in mg/kg).

  Look for changes in ECG rather than physiologic parameters to test dose.

  Always get patient consent if the child is older.

  Reported complications with regional anesthesia are far fewer in children than in adults.

Pharmacology of Local Anesthetics in Pediatric Patients

The two main classes oflocal anesthetics used in infants and children include the amino-amides (amides) and the aminoesters (esters). The amino-amides undergo enzymatic degradation by the liver, whereas the esters are hydrolyzed by plasma cholinesterases. These actions may play a very important role, particularly in neonates and infants.

Amides

These are the most commonly used local anesthetic solution in infants and children. The local anesthetics belonging to this class include lidocaine, bupivacaine, ropivacaine, and levobupivacaine. The choice of local anesthetic solution is based on the desired duration of local anesthetic action and the toxic effects of the local anesthetic solution that is used. Unlike in adult patients, neonates are not able to oxidize and reduce amide local anesthetic agents and hence differ vastly in their ability to reduce toxicity related to local anesthetics.^{10, 11} The conjugation oflocal anesthetics in the liver reaches peak adult levels at approximately 3 months of age.^{12, 13} Some local anesthetics can have higher blood concentrations in adolescents than in adults owing to increased vascular absorption¹⁴; hence, caution must be exercised in older children. Peak plasma concentrations are obtained in children in about 30 minutes after caudal blockade.¹⁵ Although clearance is similar in older children and adolescents, the steady- state volume of distribution (Vdss is increased in children compared with that in adults.¹⁶ All amide local anesthetics have been shown to have diminished clearance in neonates and infants younger than 3 months of age, with steady maturation until they reach adult clearance at about 8 months of age.¹⁷ The risk of toxicity associated with repeated doses of local anesthetics is greater in children than in adults.¹⁸ Amino-esters may have a rapid clearance in neonates.¹⁹

        DOSING OF LOCAL ANESTHETICS IN PEDIATRIC PATIENTS

Most pediatric drug doses are based on the weight of the patient⁶⁰ (Table 54-1). However, this may not be applicable to local anesthetic solution. Studies done on infants undergoing spinal anesthesia demonstrated a larger requirement of local anesthetic solution (weight-scaled) compared with their adult counterparts using bupivacaine or tetracaine.²⁰ However, studies on rat sciatic nerve models demonstrated similar trends in the neonatal, adolescent, and adult rat.²¹

Table 54-1.

Maximum Recommended Doses and Approximate Duration of Action of Commonly Used Local Anesthetic Agents

Tachyphylaxis

Tachyphylaxis is a clinical phenomenon whereby repeated dosing of local anesthetics leads to decreasing effects. There seems to be a correlation between dosing intervals and the presence of pain; dosing intervals that are short enough to avoid breakthrough pain result in a lesser chance of tachyphylaxis.

Toxicity of Local Anesthetic Solutions

Toxicity of local anesthetics solutions includes cardiac, peripheral vascular, neurologic, and allergic reactions⁶⁰ (Table 54-2). Dose is always calculated in children on a milligram per kilogram basis rather than predicted volumes as in adult regional anesthesia. Children given local anesthetic solutions, particularly when used as continuous infusions, should be monitored continuously for adverse effects. Toxicity oflocal anesthetics in children include cardiovascular^22–24 and central nervous system toxicity²⁵ and allergic reactions to ester local anesthetic solutions. The risk of severe toxicity can be decreased by limiting the local anesthetic dosage in children²⁶ (see Table 54-2).

        SPECIFICS OF LOCAL ANESTHETICS IN PEDIATRIC REGIONAL ANESTHESIA

Bupivacaine

Bupivacaine is the most commonly used local anesthetic solution in infants and children in North America. The pharmacokinetics and pharmacodynamics of bupivacaine have been well documented in the literature.²⁷·²⁸ It is imperative for the surgeon to consider using a supplemental local anesthetic solution because the infiltration anesthesia adds to the total dosage oflocal anesthetic solution in the systemic circulation. The preferred concentration for children is 0.25-0.5% for peripheral nerve blocks and 0.1% for continuous infusions. Older children can tolerate a higher dose of local anesthetic solution (0.4 mg/kg/h) compared with neonates and infants (0.2 mg/kg/h).¹⁸

        Metabolism: Bupivacaine is well bound to oc-1 glycoprotein. Because of low levels of albumin and cc-1 glycoprotein in neonates, the free fraction of bupivacaine may be greater, thereby leading to a greater risk of toxicity.²⁹ Bupivacaine is an isomer with both l- and D-enantiomer, the D-enantiomer causing most of the adverse effects that are seen in humans. The incidence of cardiac toxicity is greater than neurotoxicity in children. This is due to the concomitant use of general anesthesia, which masks the neurotoxicity; hence, cardiac toxicity is first seen with overdosing oflocal anesthetic or intravascular placement.

        Dosage: The dosage of bupivacaine is limited to 2-4 mg/kg for a single-dose injection and 0.2-0.4 mg/kg for a continuous infusion. It is always judicious to use intermittent and slow bolus injections of bupivacaine to detect intravascular injection. A test dose with epinephrine-containing solution is often used. This facilitates detection of intravascular placement. Besides the use of the usual cardiovascular signs including increase in heart rate and blood pressure, the increasing amplitude of T waves is suggestive of intravascular placement.³⁰ This is particularly useful in infants whose baseline heart rate may be higher and in whom subtle increases to heart rate may go undetected.

Ropivacaine

Ropivacaine is a newer amide local anesthetic that is being used more frequently in pediatric surgery. It is an l- enantiomer with fewer cardiovascular and central nervous system side effects compared with bupivacaine. The lethal dose of ropivacaine in rats is higher than bupivacaine.³¹ Ropivacaine in an equipotent dose may offer less of a motor block compared with that of bupivacaine.³² Pediatric trials have demonstrated a longer duration of action with ropivacaine than with mepivacaine when used for peripheral nerve blockade.³³ Caution should be exercised while using ropivacaine in children as well, because cases of cardiovascular toxicity have been reported.³⁴

        Pharmacokinetics: Pharmacokinetic data are available in children on the use of ropivacaine in continuous infusions as well as for single-shot injections.^35–, Although ropivacaine is safer in children owing to its L-enantiomer structure, caution must be exercised because complications from intravascular injections have been reported. aj-Acid glycoprotein is an acute-phase reactant that increases in the phase of injury such as surgery. In neonates and infants, this response is not surmountable because of the decreased amount of oc i -acid glycoprotein. This facilitates the metabolism oflocal anesthetic solution. As a result, the free fraction of the local anesthetic is increased in the plasma,³⁹ which contributes to the greater toxicity of local anesthetics in infants and neonates compared with that in older children and adults.

Levobupivacaine

Levobupivacaine is a newer L-enantiomer with fewer adverse effects than bupivacaine. Pharmacokinetic data are available in children, and the dosage interval is not very different from that of bupivacaine.^40–43 The prevalent use oflevobupivacaine is not seen in children owing to nonavailability of the drug in the United States.

        Toxicity: Levobupivacaine has been shown to be less toxic in the animal model compared with bupivacaine.⁴⁴ Although this drug provides the practitioner with an option to use a drug that is less cardiotoxic, caution should be exercised in use of this drug and adequate care should be taken to avoid intravascular injection. Animal experiments have shown that levobupivacaine has less myocardial depression and a decreased incidence of inducing fatal dysrhythmias compared with bupivacaine.

        ESTER-TYPE LOCAL ANESTHETICS

Ester local anesthetics differ from amide local anesthetics in that they are metabolized by plasma cholinesterases.^45–47 As a result, metabolism of ester local anesthetics depends on plasma cholinesterase levels.^48–51 Hence in populations with decreased plasma cholinesterase levels, such as neonates and infants, the plasma level of these drugs may be increased and lead to potentially toxic drug levels. The presence of plasma cholinesterase also limits the duration of activity of these drugs, leading to a shortened activity. The most common ester local anesthetics used in infants and children are chloroprocaine and tetracaine. These drugs, however, are not commonly used in children except as an adjuvant to spinal anesthesia in formerly premature infants undergoing spinal anesthesia or as the sole anesthetic solution for caudal analgesia.⁵² Tetracaine is used for spinal anesthesia, especially in premature infants, as the sole anesthetic for inguinal hernia repair.⁵³ 2-Chloroprocaine has been used extensively in children for analgesia in the central neuraxial space.⁵⁴

        TOPICAL ANESTHESIA

It is important to discuss the use of topical anesthesia in children because it is commonly used in clinical practice to provide analgesia for intravenous catheter placements, lumbar punctures, and other invasive procedures in children. The most common preparations include lidocaine, tetracaine, benzocaine, and prilocaine. The topical anesthetic solution permeates through the skin to provide analgesia. The two most common preparations that are available include EMLA (Eutectic Mixture of Local and Anesthetics) and LMX-4, a 4% liposomal lidocaine solution used as a topical anesthetic. Both drugs have undergone extensive trials and have been used in children for repeated painful procedures.^55–58 The introduction of other modalities for pain control including iontophoretic local anesthetic drug delivery can be used for pain control in simple procedures including intravenous catheter placements.⁵⁹

        SUMMARY

In summary, regional anesthesia in infants and children has been a well-established entity, although it remains vastly underutilized. Adequate education of the anesthesiology trainees on the use of regional anesthesia, its advantages, and its side effects are of paramount importance for its successful and safe application in the pediatric population.

References

1.  Bainbridge W: Analgesia in children by spinal injection with a report of a new method of sterilization of the injection fluid. Med Rec 1900;58:937-940.

2.  Campbell MF: Caudal analgesia in children and infants. J Urol 1933;30:245.

3.  Anand KJ, Sippell WG, Aynsley-Green A: Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: Effects on the stress response. Lancet 1987;1:62-66.

4.  Taddio A, Katz J, Ilersich AL, Koren G: Effect of neonatal circumcision on pain response during subsequent routine vaccination [see comments]. Lancet 1997;349:599-503.

5.  Marhofer P, Sitzwohl C, Greher M, Kapral S: Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children. Anaesthesia 2004;59:642-646.

6.  Suresh S, Wheeler M: Practical pediatric regional anesthesia. Anesthesiol Clin North Am 2002;20:83-113.

7.  Tait AR, Voepel-Lewis T, Malviya S: Do they understand? (Part II): Assent of children participating in clinical anesthesia and surgery research. Anesthesiology 2003;98:609-614.

8.  Krane EJ, Dalens BJ, Murat I, Murrell D: The safety of epidurals placed during general anesthesia. Reg Anesth Pain Med 1998;23:433- 438.

9.  Giaufre E, Dalens B, Gombert A: Epidemiology and morbidity of regional anesthesia in children: A one-year prospective survey of the French-Language Society of Pediatric Anesthesiologists. Anesth Analg 1996;83:904-912.

10.  Besunder IB, Reed MD, Blumer IL: Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic- pharmacodynamic interface (Part I). Clin Pharmacokinet 1988; 14: 189-216.

11.  Besunder IB, Reed MD, Blumer JL: Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic- pharmacodynamic interface (Part II). Clin Pharmacokinet 1988; 14: 261-286.

12.  Rane A, Sjoqvist F: Drug metabolism in the human fetus and newborn infant. Pediatr Clin North Am 1972;19:37-49.

13.  Levy G: Pharmacokinetics of fetal and neonatal exposure to drugs. Obstet Gynecol 1981;58:9S-16S.

14.  Rothstein P, Arthur GR, Feldman HS, et al: Bupivacaine for intercostal nerve blocks in children: Blood concentrations and pharmacokinetics. Anesth Analg 1986;65:625-632.

15.  Ecoffey C, Desparmet J, Maury M, et al: Bupivacaine in children: Pharmacokinetics following caudal anesthesia. Anesthesiology 1985;63:447-448.

16.  Murat I, Montay G, Delleur MM, et al: Bupivacaine pharmacokinetics during epidural anaesthesia in children. Eur I Anaesthesiol 1988;5:113-120.

17.  Mazoit JX, Denson DD, Samii K: Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 1988;68:387- 391.

18.  Berde CB: Toxicity oflocal anesthetics in infants and children. [Review], J Pediatr 1993;122(Pt 2):S14?S20.

19.  Flenderson K, Sethna NF, Berde CB: Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J Clin Anesth 1993;5:129-133.

20.  Frumiento C, Abajian JC, Vane DW: Spinal anesthesia for preterm infants undergoing inguinal hernia repair. Arch Surg 2000; 135:445451.

21.  Kohane DS, Sankar WN, Shubina M, et al: Sciatic nerve blockade in infant, adolescent, and adult rats: A comparison of ropivacaine with bupivacaine. Anesthesiology 1998;89:1199-1208.

22.  Kasten GW, Martin ST: Bupivacaine cardiovascular toxicity: Comparison of treatment with bretylium and lidocaine. Anesth Analg 1985;64:911-916.

23.  Murat I, Esteve C, Montay G, et al: Pharmacokinetics and cardiovascular effects of bupivacaine during epidural anesthesia in children with Duchenne muscular dystrophy. Anesthesiology 1987;67:249- 252.

24.  Graf BM: The cardiotoxicity of local anesthetics: The place of ropivacaine. Curr Top Med Chem 2001;1:207-214.

25.  Bergman BD, Hebl JR, Kent I, Horlocker TT: Neurologic complications of405 consecutive continuous axillary catheters (table). Anesth Analg 2003;96:247-252.

26.  Berde CB: Convulsions associated with pediatric regional anesthesia [editorial comment] [see comments], Anesth Analg 1992;75:164- 166.

27.  Ecoffey C, Desparmet I, Maury M, et al: Bupivacaine in children: Pharmacokinetics following caudal anesthesia. Anesthesiology 1985;63:447-448.

28.  Murat I, Montay G, Delleur MM, et al: Bupivacaine pharmacokinetics during epidural anaesthesia in children. Eur J Anaesthesiol 1988;5(2):113-120.

29.  Ecoffey C, Desparmet J, Maury M, et al: Bupivacaine in children: Pharmacokinetics following caudal anesthesia. Anesthesiology 1985;63:447-448.

30.  Freid EB BAVR: Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of bupivacaine with epinephrine in infants. Anesthesiology 1993;79:394-398.

31.  Dony P, Dewinde V, Vanderick B, et al: The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats. Anesth Analg 2000;91:1489-1492.

32.  Da Conceicao MJ, Coelho L: Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric patients. Br I Anaesth 1998;80:507-508.

33.  Fernandez-Guisasola 1, Andueza A, Burgos E, et al: A comparison of 0.5% ropivacaine and 1% mepivacaine for sciatic nerve block in the popliteal fossa. Acta Anaesthesiol Scand 2001;45:967-970.

34.  Petitjeans F, Mion G, Puidupin M, et al: Tachycardia and convulsions induced by accidental intravascular ropivacaine injection during sciatic block. Acta Anaesthesiol Scand 2002;46:616-617.

35.  Ivani G, Mereto N, Lampugnani E, et al: Ropivacaine in paediatric surgery: Preliminary results. Paediatr Anaesth 1998;8:127-129.

36.  Ivani G, Mazzarello G, Lampugnani E, et al: Ropivacaine for central blocks in children. Anaesthesia 1998;53:Suppl 6.

37.  Ala-Kokko Tl, Partanen A, Karinen J, et al: Pharmacokinetics of 0.2% ropivacaine and 0.2% bupivacaine following caudal blocks in children. Acta Anaesthesiol Scand 2000;44:1099-1102.

38.  Dalens B, Ecoffey C, Joly A, et al: Pharmacokinetics and analgesic effect of ropivacaine following ilioinguinal/iliohypogastric nerve block in children. Paediatr Anaesth 2001;11:415-420.

39.  Mazoit JX, Dalens BJ: Pharmacokinetics oflocal anaesthetics in infants and children. Clin Pharmacokinet 2004;43:17-32.

40.  Ivani G, De Negri P, Lonnqvist PA, et al: A comparison of three different concentrations of levobupivacaine for caudal block in children (table). Anesth Analg 2003;97:368-371.

41.  Lerman J, Nolan J, Eyres R, et al: Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: A multicenter trial. Anesthesiology 2003;99:1166-1174.

42.  Ala-Kokko TI, Raiha E, Karinen J, et al: Pharmacokinetics of 0.5% levobupivacaine following ilioinguinal-iliohypogastric nerve blockade in children. Acta Anaesthesiol Scand 2005;49:397-400.

43.  Foster RH, Markham A: Levobupivacaine: A review of its pharmacology and use as a local anaesthetic. Drugs 2000;59:551-579.

44.  Mather LE, Huang YF, Veering B, Pryor ME: Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep. Anesth Analg 1998;86:805-811.

45.  Tobias JD, O–Dell N: Chloroprocaine for epidural anesthesia in infants and children. AANA J 1995;63:131-135.

46.  Raj PP, Ohlweiler D, Hitt BA, Denson DD: Kinetics of local anesthetic esters and the effects of adjuvant drugs on 2-chloroprocaine hydrolysis. Anesthesiology 1980;53:307-314.

47.  Tobias JD, Rasmussen GE, Holcomb GW III, et al: Continuous caudal anaesthesia with chloroprocaine as an adjunct to general anaesthesia in neonates. Can J Anaesth 1996;43(l):69-72; 69-72.

48.  Crowhust JA: Cholinesterase deficiency. Anaesth Intensive Care 1983;11:7-9.

49.  Kuhnert BR, Philipson EH, Pimentai R, Kuhnert PM: A prolonged chloroprocaine epidural block in a postpartum patient with abnormal pseudocholinesterase. Anesthesiology 1982;56:477—478.

50.  Monedero P, Hess P: High epidural block with chloroprocaine in a parturient with low pseudocholinesterase activity. Can I Anaesth 2001;48:318-319.

51.  Kuhnert BR, Kuhnert PM, Prochaska AL, Gross TL: Plasma levels of 2-chloroprocaine in obstetric patients and their neonates after epidural anesthesia. Anesthesiology 1980;53: 21-25.

52.  Henderson K, Sethna NF, Berde CB: Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J Clin Anesth 1993;5:129-133.

53.  Krane EJ, Haberkern CM, Jacobson LE: Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: Prospective comparison of spinal and general anesthesia. Anesth Analg 1995;80:7-13.

54.  Henderson K, Sethna NF, Berde CB: Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J Clin Anesth 1993;5:129-133.

55.  Acharya AB, Bustani PC, Phillips JD, et al: Randomised controlled trial of eutectic mixture of local anaesthetics cream for venipuncture in healthy preterm infants. Arch Dis Child Fetal Neonatal Ed 1998;78:F138-F142.

56.  Benini F, Johnston CC, Faucher D, Aranda JV: Topical anesthesia during circumcision in newborn infants. JAMA 1993;270:850-853.

57.  Courrier E, Karoubi P, el Hanache A, et al: Use of EMLA cream in a department of neonatology. Pain 1996;68:431-434.

58.  Eichenfield LF, Funk A, Fallon-Friedlander S, Cunningham BB: A clinical study to evaluate the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics cream for pain reduction of venipuncture in children. Pediatrics 2002;109:1093-1099.

59.  Sethna NF, Verghese ST, Hannallah RS, Solodiuk JC, Zurakowski D, Berde CB: A randomized controlled trial to evaluate S-Caine patch for reducing pain associated with vascular access in children. Anesthesiology 2005;102:403-408.

60.  Suresh S, Cote CJ: Local anesthetics for infants and children. In: Yaffe SJ, Aranda JV (editors): Neonatal and Pediatric Pharmacology, Therapeutic Principles in Practice, 3rd ed. Lippincott Williams & Wilkins, 2004, pp. 663-668.

B. Pediatrie Epidural & Caudal Analgesia & AnesthesiaThe History of Local Anesthesia

Ban C.H.Tsui, MD

• Michael Fredrickson, MD

• Santhanam Suresh, MD

        EPIDURAL BLOCKADE TECHNIQUE FOR PEDIATRIC SURGERY (TECHNICAL)

Introduction

Epidural analgesia has many beneficial effects in the pediatric patient population. In clinical practice, it is commonly used to augment general anesthesia and to manage postoperative pain. Effective postoperative pain relief from epidural analgesia has numerous benefits including earlier ambulation, rapid weaning from ventilators, reduced time spent in a catabolic state and lowered circulating stress hormone levels.¹ Precise placement of epidural needles and catheters for single-shot and continuous epidural anesthesia ensures that the dermatomes involved in the surgical procedure are selectively blocked, allowing for lower doses of local anesthetics and sparing of unnecessary blockade in the regions where blockade is not desired.^2–4

Anatomic Considerations

Significant anatomic differences in children compared with adults should be considered in using regional anesthesia in children. For instance, in neonates and infants, the conus medullaris is located lower in the spinal column (at approximately the L3 vertebra) compared with that in adults, in whom it is situated at approximately the LI vertebra. This dissimilarity is a result of different rates of growth between the spinal cord and the bony vertebral column in infants. However, at approximately 1 year of age the conus medullaris reaches an LI level similar to that in an adult.

        The sacrum of children is also more narrow and flat compared with that in the adult population. At birth, the sacral plate, which is formed by five sacral vertebrae, is not completely ossified and continues to fuse until the child is approximately 8 years of age. The incomplete fusion of the sacral vertebral arch forms the sacral hiatus. The caudal epidural space can be accessed easily in infants and children through the sacral hiatus. Because of the continuous development of the sacral canal roof, there is considerable variation in the sacral hiatus. In children, the sacral hiatus is located more cephalad compared with that in adults. Therefore, caution is warranted when placing caudal blocks in infants because the dura may end more caudad and thereby increase the risk of accidental dural puncture.

        It has also been suggested that the epidural fat is less densely packed in children than in adults.⁵ This loosely packed epidural fat may not only facilitate the spread of local anes- thestic, but it may also allow the unimpeded advancement of epidural catheters from the caudal epidural space to the lumbar and thoracic levels.

Clinical Pearls

Considerations for Choosing Local Anesthetic Solutions for Epidural & Caudal Anesthesia & Analgesia

Newer local anesthetics with favorable potencies, durations of effect, and decreased toxicity profiles have been introduced in the past decade. Local anesthetic concentration and volume are important factors in determining the density and level of blockade. Because most pediatric patients receive epidural analgesia in conjunction with a general anesthetic, the main purpose of the epidural catheter is to deliver sufficient local anesthetic solution for effective intraoperative and postoperative analgesia. Knowledge of total drug dose is important to avoid local anesthetic toxicity, particularly in pediatric patients.

Clinical Pearls

        A more detailed description of local anesthetic solutions, their characteristics and toxic potential has been described in Chapters 6 and 7. As a general rule, however, high concentrations of local anesthetics such as 0.5% bupivacaine or 0.5% ropivacaine are seldom used in pediatric populations, particularly in the epidural space. Instead, larger volumes of more dilute local anesthetic are more commonly used to cover multiple dermatomes. Opioids prolong the duration of analgesia of local anesthetic, but have also been associated with unacceptable side effects, particularly in pediatric outpatients. Various nonopioid adjuncts such as clonidine and ???-agonists offer more favorable side-effect profiles; however, relatively little information is available regarding their use pediatric patients.

Selection of Epidural Local Anesthetic Solutions

Clinical Pearls

        Bupivacaine and ropivacaine are the two most commonly used local anesthetics for neuraxial anesthesia in children. Lidocaine is not often used because of its short duration of action and excessive motor block. Body weight is usually a better correlate than patient age in predicting spread of local anesthetic after a caudal block.⁶ The maximal safe dose of bupivacaine is 2.5-4 mg/kg.⁷ For caudal use, the optimum concentration of bupivacaine is 0.125-0.175%.⁹ Compared with the 0.25% preparation, this concentration provides a similar duration of postoperative analgesia (4-8 hours) but with less motor blockade.⁸ Some clinicians prefer administering doses on a volume-per-weight basis. A dose of 1.0 mL/kg of a dilute solution such as 0.125% bupivacaine to a maximum volume of 30 mL can reliably provide T10 sensory block without exceeding maximum levels recommended in the literature.⁹ Higher doses such as 1.25 mL/kg, or even 1.5 mL/kg, may be administered to provide a more cephalad block without the risk of local anesthetic toxicity.⁹ For continuous epidural infusion, a commonly accepted dosage guideline of bupivacaine is 0.2 mg/kg/h for neonates and 0.4 mg/kg/h for older children.¹⁰ Cumulative toxicity is a concern even at lower rates of local anesthetic solution infusions.³ The alternate use of 2-chloroprocaine may be well tolerated by neonates.¹¹

        Newer local anesthetic agents include the L-enantio- mers ropivacaine and levobupivacaine. Ropivacaine has a higher therapeutic index than the older local anesthetic bupivacaine.^121314–15 At low concentrations, ropivacaine may produce less motor block and comparable analgesia when compared with bupivacaine with a decreased incidence of cardiac and central nervous system toxicity.⁹ Because of its possible vasoconstricting properties, ropivacaine may undergo slower systemic absorption than bupivacaine.^16–17 This may have clinical implications when a prolonged local anesthetic infusion is used in children with impaired hepatic function.¹⁸ For a single-shot caudal block, a bolus of 1 mL/kg of 0.2% ropivacaine is recommended.^19,20 An infusion of 0.1% ropivacaine at 0.2 mg/kg/h in infants and 0.4 mg/kg/h in older children lasting no longer than 48 hours has also been shown to be effective and safe.²⁰

        Levobupivacaine, the S( —)-isomer of bupivacaine, is less likely to cause myocardial depression and fatal arrhythmias and is also less toxic to the central nervous system than racemic bupivacaine. A dose of 0.8 mL/kg of 0.25% levobupi- vacine injected caudally provides analgesia in children having penile or groin surgery.²¹ For continuous epidural infusions, the dose for levobupivacaine is similar to that for racemic bupivacaine.¹⁰

Adjuvants to Local Anesthetic Solutions

Adjuvants may be used to prolong the duration of blockade, particularly for single-shot caudal epidural blocks.²² Singleshot caudal block is used mainly for ambulatory surgery. The major problem associated with this technique is the limited duration of analgesia and unwanted motor blockade. Recent research has focused on trying to resolve these problems with the addition of various adjuvants.

Epinephrine

The most commonly used adjuvant for single-shot caudal anesthesia is epinephrine in a concentration of 1:200,000. Epinephrine has the added benefit of serving as a marker for an inadvertent intravascular injection.

Opioids

Epidural opioids may enhance and prolong analgesia. However, opioid use in an ambulatory setting may not be advisable because of the potential for respiratory depression and other unfavorable side effects (eg, nausea and vomiting, itching, urinary retention).⁷ As a result, the use of caudal epidural opioids in children should be restricted to special clinical situations.^2324–25 Fentanyl has been used with desirable effects for epidural analgesia in adults for a number of years. Whether there is benefit for fentanyl as an additive in children undergoing single-shot caudal blockade is still debated amongst clinicians.^26–27 One study found an increased incidence of nausea and vomiting when fentanyl was added to the local anesthetic solution for a single-shot caudal block.²‘ A dose of 2 mcg/kg of fentanyl for single-shot caudal anesthesia along with the standard local anesthetic solution has been recommended for more extensive or painful procedures or in patients who have a urinary catheter in the postoperative period. The addition of 1 mcg/mL to 2 mcg/mL of fentanyl to 0.1% bupivacaine for continuous epidural infusions has also been used with success in neonates and children in a well-monitored inpatient setting.²⁸

Clonidine

Clonidine, an oti -agonist, acts by stimulating descending noradrenergic medullospinal pathways; this inhibits the release of nociceptive neurotransmitters in the dorsal horn of the spinal cord. The addition of clonidine ( 1-5 mcg/kg) can improve the analgesic effect of local anesthetics for single-shot caudal blockade as well as prolong its duration of action without the unwanted side effects of epidural opioids.²⁹ For continuous epidural infusions, clonidine 0.1 mcg/kg/h has been used with good effect.³⁰ It should be cautioned that higher doses have been associated with sedation and hemodynamic instability in the form of hypotension and bradycardia, and doses as low as 2 mcg/kg have been associated with postoperative sedation.³¹ In addition, epidural clonidine blunts the ventilatory response to increasing levels of end-tidal carbon dioxide (PCO2). Although respiratory depression does not appear to be a common problem,³² apnea has been reported in a term neonate who received a caudal block consisting of 1 mL/kg of 0.2% ropivacaine with clonidine 2 mcg/kg.³³ Caution should be exercised while using clonidine in very young infants because of the sedation and hypotension that may ensue.

Ketamine

The addition of ketamine or 5-ketamine to single-shot caudal block prolongs the analgesic effect of local anesthetics. The main disadvantages of ketamine are its psychomimetic effects. However, at low doses (0.25-0.5 mg/kg), ketamine is effective without noticeable behavioral side effects.²⁹ Ketamine 1 mg/kg can also be used as an effective caudal analgesic solely without the addition of local anesthetic solution.³⁴·³⁵ The combination of S(+)-ketamine (0.5-1 mg/kg) and clonidine ( 1 or 2 mcg/kg) has been shown to provide effective analgesia after inguinal herniotomy in children with prolonged duration of effect (>20 hours) without any adverse CNS effects or motor impairment.^35,36 However, the safety of ketamine for central neuraxial block has been questioned, particularly with the racemic formulations that contain preservatives. Results from a small clinical trial and case series indicate that a singlebolus administration of preservative-free S-ketamine appears to be safe and effective.^7–10 Regardless, these reports lack statistical power and detailed postoperative evaluations to draw definitive conclusions regarding the safety of ketamine for neuraxial use. An additional concern regarding use of ketamine in neonates relates to a controversial series of animal studies suggesting that ketamine can produce apoptotic neurodegeneration in the developing brain.^37,38 Other infant animal studies have demonstrated that ketamine may have a neuroprotective effect.^39–40 Nevertheless, many anesthesiologists are hesitant to introduce caudal S-ketamine into their routine clinical practice, and ketamine is unlikely to be widely adopted in countries where preservative-free formulas are not available.

Midazolam

Epidural midazolam (50 mcg/kg), when used alone, produces postoperative analgesia without motor weakness or behavioral changes.²⁹ This is due to its ability to inhibit GABA receptors in the spinal cord. When added to local anesthetic solutions, midazolam can prolong the duration of analgesia, but this effect has not been consistently demonstrated.⁴¹ The safety of midazolam for neuraxial use, similar to that of ketamine has not been established, and a preservative-free formulation is not universally available/

Neostigmine

Neostigmine (2 mcg/kg) alone produces postoperative analgesia by inhibiting the breakdown of acetylcholine at muscarinic receptors in the dorsal horn.’ When combined with bupivacaine, a significant synergistic effect is observed. The addition of neostigmine (2 mcg/kg) to 0.25% bupivacaine prolongs the duration of analgesia from 5 to 20 hours after hypospadias repair.^1,42 However, it is associated with an unacceptably high incidence of vomiting (20-30%).⁴² This likely precludes its use particularly in an ambulatory setting. Preservative-free neostigmine has not been widely available and has limited applications in pediatric regional anesthesia.

Complications Associated with Epidural and Caudal Analgesia

Neurologic Injury

Major complications from either single-shot or continuous epidural blocks are rare if proper technique is used.^43,44 A large prospective study, which summarized data from over 15,000 central blocks in children, reported no incidence of permanent neurologic injuries and concluded that the incidence of complications is rare.⁴⁵ However, three infant deaths and two other incidences of paraplegia and quadriplegia were reported in another large retrospective report published in 1995 with over 24,000 epidural blocks in children.⁴⁶ This study also reported two cases of transient paresthesia.⁴⁶ Although the overall risk seems very low, devastating complications from direct damage to the spinal cord can occur during direct thoracic and high lumbar epidural needle placement. Because the placement of epidural needles/catheters is usually performed with the patient under sedation or general anesthesia, the fact that unconscious patients are unable to report pain or paresthesias (the currently accepted warning sign of needle encroachment on the spinal cord) raises concern.^474849–50 Recently, a case report described a spinal cord injury after placing single shot thoracic epidural under general anesthesia for appendectomy.⁵¹ This case report highlights the need for clinicians to routinely assess risk/benefit ratio of placing direct thoracic epidurals for less extensive surgery. Thoracic and high lumbar epidural catheter placement in particular should be limited to extensive thoracic and abdominal procedures and should be performed by anesthesiologists with experience in thoracic epidural placement. Before using a direct thoracic approach in patients younger than 2 years old, some prefer to make an attempt to thread the epidural catheter from the lumbar or caudal space with a proper epidural confirmation technique.

Epidural Hematoma

Epidural hematoma associated with epidural analgesia is extremely rare. This may be because anticoagulation protocols are rarely indicated during the perioperative period in pediatric patients. Nonetheless, epidural analgesia should be avoided in patients with clinically significant coagulopathy or thrombocytopenia. The guidelines for use of epidural anesthesia in anticoagulated adult patients should probably also be applied in pediatric patients.

Infection

Compared with lumbar epidural catheters, there is some concern regarding catheter infection with the prolonged use of caudally placed catheters owing to the proximity of the sacral hiatus to the rectum. Although studies have not found clinical evidence of higher infection rates with the caudal approach, bacterial colonization has been reported as higher. Staphylococcus epidermidis is the predominant microorganism colonized on the skin and catheters oflumbar and caudal epidurals.⁵² Gram-negative bacteria have also been demonstrated on the tips of the caudal catheter.⁵² Although the overall infection rate associated with caudal epidural catheters appears to be low, isolated case reports exist of infection related to epidural catheters in children. Even with widely used single-shot caudal blocks, infection such as sacral osteomyelitis can still occur.⁵³

        Perforation of the rectum may occur if the caudal needle is angled too steeply.⁵⁴ To reduce the risk of contamination by stool and urine, techniques such as catheter tunneling and fixing the catheter with occlusive dressing in a cephalad direction can be used.^28,55 A strict aseptic technique including the use of a sterile closed-infusion system should also be used, and care should be taken to avoid local tissue trauma. Daily inspection of the dressing and entry site are also important.

Dural Puncture and Postdural Headache

Dural puncture during caudal epidural analgesia is uncommon if caution is taken to avoid advancing the needle too far into the sacral canal. Treatment for postdural puncture headache (PDPH) includes bed rest, oral or intravenous hydration, simple analgesia such as regular acetaminophen, nonsteroidal antiinflammatory agents, and antiemetics. Bed rest, although relieving the severity of the headache, has no effect on the incidence or duration of PDPH. Hydration should be maintained to continue cerebrospinal fluid production and to avoid dehydration, which may alleviate symptoms. Simple analgesics may be all that is required until there is spontaneous resolution of symptoms.

        In adults, caffeine has been used for both prophylaxis and treatment for PDPH. Caffeine causes cerebral vasoconstriction by blocking adenosine receptors, which dilate vessels when activated. Reducing cerebral blood flow decreases the amount of blood in the brain and may lessen the traction on pain-sensitive intracranial structures, relieving PDPH.⁵⁶ Caffeine is not frequently used in children for relief of PDPH, and an optimal dose is not known. Side effects are usually mild and may include nausea, insomnia, restlessness, and lightheadedness.

        The use of epidural blood patch to treat PDPH has been used with success in adults since I960.⁵⁷ There are now many reports of its successful use in children as well.⁵⁷ An epidural blood patch is thought to be effective through the formation of a gelatinous cover over the dural hole by the injected blood. In the short term, the epidural blood patch seals the hole and relieves cerebrospinal fluid hypotension both by mass effect from cerebrospinal fluid cranial displacement and by increasing the intracranial volume and pressure.⁵⁸ Actual healing takes place over the longer term. In children, it is recommended that approximately 0.3 mL/kg is injected in the awake or mildly sedated patient, if possible, to detect the appearance of radicular symptoms.

Hemodynamic Effects and Total Spinal Anesthesia

Significant changes in blood pressure are uncommon in pediatric patients after the proper administration epidural analgesia. A high sympathetic single-shot caudal block to

T6 evoked no significant changes in heart rate, cardiac index, or blood pressure in children.^59,60 Even when thoracic epidural block is combined with general anesthesia, cardiovascular stability is usually maintained in otherwise healthy pediatric patients. Hypotension should prompt anesthesiologists to immediately rule out a total spinal and/or intravascular injection leading to local anesthetic toxicity. After these complications are ruled out, other causes such as hydration status, intravascular filling pressure, inotropic state, and the depth of anesthesia should be assessed. If a total spinal occurs, supportive measures must be provided until the effect of the block has dissipated. However, in the event of life-threatening extensions of total spinals and if attempted supportive measures are neither effective nor an option, cerebrospinal lavage can be considered as a last maneuver. A recent case report, suggested that 20-30 mL of cerebrospinal fluid can be withdrawn and replaced with 30 to 40 mL of preservative-free normal saline, Ringers lactate or Plasma-lyte via the epidural catheter.⁶¹ This intervention may shorten the recovery times, minimize potential neurotoxic insult, and reduce the incidence of postdural puncture. In light of the limited experiences and information on cerebrospinal lavage, the potential risks and benefits should be evaluated on a case-by-case basis before using this technique.

Local Anesthetic Toxicity

Local anesthetic toxicity often stems from accidental intravascular injection into epidural blood vessels. This complication can often be avoided by using careful aspiration and test dosing (Table 54-3).

For single-shot caudal, toxicity is more likely to occur when needles are advanced too far into the caudal canal or when sharp-tipped needles are used.⁶² For continuous epidural infusion, neonates and very young infants are at greater risk for local anesthetic toxicity.³ Seizures have been reported in children receiving continuous infusions of local anesthetics.^2,63 This can be avoided by using dilute solutions of local anesthetics (<0.125% bupivacaine) and by following current dosing recommendations (see local anesthetic section).⁶⁴ More important, vigilant monitoring during the administration of epidural analgesia should be a priority.

Other Adverse Effects

In a retrospective review based on a prospective collected data from 286 pediatric patients; pruritus (26.1%), nausea and vomiting (16.9%), and urinary retention (20.8%) were the most common side effects encountered during epidural anesthesia using an infusion of bupivacaine and fentanyl infusion.²⁸ Sedation and excessive block each occurred in less than 2% of patients. The incidence of respiratory depression was 4.2%, but the administration of naloxone for severe respiratory depression was never necessary. Table 54-4 summarizes the recommended treatment for the common adverse effects.

        EPIDURAL BLOCKADE FOR PEDIATRIC SURGERY (TECHNICAL)

Epidural analgesia can be delivered via a single-shot or continuous-infusion technique. These needles and catheter can be inserted at the caudal, lumbar, or thoracic level. Aspiration tests and test doses indicate possible inadvertent intravascular or intrathecal needle/catheter placement. Other advances in the field of epidural analgesia have focused on accurately positioning continuous epidural catheters. Epidural stimulation, epidural ECG, and ultrasound techniques have been developed in addition to conventional x-ray imaging to assist with accurate epidural needle/catheter placement.

Related posts:

Regional Anesthesia in the Patient with Preexisting Neurologic Disease. The History of Local Anesthesia. Stimulating Catheters. Ultrasound-Assisted Nerve Blocks in Adults. Cutaneous Blocks for the Upper Extremity. Cervical Plexus Block.

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