New york school of regional anesthesia

Dating back to ancient Egypt of 2500 bc, regional anesthesia was emphasized for circumcision. Traditional Chinese medicine has touted the use of needles and acupuncture for pain management for centuries. August Bier reported in 1899 the first study on regional anesthesia in children. This was followed by a report by Bainbridge on the use of spinal anesthesia in children.1 The use of caudal analgesia in children was described in the urology literature in the early 1930s.2 In the last two decades, numerous studies have demonstrated the need for analgesia in newborn children and infants.3 This has resulted in significant changes and advances in clinical anesthesia care for infants, children, and adolescents. In particular, the decrease in stress has resulted in better outcomes in infants and children. Infants exposed to significant pain in the neonatal period may experience bio-behavioral changes with advancing age.4 This and other related research have led the medical community to consider the use of adequate analgesia in infants. Although research in regional anesthesia in adults continues to be performed and is written about prolifically in literature, there seems to be a relative lack of publications in regional anesthesia in children.Most work in regional anesthesia has been carried out by few researchers with a firm commitment to the use of regional techniques in children. Although the usual dictum that children are just small adults may apply to regional analgesia in the adolescent population, it ismuch less applicable to infants and toddlers.

Anatomic Differences Between Children & Adults

Significant anatomic variations exist between infants and older adolescents and adults. Differences in anatomy between children and adults are described in greater detail elsewhere in this chapter. CT-guided mechanisms and the use of other imaging techniques including ultrasound have led to a better understanding of the anatomy of infants and children.5 This has facilitated a more accurate placement of needles in children with less risk of complications. The epidural space is superficial compared with that in adults, and this requires greater skill and care while placing a needle.6 Numerous formulas are available for estimating the distance of the epidural space from the skin.6 However, this should not alter the judgment of the skilled anesthesiologist placing a needle in the spinal or epidural space.

Assessment & Consent

Parents typically provide consent for a procedure for their child.However, if the child has the cognitive ability to discern right from wrong, it is suggested that the child’s consent for performance of a regional technique be obtained as well.7 There is growing debate as to when or what this age may be. We routinely obtain consent for children over the age of 12 years. If a child refuses to have a regional procedure despite the parents’ insistence, it is important for the anesthesiologist to provide an alternative modality of pain relief.

Regional Anesthesia: Awake or Asleep?

Whether the patient is awake or asleep during regional anesthesia has been a controversial area in adults, which has recently permeated into pediatric regional anesthesia practice. Thedifficulty inplacing a regional block ina child is the inability of the child to cooperate aswell as the cognitive inability of the child to relate to symptoms such as paresthesia or pain.We feel that the child is best provided with a regional technique under deep sedation or after induction of general anesthesia. Although still controversial in adults, this practice has been the consensus of pediatric anesthesiologists in theU.S. as well as abroad.8 Prospective data collected fromthe French group demonstrated a very low incidence of regional anesthesi arelated complications in children, with most of them being performedin childrenwhowere under general anesthesia.9 In our practice, we attempt to place thoracic epidural catheters in the older childrenwith response-titratedsedation. All other regional techniques are carried out under heavy sedation or under general anesthesia. As more regional techniques are being performed in children, we will have greater insight into associated complications.

Pharmacology of Local Anesthetics in Pediatric Patients

The two main classes of local anesthetics used in infants and children include the amino-amides (amides) and the aminoesters (esters). The amino-amides undergo enzymatic degradationby the liver,whereas the esters arehydrolyzedby plasma cholinesterases. These actionsmay 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 local anesthetic solution that are 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 of local 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 3months of age,with steady maturation until they reach adult clearance at about 8months 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

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Most pediatric drug doses are based on the weight of the patient60 (Table 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

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.1

Toxicity of Local Anesthetic Solutions

Toxicity of local anesthetics solution 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 most local anesthetic solutions, particularly when used as continuous infusions, should be monitored continuously for adverse effects. Toxicities of local anesthetics in children include cardiovascular[22–24] and central nervous system toxicities25 and allergic reactions to ester local anesthetic solutions. The risk of toxicity can be largely avoided by limiting the local anesthetic dosage in children[26] (see Table 2).

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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 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 of local 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 iswellboundtoα-1 glycoprotein. Because of low levels of albumin and α-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 of local 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 usedmore frequently in pediatric surgery. It is a l-enantiomer with less 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 comparedwith that of bupivacaine.32 Pediatric trials have demonstrated a longer duration of actionwith ropivacaine thanwith mepivacainewhenused 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.35–38,39 Although ropivacaine is safer in children owing to its l-enantiomer structure, caution must be exercised because complications from intravascular injections have been reported. α1-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 α1-acid glycoprotein. This facilitates the metabolism of local 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 of levobupivacaine is not seen in children owing to nonavailability of the drug in the U.S.

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.

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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

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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 othermodalities for pain control including iontophoretic local anesthetic drug delivery can be used for pain control in simple procedures including intravenous catheter placements.59

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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.

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