Local Anesthetic Drugs
Local analgesic drugs are now very widely used in children, particularly in the management of postoperative pain ( Table 5-1 ).
| Local Anesthetic | Dose (mg/kg) |
|---|---|
| Bupivacaine † Plain or with epinephrine | 2.5 |
| Ropivacaine † and levobupivacaine † | 3.0 |
| Lidocaine † Without epinephrine With epinephrine | 4.5 7 |
| Mepivacaine † or prilocaine † Without epinephrine | 5 7 |
| Tetracaine | 1.5 |
| Procaine | 10 |
| 2-chloroprocaine ‡ | 20 |
* Maximum dose may depend on site of injection.
† Doses for continuous infusions of amides should be reduced by 30% in infants <6 mos.
Clinical Pharmacology
Local analgesic drugs are amino esters (procaine, chloroprocaine, tetracaine) or amino amides (lidocaine, bupivacaine, ropivacaine) that interrupt nerve conduction by blocking sodium channels.
The pharmacokinetics in infants differ from those in older children and adults:
- 1.
Absorption of the drugs is rapid, the cardiac output and regional tissue blood flows are greater, and the epidural space contains less fat tissue to buffer uptake. Drugs sprayed into the airway are very rapidly absorbed.
- 2.
The volume of distribution of the drug is larger. Plasma levels of bupivacaine after administration of a 2.5 mg/kg dose into the epidural space in infants are therefore significantly less than in young children and adults. This greater volume of distribution also prolongs the elimination half-life.
- 3.
The extent of protein binding in the neonate is less than in children because serum albumin and α 1 -acid glycoprotein levels are reduced. Bilirubin, which binds to the acidic sites on albumin, does not interfere with bupivacaine binding as the latter binds to the basic binding sites.
- 4.
The rate of metabolism of local analgesic drugs is reduced in very young infants:
- a.
Plasma cholinesterase activity is reduced, which may prolong the metabolism of the ester type of drugs. For example, the plasma half-life of ester anesthetics is extended in the neonate. This is probably clinically insignificant.
- b.
The hepatic pathways (cytochrome P450) for conjugation of the amide local analgesics are immature. The neonate has a reduced capacity to metabolize bupivacaine; clearance at 1 month of age is only one third of adult rates, although, by 9 months, clearance reaches adults rates. This may lead to clinical problems in neonates during prolonged infusions of bupivacaine (i.e., limit infusions to 48 hours at 0.2 mg/kg/hr). Older infants and children metabolize drugs much more rapidly because of their relatively large liver size.
- 5.
The metabolism of prilocaine may result in methemoglobinemia. This may be more important in infants with reduced levels of the enzyme methemoglobin reductase, and may be significant if large areas of skin are covered with EMLA cream.
Local Anesthetic Drugs
Lidocaine
Lidocaine is commonly used for local infiltration. Total dose should not exceed 4.5 mg/kg of the plain solution or 7 mg/kg if epinephrine is added. Epinephrine prolongs the block and decreases the peak serum concentration by about 40%.
Bupivacaine
Bupivacaine is a racemic mixture; the levo form is the clinically active form and the dextro form is the more toxic form. It has been widely used for peripheral and epidural blocks. It has the disadvantage that overdosing or accidental intravascular injection may lead to severe myocardial depression that may be prolonged and difficult to reverse (see Intralipid). Bupivacaine metabolism is reduced in small infants requiring close attention to dose (see Clinical Pharmacology). The addition of epinephrine to bupivacaine is less effective in prolonging the block and decreasing peak serum concentration than it is for lidocaine. However, epinephrine does extend the duration of action of bupivacaine to a greater extent in infants and young children than in older children.
Levobupivacaine
Levobupivacaine is the levo enantiomer of bupivacaine. It is less cardiotoxic, approximately 20% more potent than bupivacaine and may be more suitable for prolonged infusions.
Ropivacaine
Ropivacaine is also a levo enantiomer, but of the racemate termed ropivacaine. It too is less cardiotoxic than bupivacaine and produces an equal sensory block with a more rapid onset, less motor block, but similar duration of effect. It has gained popularity as an agent for caudal analgesia. Compared with bupivacaine, ropivacaine is less rapidly absorbed from the caudal epidural space, and peak plasma levels are less after an ilioinguinal nerve block. Ropivacaine should not be used for penile or digital nerve blocks as vasoconstriction and ischemia have been reported . Epinephrine does not prolong the duration of an epidural or other blocks with ropivacaine.
Toxicity
Maximum dosages of local anesthetics have been recommended to prevent overdoses (see Table 5-1 ).
Compared with adults, neonates may exhibit signs of central nervous system toxicity (jitteriness and seizures) at lower blood levels of a drug. Local analgesic blocks in children are commonly performed during general anesthesia. This practice tends to mask any signs of neurologic toxicity, but depending upon the anesthesia agent used might increase cardiac toxicity. If seizures occur, 100% oxygen should be administered, the airway secured, and medication to stop the seizure administered immediately: intravenous benzodiazepine (i.e., midazolam 0.05 to 0.2 mg/kg), thiopental (2 to 3 mg/kg), or propofol (1 to 2 mg/kg) in repeated doses as required. Because potent inhalational anesthetics (e.g., halothane) may augment the cardiac effects of the local anesthetic drugs, caution is advised.
N.B. Acute intravascular (intravenous or intraosseous) injection of bupivacaine (and less likely ropivacaine or levobupivacaine) may cause ventricular tachycardia and difficulty restoring normal sinus rhythm, both resulting in a low cardiac output state. To date, no pharmacologic intervention has reversed these cardiac effects of local anesthetics. However, anecdotal reports in adults and studies in animals suggest a role for intravenous Intralipid (20%) at 1 ml/kg loading dose followed by either 1 ml/kg every 3 to 5 minutes (total of 3 ml/kg) or an infusion of 0.25 to 0.5 ml/kg/min after an acute intravascular overdose of bupivacaine (and other local anesthetics) with acute myocardial dysfunction. The mechanism is believed to be elution of the local anesthetic from the myocardium by the lipid. To date, only one case reported successful recovery in a child given a toxic dose of bupivacaine. ( N.B. Propofol should not be substituted for Intralipid if the latter is not available to resuscitate a local anesthetic toxicity.)
Intravenous lidocaine in normal doses may produce toxic effects in children with right-to-left cardiac shunting because the normal first-pass absorption within the pulmonary circulation is bypassed. The dose should be reduced by at least 50% in such cases.
Adjuvant Drugs
Epinephrine
Epinephrine is added to local anesthetic drugs to extend their duration of action, and to limit absorption of the drug into the intravascular space. It also acts as a marker for intravascular injection; peaked T waves and ST segment elevation are more reliable signs of intravascular injection than tachycardia, although this also may depend on the inhalational anesthetic administered. Certainly, tachycardia may be more difficult to assess and therefore is less sensitive a warning sign in children. Epinephrine may interact with halothane and precipitate arrhythmias, but doses up to 10 µg/kg by infiltration are considered safe in children.
Clonidine
Clonidine (1 to 2 μg/ml) may be added to local anesthetics for use in the caudal/epidural space. This will prolong the effect of the block approximately 3 hours (based on a systematic review), but has inconsistent effects on the rate of elimination of the local analgesic from the epidural space.
Apnea has been reported after epidural clonidine administration in preterm infants, although three toddlers who received a 100 fold overdose of clonidine experienced only prolonged postoperative sedation and no respiratory distress/apnea. Clonidine may also contribute to postoperative sedation (usually at doses >2 µg/kg) and this may be undesirable in outpatients.
Suggested Reading
Regional Analgesia For Pain Control
Regional analgesia techniques alone are of limited value during pediatric surgical procedures; the overall nonacceptance and lack of cooperation in the awake young child results in the need for such large doses of sedatives that general anesthesia usually becomes preferable. However, in the management of postoperative pain, regional analgesic techniques have become an indispensable part of our pediatric anesthesia practice (see later discussion).
Regional analgesia may provide acceptable pain control intraoperatively for some selected children:
- 1.
Spinal and/or epidural anesthesia is useful for small infants, especially for the preterm infant with or without lung disease for herniotomy, circumcision, or lower abdominal surgery. This is a means of reducing, but not eliminating the probability of postoperative apnea.
- 2.
Epidural analgesia may be a suitable alternative to general anesthesia in some older children (e.g., those with cystic fibrosis), and it may then be continued into the postoperative period.
- 3.
Some older children (5 years of age and older) can be charmed into cooperation and have their upper limb fractures reduced under a regional block.
- 4.
Intravenous regional analgesia (Bier block) can be used for some older children having superficial surgery to lesions on the distal limbs or for some fracture reductions. (Extreme caution must be exercised if a plaster cast is applied to an exsanguinated limb).
- 5.
The possibility of using regional or local infiltration analgesia (see Table 5-1 ) should also be considered for any minor procedure in a high-risk patient (e.g., skeletal muscle biopsy in a child with cardiomyopathy, lymph node biopsy in a child with a mediastinal mass).
Rarely, regional blocks are also indicated for chronic pain therapy and/or diagnostic purposes.
Basic rules for regional analgesia are as follows:
- 1.
Calculate the allowable weight-based dose of the local analgesic agent for each child and do not exceed that dose.
- 2.
Use as much of the allowable dose of agent as is necessary to ensure a good block.
- 3.
Use careful aseptic technique; beware of intravascular injection. Test by aspirating frequently.
- 4.
Plan ahead; allow a generous period for the block to become well established before allowing the surgeon to approach the child.
- 5.
Remember the special considerations for the use of local analgesic drugs in infants and young children (see previous discussion).
- 6.
Always be prepared to deal with the complications of regional analgesia. Drugs and equipment to induce general anesthesia, secure the airway, and ventilate the lungs must be immediately available. Establish IV access before the block. A source of Intralipid should be immediately available to treat an intravascular injection of local anesthetic (see Toxicity).
- 7.
Be prepared; unsatisfactory regional analgesia may require administration of general anesthesia to permit completion of the surgical procedure.
- 8.
If possible, apply topical anesthetic cream over the site of the proposed initial needle insertion point (see page 634).
- 9.
Children are generally upset by paresthesias; techniques that do not rely on eliciting these effects are preferred.
- 10.
The use of ultrasound has been demonstrated to be very effective in accurately placing the local analgesic solution. This technique should be applied whenever possible.
- 11.
Supplement your regional technique with age-appropriate sedation (e.g., oral midazolam), systemic analgesics (e.g., fentanyl intravenously), and distraction (i.e., video or transistor radio and earphones).
- 12.
The consensus of pediatric anesthesiologists is that it is acceptable standard practice to perform a caudal or lumbar epidural block including passing an indwelling catheter in an anesthetized child. Children will not lie still to have the catheter inserted while they are awake or sedated. The risks of inserting the block under general anesthesia are considered less than the risks of inserting it in a distressed and mobile awake child.
- 13.
When a choice exists, peripheral nerve blocks are generally safer than neuraxial blocks in infants and children.
- 14.
Do not use epinephrine for blocks of areas with inadequate collateral blood supply (digits, penis).
- 15.
Do not administer sedatives to former preterm infants with a spinal or epidural as this will markedly increase the potential for apnea.
Suggested Reading
An Outline Of Procedures For Regional Blocks in Infants and Children
For more detailed descriptions of the anatomic considerations and techniques of regional nerve blocks, the reader is referred to standard textbooks.
Awake Spinal Analgesia for Infants
In infants, awake spinal analgesia is most commonly indicated for surgery at or below the umbilicus, but it has also been used for upper abdominal surgery in small infants with a history of respiratory disease. It avoids the necessity to intubate and ventilate the lungs and therefore reduces the risk of additional airway damage or ventilator dependence. Very little change in blood pressure occurs in infants or children after spinal block. Postoperative apnea of the former preterm infant is less common after spinal analgesia but is still a risk. Supplemental sedation will increase the potential for apnea.
Special Considerations
- 1.
The spinal cord may extend to as low as L3 in the infant (compared with L1–2 in the older child or adult), so perform the lumbar puncture at L4–5.
- 2.
The dural space extends to S3–4 in the neonate.
- 3.
The volume of cerebrospinal fluid (CSF) in infants (4 ml/kg) is relatively greater than in adults (2 ml/kg).
Contraindications
- 1.
Sepsis or infected lumbar puncture site.
- 2.
Coagulopathy.
- 3.
Lack of enthusiastic parental consent.
Anesthetic Management
Preoperative
- 1.
The child should be fasted as for general anesthesia.
- 2.
No premedication is necessary for small infants.
Perioperative
- 1.
Observe all special precautions for infants, both term and preterm. Prepare the anesthesia machine, endotracheal tubes, and all ancillary equipment.
- 2.
A brandy-and-sugar soother is often useful to settle the infant. (Glucose may have analgesic properties of its own in neonates.) Sedatives such as ketamine or midazolam that supplement a spinal will cause a similar incidence of apnea as general anesthesia.
- 3.
Establish a reliable intravenous infusion using local analgesia in the lower extremity.
- 4.
Scrub, glove, and sterilize the skin.
- 5.
Instruct your assistant to gently but firmly restrain the child in the chosen lateral or sitting position, but avoid neck flexion, which may compromise the airway.
- 6.
Prepare and drape the child. Infiltrate the skin over the L4–5 interspace with 1% lidocaine.
- 7.
Prepare a neonatal spinal needle (e.g., 22 or 25-gauge, 1 inch [26 mm] long) and measure the dead space of this needle with the use of a tuberculin syringe.
- 8.
Prepare a syringe containing 0.4 to 1.0 mg/kg of 1% tetracaine mixed with an equal volume of 10% dextrose, plus a volume of this mixture equal to the dead space of the needle (approximately 0.2 ml). For upper abdominal/thoracic surgery, 1 mg/kg of tetracaine (1%) or bupivacaine (0.5% to 0.75%) in preterm infants (<4 kg).
- 9.
Insert the needle at L4–5 with the bevel facing laterally until CSF is obtained.
- 10.
Slowly inject the local analgesic solution; rapid injection may result in a high or total spinal.
- 11.
Carefully return the infant to the supine position and place the pulse oximeter and blood pressure cuff on the lower extremity. Motor function in lower limbs usually ceases immediately. Do not allow the child’s legs to be raised (e.g., to apply the cautery pad) or an excessively high level block may result.
- 12.
Duration of anesthesia is usually about 1.5 hours.
- 13.
N.B. Total spinal anesthesia in infants is heralded by apnea with little change in blood pressure. Treat with controlled ventilation until recovery occurs.
Perioperative
- 1.
Continue to nurse the child in the horizontal position until motor function in the legs returns.
- 2.
Monitor the infant born prematurely carefully for apnea; it is less common than after general anesthesia but may occur.
Suggested Reading
Caudal Block
The caudal block is very useful in infants and children; it provides good postoperative analgesia after abdominal, lower limb, or perineal surgery. Caudal analgesia has also been used as an alternative to spinal analgesia for lower abdominal surgery in infants. In young infants, the contents of the epidural space offer little resistance to the spread of local analgesic solutions. In this age group, epidural analgesia is accompanied by very little change in blood pressure or cardiac output. Continuous caudal catheters have been used intraoperatively for more prolonged surgery, and they may safely be threaded to a surprising distance cephalad (T6). Local infection has not been a problem when catheters have been left in situ for 3 days.
Caudal morphine provides analgesia for thoracic and abdominal procedures and reduces the need for systemic analgesic drugs. However, caudal opioids are associated with side effects that include nausea, vomiting, and rarely respiratory depression; hence this regime is unsuitable for outpatients and for infants.
Preferred Technique
For postoperative analgesia, the block should be performed after general anesthesia has been induced but before the surgery commences. This allows for the block to become well established during surgery, offers the potential for preemptive analgesia, permits a reduction in general anesthetic agents, and allows a more rapid awakening.
The child is placed in the lateral decubitus position with the upper knee and hip well flexed. The landmarks are then identified ( Figure 5-1 ): the tip of the coccyx to fix the midline and the sacral cornua bounding the sacral hiatus. These lie at the apex of an inverted equilateral triangle, the base of which is a line drawn between the posterior superior iliac spines. The child is carefully prepared and draped, and the operator wears gloves and a mask. The skin over the sacral hiatus is nicked with an 18-gauge needle (to avoid tracking epidermal tissues into the caudal canal), after which an IV catheter (22 gauge for children <2 yr, 20 gauge for those >2 yr) is advanced cephalad at an angle of 45° to the skin with the bevel facing anteriorly. A distinctive sudden “give” is felt as the needle passes through the sacrococcygeal ligament. At this point, the angle of the needle is reduced and the catheter only is advanced into the caudal canal ( Figure 5-2 ). The needle is then withdrawn, leaving the intravenous catheter in the caudal/epidural space. The catheter should be observed for passive reflux of blood or CSF. If there is no evidence of blood or CSF, the local anesthetic may be injected slowly in incremental doses (there should be no resistance to injection; if there is resistance, then the catheter is either kinked or misplaced) while the electrocardiogram is observed. Changes in QRS pattern and/or peaked T waves may be an early sign of intravascular injection. A finger should be placed over the sacrum to detect inadvertent subcutaneous injection. Advancing an intravenous catheter rather than a needle diminishes the risk of an intravascular or intraosseous injection, even if the child moves. Some advocate listening over the lower lumbar spine with a stethoscope during the injection of local anesthetic to auscultate a “Swoosh” with a successful caudal insertion.
