REGIONAL ANESTHESIA FOR PEDIATRIC PATIENTS: GENERAL CONCEPTS

Santhanam Suresh, MD FAAP
Director of Research
Children’s Memorial Hospital
Associate Professor of Anesthesiology & Pediatrics
Feinberg School of Medicine, Northwestern University
Chicago, IL
ssuresh@northwestern.edu

Giorgio Ivani, MD
Pediatric Anesthesiologist
Chairman, Division of Pediatric Anesthesia and Intensive Care
Regina Margharita Children's Hospital
Piazza Polonia 94, 10126
Turin, Italy
e-mail: gioivani@libero.it
 

• GENERAL CONCEPTS
• ANATOMICAL DIFFERENCES BETWEEN CHILDREN AND ADULTS

• ASSESSMENT AND CONSENT

• REGIONAL ANESTHESIA: AWAKE OR ASLEEP?

• PHARMACOLOGY OF LOCAL ANESTHETICS IN PEDIATRIC PATIENTS

• DOSING OF LOCAL ANESTHETICS IN PEDIATRIC PATIENTS

  • Tachyphylaxis

  • Toxicity of local anesthetic solutions

  • Specifics of local anesthetics when used in pediatric regional anesthesia

    • Bupivacaine

      • Metabolism

      • Dosage

    • Ropivacaine

      • Pharmacokinetics

    • Levobupivacaine

      • Toxicity

• ESTER-TYPE LOCAL ANESTHETICS

• TOPICAL ANESTHESIA

• REFERENCES

GENERAL CONCEPTS

Dating back to the ancient Egypt 2500 BC, the use of 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 the use of 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 30’s.4 The last two decades have had numerous studies that have demonstrated the need for analgesia in newborn children and infants.2 This resulted in significant changes and advancements 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.3 This and other related research in infants has 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 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 researches with a firm commitment for the use of regional techniques in children. Although the usual dictum that ‘children are just small adults’ may apply towards regional analgesia use in the adolescent population, it is much less applicable to infants and toddlers.

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ANATOMICAL DIFFERENCES BETWEEN CHILDREN AND ADULTS

There are significant anatomical variations between infants and older adolescents and adults. Differences in anatomy between children and adults are described in greater detail elsewhere in this text. CT guided mechanisms and the use of other imaging techniques including ultrasound have led to 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 to adults and this requires greater skill and care while placing a needle.6 Numerous formulae 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 while placing a needle in the spinal or epidural space.

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ASSESSMENT AND CONSENT

The 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 assent for children over the age of 12 years. If a child refuses to have a regional procedure done despite the parents’ insistence, it is important for the anesthesiologist to provide an alternative modality of pain relief.

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REGIONAL ANESTHESIA: AWAKE OR ASLEEP?

This has been a controversial area in adults that has recently permeated into pediatric regional anesthesia practice. The difficulty in placing a regional block in a child is the inability for the child to co-operate as well 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. While still controversial in adults, this practice has been the consensus of pediatric anesthesiologists in the USA as well as abroad.8 Prospective data collected from French group demonstrated a very low incidence of regional anesthesia related complications in children with most of them being performed in children who were under general anesthesia.9 In our practice, we attempt to place thoracic epidural catheters in the older children with response-titrated sedation. 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.

Clinical pearls

Considerations in children for regional anesthesia

• Mostly done with patient asleep

• Dose is far less than adults (calculate in mg/kg)

• Look for changes in EKG rather than physiological parameters to test dose

• Always get patient assent if the child is older

• Reported complications with regional anesthesia far less in children than adults

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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 amino-esters (esters). The amino-amides undergo enzymatic degradation by the liver while the esters are hydrolysed by plasma cholinesterases. These 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 local anesthetic solution that is used. 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 unlike the adult patient.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 a higher blood concentrations in adolescents than in adults due to increased vascular absorption14 hence caution has to be exercised in older children. Peak plasma concentrations are obtained in children in about 30 minutes after caudal blockade.15 Although clearance (CL) is similar in older children and adolescents, the steady state volume of distribution (VdSS) is increased in children when compared to adults.16 All amide local anesthetics have been shown to have diminished clearance (CL) in neonates and infants less than 3 months of age with steady maturation until they reach adults clearance at about 8 months of age. 17 The risk for 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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DOSING OF LOCAL ANESTHETICS IN PEDIATRIC PATIENTS

Most pediatric drug doses are based on the weight of the patient, Table-1. 60 This may not however be applicable to local anesthetic solution. Studies done on infants undergoing spinal anesthesia demonstrated a larger requirement of local anesthetic solution (weight –scaled) compared to their adult counterparts while using bupivacaine or tetracaine.20 However, studies on rat sciatic nerve models demonstrated similar trends in the neonatal, adolescent and adult rat.21

Table 1: Maximum recommended doses and approximate duration of action of commonly used local anesthetic agents.

Local anesthetic	Class	Max Dose (mg/kg)	Duration of action (min)
Procaine 2-Chlorprocaine Tetracaine Lidocaine Bupivacaine Ropivacaine Levobupivacaine	Ester Ester Ester Amide Amide Amide Amide	10 20 1.5 7 2-4 2-4 2-4	60-90 30-60 180-600 90-200 180-600 180-600 180-600
* When used in IV regional anesthesia, the dose of lidocaine dose should be reduced to 3 – 5 mg/kg. GO TO TOP

Tachyphylaxis: This is a clinical phenomenon whereby repeated dosing of local anesthetics lead to decreasing effects. There seems to be a correlation with 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, neurological, and allergic reactions, Table 2.60 Dose is always calculated in children on an mg/kg basis instead of predicted volumes as is done in adult regional anesthesia. Most local anesthetic solutions in children, particularly when used as continuous infusions, should have continuous monitoring of the patient for adverse effects. Toxicity of local anesthetics in children include cardiovascular22-24, central nervous system toxicity25 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 (Table 2)

Table 2: Systemic toxicity of local anesthetic solution

Central nervous system Dizziness & lightheadedness Visual & auditory disturbances Muscle twitching and tremors Generalized convulsions Cardiovascular Direct cardiac effects Depressed rapid phase of repolarization of Purkinje fibers Depressed spontaneous firing of the SA node Negative ionotrophic effect on cardiac muscle Calcium influx altered leading to decreased myocardial contractility Effects on vascular tone Low concentrations- vasoconstriction High concentrations-vasodilatation Increased pulmonary vascular resistance

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Specifics of local anesthetics when used 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 literature.27;28 It is imperative to take into consideration the use of supplemental local anesthetic solution by the surgeon as the infiltration anesthesia adds to the total dosage of local anesthetic solution in the systemic circulation. The preferred concentration for children is a 0.25% to 0.5% for peripheral nerve blocks and 0.1% for continuous infusions. Older children can tolerate a higher dose of local anesthetic solution (0.4mg/kg/hr) compared to neonates and infants (0.2mg/kg/hr).18

Metabolism: Bupivacaine is well bound to α-1 glycoprotein. Due to 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 levo and dextro-enatiomer, the dextro-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 and hence cardiac toxicity is first seen with overdosing of local anesthetic or intravascular placement.

Dosage: The dosage of bupivacaine is limited to 2 mg/kg to 4 mg/kg for a single dose injection and 0.2mg/kg to 0.4mg/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, 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 subtle increases to heart rate may go undetected.

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Ropivacaine:

This is a newer amide local anesthetic that is being used more frequently in pediatric surgery. It is a levo-enatiomer with less cardiovascular and central nervous system side effects compared to 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 when compared to bupivacaine.32 Pediatric trials have demonstrated a longer duration of action with ropivacaine than mepivacaine when used for peripheral nerve blockade.33 Caution should be exercised while using ropivacaine as well, since there are reported cases of cardiovascular toxicity with its use in children.34

Pharmacokinetics: Pharmacokinetic data is available in children on the use of ropivacaine in continuous infusions as well as for single shot injections.35-38;38 Although ropivacaine is safer in children due to its levo-enatiomer structure, caution has to be exercised since complications from intravascular injections have been reported. Alpha-1 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 due to the decreased amount of alpha- 1 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 This contributes to the greater toxicity of local anesthetics in infants and neonates when compared to older children and adults.

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Levobupivacaine:

Levobupivacaine is a newer levo-enatiomer that has fewer adverse effects than bupivacaine. Pharmacokinetic data is available in children and the dosage interval is not very different than bupivacaine.40-43 The prevalent use of levobupivacaine is not seen in children due to non-availability of the drug in the United States.

Toxicity: Levobupivacaine has been shown to be less toxic in the animal model compared to 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 to bupivacaine.

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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 which have decreased plasma cholinesterase levels, like in neonates and infants, the plasma level of these drugs may be increased leading to potentially toxic drug levels. The presence of plasma cholinesterase also limits the duration of activity of these drugs leading to shortened activity of these drugs. 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 former 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-Chlorprocaine has been used extensively in children for analgesia in the central neuraxial space.54

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TOPICAL ANESTHESIA

It is important to discuss the use of topical anesthesia in children since this 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 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 pain control for simple procedures including intravenous catheter placements.59

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

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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: 937-40

2. 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: 62-6

3. Taddio A, Katz J, Ilersich AL, Koren G: Effect of neonatal circumcision on pain response during subsequent routine vaccination [see comments]. Lancet 1997; 349: 599-603

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

5. Marhofer P, Sitzwohl C, Greher M, Kapral S: Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children. Anaesthesia 2004; 59: 642-6

6. Suresh S, Wheeler M: Practical pediatric regional anesthesia. Anesthesiol.Clin.North America. 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: 609-14

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

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: 904-12

10. Besunder JB, Reed MD, Blumer JL: 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 JB, 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: 261-86

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, Kopf GS, Covino BG: Bupivacaine for intercostal nerve blocks in children: blood concentrations and pharmacokinetics. Anesth.Analg. 1986; 65: 625-32

15. Ecoffey C, Desparmet J, Maury M, Berdeaux A, Giudicelli JF, Saint-Maurice C: Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 1985; 63: 447-8

16. Murat I, Montay G, Delleur MM, Esteve C, Saint-Maurice C: Bupivacaine pharmacokinetics during epidural anaesthesia in children. Eur.J.Anaesthesiol. 1988; 5: 113-20

17. Mazoit JX, Denson DD, Samii K: Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 1988; 68: 387-91

18. Berde CB: Toxicity of local anesthetics in infants and children. [Review]. J.Pediatr. 1993; 122: Pt 2):S14-20

19. Henderson K, Sethna NF, Berde CB: Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J Clin.Anesth. 1993; 5: 129-33

20. Frumiento C, Abajian JC, Vane DW: Spinal anesthesia for preterm infants undergoing inguinal hernia repair. Arch.Surg 2000; 135: 445-51

21. Kohane DS, Sankar WN, Shubina M, Hu D, Rifai N, Berde CB: Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine. Anesthesiology 1998; 89: 1199-208

22. Kasten GW, Martin ST: Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine. Anesth.Analg. 1985; 64: 911-6

23. Murat I, Esteve C, Montay G, Delleur MM, Gaudiche O, Saint-Maurice C: Pharmacokinetics and cardiovascular effects of bupivacaine during epidural anesthesia in children with Duchenne muscular dystrophy. Anesthesiology 1987; 67: 249-52

24. Graf BM: The cardiotoxicity of local anesthetics: the place of ropivacaine. Curr.Top.Med.Chem. 2001; 1: 207-14

25. Bergman BD, Hebl JR, Kent J, Horlocker TT: Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg. 2003; 96: 247-52, table

26. Berde CB: Convulsions associated with pediatric regional anesthesia [editorial; comment] [see comments]. Anesth.Analg. 1992; 75: 164-6

27. Ecoffey C, Desparmet J, Maury M, Berdeaux A, Giudicelli JF, Saint-Maurice C: Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 1985; 63: 447-8

28. Murat I, Montay G, Delleur MM, Esteve C, Saint-Maurice C: Bupivacaine pharmacokinetics during epidural anaesthesia in children. Eur J Anaesthesiol 1988 Mar;5(2):113-20 1988; 113-20

29. Ecoffey C, Desparmet J, Maury M, Berdeaux A, Giudicelli JF, Saint-Maurice C: Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 1985; 63: 447-8

30. Freid EB BAVR: electrocardiographic and hemodynamic changes associaed with unintentional intravascular injection of bupivacaine with epinephrine in infants. Anesthesiology 1993; 79: 394-8

31. Dony P, Dewinde V, Vanderick B, Cuignet O, Gautier P, Legrand E, Lavand'Homme P, De Kock M: The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats. Anesth.Analg. 2000; 91: 1489-92

32. Da Conceicao MJ, Coelho L: Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric patients. Br.J.Anaesth. 1998; 80: 507-8

33. Fernandez-Guisasola J, Andueza A, Burgos E, Plaza A, Porras MC, Reboto P, Rivera JC, del Valle SG: A comparison of 0.5% ropivacaine and 1% mepivacaine for sciatic nerve block in the popliteal fossa. Acta Anaesthesiol.Scand. 2001; 45: 967-70

34. Petitjeans F, Mion G, Puidupin M, Tourtier JP, Hutson C, Saissy JM: Tachycardia and convulsions induced by accidental intravascular ropivacaine injection during sciatic block. Acta Anaesthesiol.Scand. 2002; 46: 616-7

35. Ivani G, Mereto N, Lampugnani E, Negri PD, Torre M, Mattioli G, Jasonni V, Lonnqvist PA: Ropivacaine in paediatric surgery: preliminary results. Paediatr Anaesth 1998; 8: 127-9

36. Ivani G, Mazzarello G, Lampugnani E, DeNegri P, Torre M, Lonnqvist PA: Ropivacaine for central blocks in children. Anaesthesia 1998; 53: Suppl-6

37. Ala-Kokko TI, Partanen A, Karinen J, Kiviluoma K, Alahuhta S: Pharmacokinetics of 0.2% ropivacaine and 0.2% bupivacaine following caudal blocks in children. Acta Anaesthesiol Scand. 2000; 44: 1099-102

38. Dalens B, Ecoffey C, Joly A, Giaufre E, Gustafsson U, Huledal G, Larsson LE: Pharmacokinetics and analgesic effect of ropivacaine following ilioinguinal/iliohypogastric nerve block in children. Paediatr.Anaesth. 2001; 11: 415-20

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

40. Ivani G, De Negri P, Lonnqvist PA, Eksborg S, Mossetti V, Grossetti R, Italiano S, Rosso F, Tonetti F, Codipietro L: A comparison of three different concentrations of levobupivacaine for caudal block in children. Anesth.Analg. 2003; 97: 368-71, table

41. Lerman J, Nolan J, Eyres R, Schily M, Stoddart P, Bolton CM, Mazzeo F, Wolf AR: Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: a multicenter trial. Anesthesiology 2003; 99: 1166-74

42. Ala-Kokko TI, Raiha E, Karinen J, Kiviluoma K, Alahuhta S: 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: 551-79

44. Mather LE, Huang YF, Veering B, Pryor ME: Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep. Anesth.Analg. 1998; 86: 805-11

45. Tobias JD, O'Dell N: Chloroprocaine for epidural anesthesia in infants and children. AANA.J. 1995; 63: 131-5

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: 307-14

47. Tobias JD, Rasmussen GE, Holcomb GW 3rd, Brock JW 3rd, - Morgan WM 3rd: Continuous caudal anaesthesia with chloroprocaine as an adjunct to general anaesthesia in neonates. - Can J Anaesth 1996 Jan;43(1):69-72 1996; 69-72

48. Crowhust JA: Cholinesterase deficiency. Anaesth.Intensive Care 1983; 11: 79

49. Kuhnert BR, Philipson EH, Pimental R, Kuhnert PM: A prolonged chloroprocaine epidural block in a postpartum patient with abnormal pseudocholinesterase. Anesthesiology 1982; 56: 477-8

50. Monedero P, Hess P: High epidural block with chloroprocaine in a parturient with low pseudocholinesterase activity. Can.J.Anaesth. 2001; 48: 318-9

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: 21-5

52. Henderson K, Sethna NF, Berde CB: Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. J.Clin.Anesth. 1993; 5: 129-33

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. Journal.of.Clinical.Anesthesia. 1993; 5: 129-33

55. Acharya AB, Bustani PC, Phillips JD, Taub NA, Beattie RM: Randomised controlled trial of eutectic mixture of local anaesthetics cream for venepuncture 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: 850-3

57. Gourrier E, Karoubi P, el Hanache A, Merbouche S, Mouchnino G, Leraillez J: Use of EMLA cream in a department of neonatology. Pain 1996; 68: 431-4

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: 1093-9

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: 403-8

60. Suresh S, Cote CJ: Local anesthetics for infants and children, Neonatal and Pediatric Pharmacology, Therapeutic Priciples in Practice, 3 Edition. Edited by Yaffe SJ, Aranda JV. Philadelphia, Lippincott Williams & Wilkins, 2004, pp 663-8

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