Clinical review

Recent advances: Paediatric anaesthesia

^a Department of Anaesthesia, Royal Hospital for Sick Children, Edinburgh EH9 1LF

Correspondence to: Dr Doyle

	Introduction

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

About one quarter of the population are aged under 15 years and many of them will require anaesthesia and surgery. Several recent developments have contributed to making anaesthesia for children easier, safer, and more pleasant for the child and parents.

	Topical cutaneous anaesthesia

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

One of the most unpleasant procedures for children in hospital is insertion of a venous cannula for induction of anaesthesia, taking blood samples, or administering fluid and drugs. To try to reduce the pain associated with the procedure a topically active local anaesthetic preparation is applied such as Emla cream (a mixture of 2.5 mg/ml of lignocaine and 2.5 mg/ml of prilocaine). To work properly Emla cream has to be applied at least an hour before the procedure,^{1 2} which means it is not suitable for emergency and some day case patients. Even when applied for 60 minutes it is effective in only 65% of children,³ although this proportion rises if it is left in place for 90-120 minutes.⁴ Emla cream also causes vasoconstriction at the site of application, which can make venepuncture difficult.⁵

The recent development and licensing of a topical cream made with the local anaesthetic amethocaine has greatly improved topical anaesthesia. Amethocaine has a much higher lipid solubility than Emla and penetrates the stratum corneum, the main barrier to absorption of drugs through the skin, with comparative ease. A gel containing 4% amethocaine has been shown to provide analgesia for venous cannulation in over 80% of children compared with 66% of children who had Emla cream applied for the same period.⁶ This makes amethocaine particularly useful in outpatient day case surgery. Amethocaine has also been found to cause erythema and vasodilatation at the site of application, which may facilitate venous cannulation.⁷

	Sevoflurane

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

One of the ways in which paediatric anaesthesia differs from adult anaesthesia is that inhalational induction is used much more commonly. The characteristics of the volatile anaesthetic agent used are important. It needs to induce anaesthesia quickly, have a low incidence of complications such as coughing, laryngospasm, and hypoxia during induction, and allow rapid recovery. Until recently halothane was the most commonly used agent, and this generally results in smooth, trouble free inductions. However, a new agent, sevoflurane, is now available in Britain which has very low solubility in blood (the blood-gas partition coefficient is 0.47 compared with 2.1 for halothane). Studies have shown that it induces anaesthesia more rapidly than halothane,^{8 9 10 11 12} and it is also eliminated more quickly from the blood, producing a faster recovery.^{10 11 12 13 14}

View larger version (100K): [in this window] [in a new window]   Inhalational anaesthesia: sevoflurane is replacing halothane. FRASER/FREEMAN HOSPITAL/SPL

Sevoflurane has a pleasant smell and is the least irritant of the volatile agents to the respiratory tract. There is a low incidence of respiratory tract irritation during its use.^{15 16} It produces similar degrees of myocardial depression and hypotension to equipotent concentrations of halothane in children¹⁰ and less sensitisation of the myocardium to catecholamines.¹⁷ The degree of respiratory depression is similar to that produced by halothane at equipotent concentrations.^{18 19}

Halothane hepatitis
Repeated administration of halothane occasionally results in halothane hepatitis. This can develop into hepatic necrosis, which may be fatal. The condition is probably caused by hapten formation with the trifluoroacetic acid metabolite of halothane and the subsequent production of antibodies and free radicals toxic to the liver. Halothane hepatitis is less common in children than adults^{20 21} but is nevertheless important.²² Since sevoflurane is metabolised to a much lesser extent than halothane (3.3% compared with 20%) and the metabolite trifluoroacetic acid is not produced,²³ the problem of halothane hepatitis should be significantly reduced or eliminated. The degree of hapten formation with the sevoflurane metabolite hexafluoroisopropanol is much less than with trifluoroacetic acid and no free radical production has been found.¹⁶ Only four cases of hepatotoxicity attributable to sevoflurane have been reported in over two million administrations.²⁴

The low toxicity of sevoflurane makes it particularly useful in children since they often require repeated inhalational anaesthesia for multiple procedures carried out close together. The other available volatile anaesthetic agents, enflurane and isoflurane, are not suitable for routine inhalational induction of anaesthesia and are associated with a higher incidence of perioperative complications than halothane.^{25 26} A drug which combines rapid trouble free induction of anaesthesia with minimal risk of hepatic damage during repeated administrations is thus a welcome advance in safety.

	Caudal epidural blockade

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

Epidural analgesia using a single injection of local anaesthetic to the epidural space via the caudal approach combines the advantages of a simple technique with a high success rate and is one of the commonest local anaesthetic techniques used in children. The technique has a wide range of indications in paediatric practice including orchidopexy, circumcision, and inguinal herniotomy as well as lower limb and pelvic orthopaedic surgery and lower abdominal surgery in neonates and infants. Its main disadvantage is the short duration of action, and even long acting local anaesthetic drugs such as bupivacaine will reliably provide analgesia for only three to four hours.²⁷ Various additives to local anaesthetic solutions have been used to try to prolong the duration of caudal analgesia provided by a single injection. Opioids mixed with the local anaesthetic are effective at prolonging the duration of caudal epidural analgesia²⁸ but concerns about late respiratory depression mean that they can be used only for patients who are going to be nursed in a high dependency setting.

Alternative additives which are currently being investigated include clonidine and ketamine. Clonidine is an 2 adrenergic receptor agonist, a class of drug which is widely used in medicine and anaesthesia as an antihypertensive, sedative, premedicant, and analgesic. Clonidine probably induces analgesia when administered epidurally by stimulating the descending noradrenergic medullospinal pathways. These inhibit the release of nociceptive neurotransmitters in the dorsal horn of the spinal cord. Ketamine hydrochloride is widely used for anaesthesia and analgesia in children. It acts as an antagonist at the subset of glutamate receptors stimulated by the agonist N-methyl d-aspartate (NMDA). NMDA receptors are found throughout the central nervous system including the lumbar spinal cord. As well as producing analgesia after systemic administration ketamine exerts profound analgesic actions at the spinal cord level in animal preparations.^{29 30} This feature, together with the minimal respiratory depressant effects of ketamine, has stimulated clinical interest in the epidural administration of ketamine to provide postoperative analgesia.

Clonidine and ketamine have both been shown to prolong the duration of the local anaesthetic bupivacaine when used to provide caudal epidural analgesia. The median duration of caudal epidural analgesia with 0.25% bupivacaine is prolonged from 3-4 hours to 9-16 hours when 1-2 µg/kg of clonidine is added to the local anaesthetic solution.^{31 32} Similarly, ketamine combined with 0.25% bupivacaine significantly prolongs the median duration of a single shot caudal epidural blockade to 12.5 hours.^{33 34} The optimal dose of ketamine for prolonging caudal epidural blockade in children has been shown to be 0.5 mg/kg.³⁵ No differences have been found between children receiving caudal epidural clonidine or ketamine and control groups in the occurrence of side effects such as significant haemodynamic changes, respiratory depression, motor block, urinary retention, or postoperative sedation.^{31 32 33 34 35}

Until new longer acting local anaesthetics that can selectively block sensory rather than motor and autonomic fibres are developed the use of additives is likely to continue. Clonidine and ketamine offer the potential to prolong the duration of single shot caudal injections with minimal risk of side effects. Further studies are needed, however, to compare the optimum regimens of these two additives and to obtain a more complete picture of their benefits and the incidence of side effects in children.

	Conclusion

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

The three developments described here illustrate the ways in whove issues are as important. The need for and use of topical cutaneous analgesia is rare in adults and inhalational induction of anaesthesia is also unusual. Caudal epidural analgesia has far fewer indications in adults than children, although the additives described may also prove useful in epidural infusions of local anaesthetic and subarachnoid (spinal) anaesthesia.

	References

Top Introduction Topical cutaneous anaesthesia Sevoflurane Caudal epidural blockade Conclusion References

1. Hallen B, Olsson GL, Uppfeldt A. Pain-free venepuncture. Effect of timing of application of local anaesthetic cream. Anaesthesia 1984;39:969-72. [Medline]
2. Manner T, Kanto J, Lisalo E, Lindberg R, Vinamaki O, Scheinin M. Reduction of pain at venous cannulation in children with a eutectic mixture of lidocaine and prilocaine (EMLA cream): comparison with placebo cream and no local premedication. Acta Anaesthesiol Scand 1987;31:735-9.
3. Ehrenstrom-Reiz G, Reiz S, Stockman O. Topical anaesthesia with EMLA, a new lidocaine-prilocaine cream and the cusum technique for detection of minimal application time. Acta Anaesthesiol Scand 1983;27:510-2.
4. Bjerring P, Arendt-Nielson L. Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream. Br J Anaesth 1990;64:173-7. [Abstract/Free Full Text]
5. Bjerring P, Andersen PH, Arendt-Nielsen L. Vascular response of human skin after analgesia with EMLA cream. Br J Anaesth 1989;63:655-60.
6. Lawson RA, Smart NG, Gudgeon AC, Morton NS. Evaluation of an amethocaine gel preparation for percutaneous analgesia before venous cannulation in children. Br J Anaesth 1995;75:282-5.
7. Doyle E, Freeman J, Im NT, Morton NS. An evaluation of a new preparation of amethocaine for topical anaesthesia prior to venepuncture in children. Anaesthesia 1993;48:1050-2. [Medline]
8. Black A, Sury MRJ, Hemington L, Howard R, Mackersie A, Hatch DJ. A comparison of the induction characteristics of sevoflurane and halothane in children. Anaesthesia 1996;51:539-42. [Medline]
9. Lerman J, Davis PJ, Welborn LG, Orr RJ, Rabb M, Carpenter R, et al. Induction, recovery and safety characteristics of sevoflurane in children undergoing ambulatory surgery. Anesthesiology 1996;84:1332-40. [Medline]
10. Piat V, Dubois MC, Johanet S, Murat I. Induction and recovery characteristics and hemodynamic responses to sevoflurane and halothane in children. Anesth Analgesia 1994;79:840-4. [Abstract/Free Full Text]
11. Naito Y, Tamai S, Shinghu K, Fujimori R, Mori K. Comparison between sevoflurane and halothane for paediatric ambulatory surgery Br J Anaesth 1991;67:387-9. [Abstract/Free Full Text]
12. Sarner JB, Levine M, Davis PJ, Lerman J, Cook DR, Motoyama EK. Clinical characteristics of sevoflurane in children. Anesthesiology 1995;82:38-46. [Medline]
13. Sury MRJ, Black A, Hemington L, Howard R, Hatch DJ, Mackersie A. A comparison of the recovery characteristics of sevoflurane and halothane in children. Anaesthesia 1996;51:543-6. [Medline]
14. Landais A, Saint-Maurice C, Hamza J, Robichon J, McGee K. Sevoflurane elimination kinetics in children. Paediatr Anaesth 1995;5:297-301.
15. Eger EI. New inhalational agents desflurane and sevoflurane. Can J Anaesth 1993;40:R3-5.
16. Frink EJ, Brown BR. Sevoflurane. Anesth Pharmacol Rev 1994;2:61-7.
17. Imamura S, Ikeda K. Comparison of the epinephrine-induced arrhythmogenic effect of sevoflurane with isoflurane and halothane. J Anaesth 1987;1:62-8.
18. Doi M, Ikeda K. Respiratory effects of sevoflurane. Anesth Analgesia 1987;66:241-4. [Abstract/Free Full Text]
19. Mori N, Suzuki M. Sevoflurane in paediatric anaesthesia: effects on respiration and circulation during induction and recovery. Paediatr Anaesth 1996;6:95-102. [Medline]
20. Wark HJ. Post-operative jaundice in children. The influence of halothane. Anaesthesia 1983;38:237-42.
21. Warner LO, Beach TP, Garwin JP, Warner EJ. Halothane and children. The first quarter century.Anesth Analgesia 1984;63:838-40.
22. Kenna JG, Neuberger J, Mieli-Vergani G, Mowat AP, Williams R. Halothane hepatitis in children. BMJ 1987;294:1209-11.
23. Shiraishi Y, Ikeda K. Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane and isoflurane. J Clin Anaesth 1990;2:381-6.
24. Ray DC, Bomont R, Mizushima A, Kugimaya T, Forbes Howie A, Beckett GJ. Effect of sevoflurane anaesthesia on plasma concentrations of glutathione-S-transferase. Br J Anaesth 1996;77:404-7.
25. Phillips AJ, Brimacombe JR, Simpson DL. Anaesthetic induction with isoflurane or halothane. Anaesthesia 1988;43:927-9.
26. Fisher DM, Robinson S, Brett CM, Perin G, Gregory GA. Comparison of enflurane, halothane and isoflurane for diagnostic and therapeutic procedures in children with malignancies. Anesthesiology 1985;63:647-50.
27. Kamal RS, Khan FA. Caudal analgesia with buprenorphine for post-operative pain relief in children. Paediatr Anaesth 1995;5:101-6.
28. Wolf AR, Hughes D, Wade A, Mather SJ, Prys-Roberts C. Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture. Br J Anaesth 1990;64:430-5.
29. Brockmeyer DM, Kendig JJ. Selective effects of ketamine on amino-acid mediated pathways in neonatal rat spinal cord. Br J Anaesth 1995;74:79-84.
30. Kristensen JG, Hartvig P, Karlsten R, Gordh T, Halldin M. CSF and plasma pharmacokinetics of the NMDA receptor antagonist CPP after intrathecal, extradural and iv administration in anaesthetized pigs. Br J Anaesth 1995;74:193-200.
31. Jamali S, Monin S, Begon C, Dubousset A-M, Ecoffey C. Clonidine in pediatric caudal anesthesia. Anesth Analgesia 1994;78:663-6.
32. Lee JJ, Rubin AP. Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children. Br J Anaesth 1994;72:258-62. [Abstract/Free Full Text]
33. Naguib M, Sharif A, Seraj M, El Gammel M, Dawlatly AA. Ketamine for caudal analgesia in children: comparison with caudal bupivacaine. Br J Anaesth 1991;67:559-64. [Abstract/Free Full Text]
34. Cook B, Grubb DJ, Aldridge LA, Doyle E. Comparison of the effects of adrenaline, clonidine and ketamine on the duration of caudal analgesia produced by bupivacaine in children. Br J Anaesth 1995;75:698-701.
35. Semple D, Findlow D, Aldridge LM, Doyle E. The optimal dose of ketamine for caudal epidural blockade in children. Anaesthesia (in press).