Eur J Anaesthesiol 2015; 32:289–297

REVIEW

Regional anaesthesia in neonates, infants and children An educational review Martin Jo¨hr Prophylactic analgesia with local anaesthesia is widely used in children and has a good safety record. Performing regional blocks in anaesthetised children is a safe and generally accepted practice. When compared with adults, lower concentrations of local anaesthetics are sufficient in children; the onset of a block occurs more rapidly but the duration is usually shorter. Local anaesthetics have a greater volume of distribution, a lower clearance and a higher free (non-proteinbound) fraction. The recommended maximum dose has to be calculated for every individual. Peripheral blocks provide analgesia restricted to the site of surgery, and some of them have a very long duration of action. Abdominal wall blocks, such as transverse abdominis plane or ilio-inguinal nerve

block, should be performed with the aid of ultrasound. Caudal anaesthesia is the single most important technique. Ropivacaine 0.2% or levobupivacaine 0.125 to 0.175% at roughly 1 ml kg 1 is adequate for most indications. Clonidine and morphine can be used to prolong the duration of analgesia. Ultrasound is not essential for performing caudal blocks, but it may be helpful in case of anomalies suspected at palpation and for teaching purposes. The use of paediatric epidural catheters will probably decline in the future because of the potential complications.

Published online 16 February 2015

Introduction Current position of paediatric regional anaesthesia

Regional anaesthesia is mainly used to provide postoperative analgesia. Prophylactic analgesia with local anaesthetics is an attractive concept, especially in paediatric practice, because the evaluation of pain can be very challenging in young children. In contrast to opioids, local anaesthetics can be administered safely, and in recent guidelines regional anaesthesia is accepted as the cornerstone of post-operative pain relief in the paediatric patient.1 Surprisingly, in children, there are only limited data to show that regional anaesthesia really improves analgesia compared with systemic medication; this is true for inguinal hernia repair, urological surgery, cleft lip repair and ophthalmological surgery.2 Regional blocks are usually performed in anaesthetised children. This is an accepted practice provided the clinician selects and performs the technique carefully and is appropriately skilled.3–5 Although regional anaesthesia has a good safety record overall,5–8 the global experience with paediatric regional anaesthesia is still quite low;

even the most commonly performed procedure, caudal block, represents only 2.5% of all central neuraxial blocks performed.9 Determining the risk–benefit ratio is difficult for techniques that are relatively rarely performed.

Developmental pharmacology Lower concentrations of local anaesthetics that are used in adults are clinically effective in children; the onset of a block occurs more rapidly but the duration is shorter. However, with the exception of caudal anaesthesia, no scientific data exist on the best dose and concentration for specific regional blocks in different age groups. Pharmacokinetics

In infants, local anaesthetics have a greater volume of distribution,10,11 a lower clearance,12 and a higher free non-protein-bound fraction.10 The larger volume of distribution counteracts the increased potential for toxicity caused by the larger free non-protein-bound

From the Section of Paediatric Anaesthesia, Department of Anaesthesia, Kantonsspital, Luzern, Switzerland Correspondence to Dr Martin Jo¨hr, Department of Anaesthesia, Kantonsspital, CH-6000 Luzern 16, Switzerland Tel: +41 41 205 4908; fax: +41 41 370 5427; e-mail: [email protected] 0265-0215 ß 2015 Copyright European Society of Anaesthesiology

DOI:10.1097/EJA.0000000000000239

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

290 Jo¨hr

fraction. This means that the amount used for single-shot procedures in terms of ml kg 1 can be the same in children as for adults. For a continuous infusion the situation in the developing organism is much more complex;13 the maturation of the metabolism has to be taken into account. CYP1A2 which metabolises ropivacaine is immature before 4 to 7 years of age, whereas CYP3A4/7, which metabolises levobupivacaine, has full enzymatic capacity by the age of 1 year. Unfortunately, no well designed study compares the two local anaesthetic molecules. Pharmacodynamics

In neonates and infants, nerve fibres are thinner, they have less myelin and the nodes of Ranvier are located closer to each other. Therefore, a smaller sleeve of local anaesthetic solution is sufficient to block three nodes of Ranvier or more, a prerequisite for the blockade of saltatory conduction. Nerve fibres are more susceptible to the effects of local anaesthetics, and a shift of the dose–response curve to the left has been shown in young rabbits.14 Systemic toxicity

In animal experiments, young individuals are more resistant to the toxic effects of local anaesthetics than older ones.15 But, when using a whole-organ preparation, the effect of bupivacaine on cardiac contractility was even greater in neonatal rabbits than in adult rabbits.16 Toxicity occurs when high plasma levels are reached following the absorption of an excessive dose of local anaesthetic, or when the drug is inadvertently injected into the vascular space.

levobupivacaine similar limits should probably be followed; some experts consider that with ropivacaine slightly higher doses may be used safely. But for a continuous infusion, the immature metabolism of the very young has to be taken into account (Table 1).

Peripheral blocks Peripheral blocks provide analgesia restricted to the site of surgery and some of them have a very long duration of action. Their safety record is good. However, peripheral blocks are not without risk: needle trauma, compression/ ischaemia and neurotoxicity are mechanisms that can lead to neurological complications. The recommended doses are based mainly on experts’ opinion and not on evidence. When the injections are made with ultrasound guidance, a very low volume can be seen to provide adequate spread (Table 2). Topical anaesthesia

EMLA cream (which contains prilocaine 2.5% and lidocaine 2.5%) is almost universally used for skin analgesia before venous puncture in awake children. It works best with an application time of 60 to 90 min and should be removed 15 min before the intended procedure in order to allow regression of the prilocaine-mediated vasoconstriction. At higher doses, prilocaine can cause methaemoglobinaemia. Because of the reduced activity of methaemoglobin reductase in neonates and young infants, there is an increased risk of methemoglobinemia,18 even after moderate doses of prilocaine.19 However, the use of EMLA cream is safe, even in this age group, as long as the dose is restricted to 1 to 2 g.20,21 Wound infiltration

The maximum recommended dose must be calculated for every individual patient. Although this dose should not lead to clinically relevant toxicity, provided that the patient is healthy and the anaesthesiologist adheres to all the tenets of good practice, signs of toxicity may still occur in sick patients, or following unintended intravascular injection.17 In paediatric regional anaesthesia, it is a rule of safety to draw up only the exact amount of drug needed.

Wound infiltration is employed chiefly to provide postoperative analgesia but it can only be expected to produce reliable analgesia if the surgery could have been performed under infiltration anaesthesia alone, in an awake child - for example superficial skin surgery. When used after laparotomy22 or for port-site infiltration after laparoscopic surgery,23,24 it may be only a partial remedy for post-operative discomfort.

It is generally accepted that the amount of bupivacaine should be limited to 2.5 mg kg 1 for single injections and to 0.25 mg kg 1 h 1 for continuous infusions. With

Anaesthesiologists in most cases use a skin wheal before performing a major conduction block in awake children. In addition, infiltration is extensively used by

Table 1

Maximum recommended doses for various local anaesthetics

Bupivacaine Levobupivacaine Ropivacaine Lidocaine Prilocaine

Single injection (mg kgS1)

Continuous infusion (mg kgS1 hS1)

2.5 2.5 3 to 4 7 7 to 10

0.25 0.25 0.4 2 (?) Not suitable

Comments

0.2 mg kg

1

h

1

in the first 6 months of life

Not recommended in infants and young children because of an increased risk of methaemoglobinaemia

These doses are in large part not evidence based and represent experts’ opinion.

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Paediatric regional anaesthesia

Table 2

Dosage of local anaesthetics for peripheral nerve block S1

Type of the block

Dosage (ml kg

Rectus sheath block TAP-block Ilio-inguinal nerve block Penile block Brachial plexus block Femoral nerve block Sciatic nerve block

)

0.1 to 0.2 0.2 to 0.5 (maximum 20 ml) 0.1 to 0.3 2  0.1 0.3 to 0.75 0.3 to 0.75 0.3 to 0.75

These doses are mainly based on experts’ opinion and not on evidence. When the injections are made under ultrasound guidance, a sufficient spread can often be seen with a very low volume. TAP-block, transversus abdominis plane block.

paediatricians, surgeons and emergency physicians for the repair of skin lacerations or minor superficial surgery. With appropriate psychological guidance, infiltration can be performed with minimal suffering of the child, provided certain rules are followed (Table 3).25–29 Wound infiltration is widely used in clinical medicine in adults as well as in children; nevertheless, it is rarely taught in a systematic manner in medical schools. Tonsillar bed infiltration

Initially it was thought that tonsillar bed infiltration was very desirable because it offered the theoretical advantage of pre-emptive analgesia. However, local infiltration of the tonsillar bed has no demonstrable preemptive effect30 and has only a small impact on post-operative pain.31 Infiltration of the tonsillar bed can produce dramatic complications,32,33 although the use of adrenaline containing local anaesthetic solutions reduces blood loss.34 Therefore, the management of post-tonsillectomy pain still relies mainly on systemic medication, opioids and non-opioid analgesics, as well as corticosteroids. Abdominal wall blocks

There is growing consensus that abdominal wall blocks should be performed with the aid of ultrasound, because otherwise imprecise administration of the local anaesthetic and even intra-peritoneal injections commonly occur. A rectus sheath block consists of an injection between the rectus muscle and the posterior rectus sheath. Its main indication is analgesia after umbilical hernia repair or, depending on the site of incision, after open pyloromyotomy. It provides more reliable and longer analgesia than surgical wound infiltration,35 and the absorption kinetic of the local anaesthetic seems to be quite slow.36 The Table 3

291

ideal volume of injection has not yet been defined, but 0.2 ml kg 1 on each side are often used. A transversus abdominis plane block (TAP-block) consists of an injection into a plane between the internal oblique and transversus abdominis muscle (Fig. 1).37,38 It provides unilateral analgesia of the abdominal wall,39 and is an alternative to central neuraxial blocks, when these techniques are not possible, for example, in spinal dysraphism or other anomalies of the spinal canal.40 In addition, the TAP-block technique seems to be useful for analgesia after bone harvesting at the iliac crest.41 Whereas a mid-axillary injection covers the segments T10 to L1, higher segments can be reached with a sub-costal TAP-block.42 The clinical duration of the block and the best volume of injection have not yet been defined in children, but, higher doses seem to improve the duration of analgesia.43 Bilateral TAP-blocks need careful observation of the total local anaesthetic dose because rapid absorption and high plasma levels have been reported in adults.44 Realistically, with a long-acting local anaesthetic and a volume of 0.3 ml kg 1, a duration of 5 to 10 h can be expected. TAP-block is a safe technique, provided the dose is correctly calculated and an intra-peritoneal injection is avoided.45 An ilio-inguinal nerve block provides post-operative pain relief after inguinal incisions, such as herniotomy or orchidopexy. It may not prevent the intra-operative perception of noxious stimuli caused by, for example, traction on the peritoneal sac. In addition, in the case of orchidopexy, ilioinguinal nerve block does not cover the scrotal incision, which surprisingly does not seem to contribute to a major extent to post-operative pain. An additional pudendal nerve block could cover this location but in younger children, a caudal block would provide more reliable and more complete analgesia. With ultrasound guided ilio-inguinal block the typical complications of a landmark-based technique46 such as femoral nerve block47 and intestinal puncture48–50 can be avoided. Finally, the ilio-inguinal nerve block scores better than a TAP-block for inguinal hernia repair.51 A volume of 0.1 to 0.3 ml kg 1 is often used; however, in children, the clinical duration as well as the optimal volume is largely unknown. Penile block

Anaesthesia of the dorsal nerve of the penis is considered the standard for analgesia after penile surgery. A variety

The rules for an injection of local anaesthetics with minimal pain, for example, for a skin wheal before performing a conduction block

Factor

Comments

References

Needle size Speed of injection Site of injection Local anaesthetic

Thin needles cause less pain A slow injection is far less painful Infiltration from inside of the wound is less painful compared with an injection through the intact skin Alkalinised lidocaine causes less pain compared with a plain solution

Impact of order

A second injection is perceived more painfully compared with the first one

Palmon et al.25 Scarfone et al.26 Bartfield et al.27 Palmon et al.25 Bartfield et al.28 Bartfield et al.29

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292 Jo¨hr

Fig. 1

Anterior

choice of the needle size and the injected volume differ between the adult and the paediatric surgical patient; but, in other respects, the indication and the techniques are identical so they are not discussed in detail in this review. The ease of diffusion of local anaesthetics in children compared with adults makes it easier to achieve an excellent block.

Posterior

External oblique

Continuous catheter techniques are also used in paediatric patients61,62 but they are mostly restricted to special patient groups with chronic pain.63,64 This may be related to technical difficulties with paediatric catheters that include leakage of local anaesthetic solution along the catheter, and also the fact that complete pain relief often does not lead to a satisfied and comfortable child, and sedative effects of opioids are needed anyway.

Internal oblique

Transversus

Abdominal cavity 3,3

Miscellaneous blocks Transversus abdominis plane block consists of an injection into a plane between the internal oblique and transversus abdominis muscle. The arrow shows the path of the needle.

of techniques are available such as the classical sub-pubic puncture or a sub-cutaneous ring block; the latter provides analgesia of shorter duration,52 but offers more complete intra-operative analgesia than the sub-pubic injection.53 Sub-cutaneous infiltration of the perineal nerves is required for analgesia of the ventral aspect of the penis to allow pain-free awake surgery.54 Sub-pubic penile block, as described by Dalens et al.,55 consists of the injection of local anaesthetic below the superficial fascia – before it becomes Buck’s fascia – into the fat-filled sub-pubic space, wherein the dorsal nerves of the penis run and give off their branches. Penile block is easy to learn.56 The penis is fixed between the thighs with tape, and the needle, a 25-gauge spinal needle, penetrates the skin 0.5 to 1.5 cm lateral to the mid-line and is directed slightly medially (10 to 208) and slightly distally (10 to 208) until a marked ‘give’ is felt as the superficial fascia is crossed and the tip of the needle enters the sub-pubic space. Two paramedian injections of 0.1 ml kg 1 (up to 2  4 ml) bupivacaine 0.5 to 0.75% without adrenaline are given. This provides prolonged pain relief for up to 24 h. The use of ultrasound has been reported to increase the success rate,57 but in the view of the author, it is not a prerequisite for this block. Subpubic penile block is virtually free of complications.58 It has been suggested that the intrinsic vasoconstriction of ropivacaine could cause penile ischaemia59; however, ropivacaine has been extensively used for this indication in some countries,60 and in any case, similar cases have also been reported with plain bupivacaine. Extremity blocks

Brachial plexus blocks, as well as sciatic and femoral nerve blocks, are widely used in clinical practice. The

A large variety of peripheral nerve blocks are feasible and their use is mainly dependent on the experience of the practitioner. An infra-orbital nerve block can be used for analgesia after cleft lip repair.65,66 In skilled hands, an infra-orbital nerve block can also be used for the repair of upper lip lacerations under deep sedation. For this indication, the author prefers to approach the site of exit of the infraorbital nerve from within the mouth. In contrast, for analgesia after cleft lip surgery the percutaneous approach is usually preferred. A supra-zygomatic maxillary nerve block using a volume of 0.15 ml kg 1 ropivacaine 0.2% has been described for analgesia after cleft palate repair.67 The needle is inserted at the upper edge of the zygomatic arch until contact with the greater wing of the sphenoid is felt; then the needle is redirected in a 208 forward and 108 downward direction into the pterygopalatine fossa. Real-time ultrasound allows the spread of the local anaesthetic to be followed.68 The clinical anatomy has been recently reviewed,69 but no large case series of this technique have yet been reported.

Central neuraxial blocks Anatomical and physiological properties

The dura and the spinal cord reach lower levels in the spinal canal in infants (spinal cord L3 at birth, L1-L2 at 1 year; dura S4 at birth, S2 at 1 year) than in children and adults. The loose epidural fat enhances a more even spread of local anaesthetics, up to the thoracic region. It is widely believed that central blocks in awake infants and young children have limited haemodynamic effects. However, studies measuring cerebral blood flow (by transcranial Doppler) have reported a decrease in blood flow after both spinal and caudal block.70,71 In the context of combined general and regional anaesthesia, hypotension can be observed, although this is not widely reflected in the literature.72

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Paediatric regional anaesthesia

Caudal epidural anaesthesia

Caudal anaesthesia is the single most important regional anaesthesia technique in children. Compared with neuraxial techniques in adults, it can be easily learned.73 The puncture is usually performed with the child in a lateral position, the upper hip flexed at 908, the lower one at 458. The sacral hiatus is identified by palpation.74 The dural sac shifts significantly cephalad when the hips and the spine are in a flexed position.75 Alternatively, in the fully awake neonate, according to the author’s opinion, a caudal block can be performed best with the baby in the prone position. Different types of cannulae are currently in use. Normal hypodermic needles have a long tradition, but some authorities argue that this practice should be abandoned because of the risk of spreading epidermal cells into the spinal canal.76 This has been shown to be a problem in the case of lumbar puncture,77 but no such reports have been published yet after epidural injections. With modern needles, the amount of tissue coring seems to be identical among the different types of needles.78 Specially designed caudal needles with a short bevel and a stylet are available and perhaps reduce the risk of vascular puncture.79 Plastic intravenous cannulae or lumbar puncture needles are also used. The use of short intravenous cannulae has two advantages: first, if coring of some skin occurs, it is irrelevant because it remains in the stylet; second, easy catheterisation is a good sign that the catheter is indeed in the spinal canal. The choice of the needle size depends on the clinician’s preference; larger needles, such as 23 G, give a more clear sensation of the tissues, but the thinner the needle, the less the trauma to the tissues. In the author’s opinion, the needle used should not be larger than 25 G. Ultrasound is not essential for performing a caudal block. On the contrary, it may make a simple procedure more complex and more prone to infection, but it can help in cases of suspected anomalies at palpation and also for teaching purposes. In addition, it has given new insight into the mechanism of caudal anaesthesia. It seems that there is an inverse relationship between age, weight, and height and the number of segments covered by a caudal injection of 1.5 ml kg 1 of ropivacaine 0.2%.80 The injected volume has a surprisingly small impact on the anatomical spread 81 and the anatomical spread is much smaller compared with the clinical spread (Fig. 2).82 A dose of roughly 1 ml kg 1 ropivacaine 0.2% or levobupivacaine 0.125 to 0.175% is adequate for most indications. The volume is usually restricted to 25 ml. Caudal injections using local anaesthetics are not recommended for abdominal incisions in children weighing more than 25 kg. The volume needed for a clinically functioning block depends also on the surgical site, and many practitioners still follow the recommendations given by Armitage83 (Table 4).

293

Fig. 2

Cranial

Caudal

T12

L1

L2 Local anaesthetic

Spinal cord

Caudal block in a 3.5-kg neonate. Ultrasound picture taken immediately after injection. Typically the anatomical spread goes up to a spinal level around T12; the clinical spread for analgesia is much higher.

Additives to local anaesthetics are widely used. Adrenaline (5 mg ml 1) allows the detection of intra-vascular needle placement 84 and should be used, in the author’s opinion, at least for the test dose. In preschool children, the intra-vascular injection of adrenaline is recognised not only by the tachycardia, but also by an impressive T-wave elevation (Fig. 3).85 On the contrary, some practitioners prefer to inject plain solutions because the addition of adrenaline to the local anaesthetic offers an additional source of error. Clonidine prolongs the duration of analgesia by around 4 h,86 but it should be avoided in young infants, as post-operative apnoea can occur.87–90 Morphine provides long-lasting analgesia91 but side-effects, such as nausea, urinary retention, pruritus and respiratory depression, are common,92 and the role of caudal opioids has recently been questioned.93 Importantly, the more lipophilic opioids, such as fentanyl,94 sufentanil,95 pethidine,96 diamorphine,97 or tramadol98 cause side-effects, but do not prolong the duration of analgesia in a clinically relevant way. Ketamine prolongs analgesia,99 but its use should be discouraged, because of potential neurotoxicity100; magnesium,101 dexamethasone102 and dexmedetomidine103 are not yet ready for clinical use. Epidural catheters

Epidural catheters in children are well reported.104 The incidence of permanent damage is probably close to 1 : 10 000, that of severe complications 1 : 1000, and pressure sores occur in 1 : 300. Reports of severe unexplained complications raise concern105 and consequently the value of epidural catheters is fervently discussed, especially for neonates and infants.106 The likelihood is that the use of paediatric epidural catheters will decline in the near future.107

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294 Jo¨hr

Dosage of local anaesthetics (ropivacaine 0.2% or bupivacaine/levobupivacaine 0.125 to 0.175%) for caudal anaesthesia

Table 4

Site of incision Penile or anal surgery Lower extremity Abdominal incision

Dosage (ml kgS1) 0.5 to 0.75 1.0 1.0 to 1.25

experts, including the author, still prefer air but try to avoid its injection. However, the use of thoracic epidural puncture should be restricted to cases of severe illness and extensive thoraco-abdominal surgery, as relevant complications have been reported.119–121 It should be performed only by very experienced operators. Spinal anaesthesia

It is technically easy to insert a catheter via the sacral hiatus. The proximity of the anal region raises concerns about the risk of bacterial contamination,108 and special precautions have to be taken. In larger series, no severe infections have been reported,109 and the method seems to be safe. However, an increased incidence of colonisation of caudal catheters with Gram-negative bacteria has been described.108,110 Also, most of the reported septic111–113 and technical114 complications in connection with paediatric epidural anaesthesia have occurred with catheter techniques and not with single-shot caudal injections. The feasibility of inserting caudal catheters up to a high thoracic level (caudo-thoracic anaesthesia) was mentioned by Paolo Busoni, then described by Bo¨senberg et al.115 and was subsequently confirmed by others.116 However, this technique is only reliably successful when large-bore catheters115 or catheters with a stylet116 are used, and mal-positioning can occur.117 Recent animal data suggest that manipulations with large-bore catheters in the epidural space can cause detectable damage to the spinal cord.118 Therefore, the author of this review is convinced that this technique should be abandoned or only used in a few selected patients. A thoracic epidural puncture allows more precise catheter placement for thoracic or upper-abdominal incisions. Loss of resistance to 0.9% normal saline is almost universally recommended for the identification of the epidural space and there is consensus that none at all or only minimal air should be injected. Nevertheless, some Fig. 3

Since the late 1980s, spinal anaesthesia has been used as a sole anaesthetic, especially in the group of high-risk expremature babies.122 In babies below 5 kg, a dose of 1 mg kg 1 plain bupivacaine 0.5% is usually recommended.123 But, even in skilled hands, spinal anaesthesia seems to have a measurable failure rate,124 and the duration of analgesia is short. Compared with spinal anaesthesia, awake caudal anaesthesia has a slower onset of action, the blockade is less dense and potentially toxic doses of local anaesthetics, 3 mg kg 1 bupivacaine 0.25% or 4 to 5 mg kg 1 ropivacaine 0.375%, are needed. Spinal anaesthesia seems a good theoretical choice for avoiding the potential risk of neurotoxicity of general anaesthesia agents; however, the author of this review is convinced that awake regional anaesthesia should only be used in very selected cases, and that the combination of light general anaesthesia and a regional block is currently the best technique for inguinal hernia repair in these high-risk patients.

Systemic administration of local anaesthetics The beneficial systemic effects of local anaesthetics are frequently discussed in the anaesthetic community. In adults, the use of intravenous lidocaine leads to less pain and faster recovery; an observation that has been supported by several meta-analyses.125,126 Surprisingly, up to now, no comparable experiences in paediatric patients have been published. But it seems unlikely that these positive effects would not be observable in a paediatric population.

Conclusion Regional anaesthesia plays a major role in post-operative pain relief in children, and the classical techniques, such as caudal anaesthesia, wound infiltration and penile block, have an excellent safety record.

(a)

1 mV

(b)

Acknowledgements relating to this article Assistance with the review article: the author wishes to thank Prof. Thomas M Berger (Kantonsspital Luzern, Luzern, Switzerland) for his help in editing the manuscript. Financial support and sponsorship: none.

1 mV

Accidental intra-vascular injection of bupivacaine 0.25% with adrenaline 5 mg ml 1 during attempted caudal anaesthesia in a 2.2-kg neonate observed by the author. ECG tracing at baseline (a) and 15 s after the injection of approximately 0.2 ml kg 1 (b).

Conflicts of interest: none.

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Regional anaesthesia in neonates, infants and children: an educational review.

Prophylactic analgesia with local anaesthesia is widely used in children and has a good safety record. Performing regional blocks in anaesthetised chi...
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