1 Astrid Lindgrens Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 2 University of Glasgow, Royal Hospital for Sick Children, Glasgow, Scotland, UK
* Corresponding author. E-mail: nsmorton{at}tiscali.co.uk
Keywords: analgesia, paediatric ; analgesics ; pain, acute ; pain, postoperative
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Introduction |
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Neonatal pain perception |
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Successful postoperative pain management in infants and children |
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Prevention of pain whenever possible, using multi-modal analgesia, has been shown to work well for nearly all cases and can be adapted for day cases, major cases, the critically ill child, or the very young. Many acute pain services use techniques of concurrent or co-analgesia based on four classes of analgesics, namely local anaesthetics, opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen (paracetamol).61 72 74 97 98 117 119 135 In particular, a local/regional analgesic technique should be used in all cases unless there is a specific reason not to and the opioid-sparing effects of local anaesthetics, NSAIDs, and acetaminophen (paracetamol) are useful. Indeed, for many day-case procedures, opioids may be omitted because combinations of the other three classes provide good pain control in most cases.88 125 Regional anaesthesia is nearly always conducted in anaesthetized children, but some high risk neonates have lower perioperative morbidity after inguinal surgery when awake spinal anaesthesia is used.91 161
An individualized pain management plan72 can be made for each child based on a cycle of assessment and documentation of the child's pain using appropriate tools and self-reporting, with interventions linked to the assessments.30 60 63 A safety net is needed for rapid control of breakthrough pain, to monitor the efficacy of analgesia, to identify and treat adverse effects, and to ensure equipment is functioning correctly.116
In paediatric hospitals or other centres with significant numbers of paediatric surgical interventions, the establishment of a dedicated paediatric pain service is the standard of care. Where this is not possible, adult pain services often manage children with specific paediatric medical and nursing advice and expertise. In other settings substantial improvement is possible by the establishment of clinical routines and protocols for the assessment and treatment of paediatric postoperative pain. A network of nurses with a special interest in paediatric pain management can form the basis for continuous education. A well-structured protocol for postoperative analgesia with clear instructions for parents is essential following paediatric day-case surgery.118 124 125 165
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Local and regional anaesthesia |
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Safety aspects of paediatric regional anaesthesia
A large prospective 1-yr survey of more than 24 000 paediatric regional anaesthetic blocks found an overall incidence of complications of 0.9 in 1000 blocks, with no complications of peripheral techniques.65 Complications were transient and half were judged to have been caused by the use of inappropriate equipment. The commonest problems with paediatric regional anaesthesia are technical: either failure to establish a block or failure of maintenance of the block. Infection, pressure area problems, peripheral nerve injury, local anaesthetic toxicity, and serious adverse effects of opioids are much rarer.42 A large 5-yr prospective audit of 10 000 paediatric epidural catheter techniques is currently taking place in the UK to try to establish the relative risk of these problems in modern practice.
Some simple local anaesthetic techniques for postoperative analgesia
Local anaesthetic gel topically applied to the site of circumcision, and instilled onto or infiltrated into small open wounds are simple, safe, and effective techniques.7 56 135 Wound perfusion can also be particularly useful for iliac crest bone graft donor sites (used for alveolar bone grafting in some techniques of cleft palate repair).119 Dressing perfusion by applying dilute local anaesthetic onto a foam layer applied to skin graft donor sites is also simple, very effective and safe provided the maximum dosage limits are strictly adhered to. These sites can otherwise be extremely distressing to the child for a period up to 48 h.119
Recent developments in regional analgesia
Descriptions of the technical aspects of regional anaesthesia and management of the child with regional block are readily available.35 41 119 121 124 130 Pharmacokinetics of local anaesthetics in infants and children have been comprehensively reviewed recently.107
Spread of epidural dye
Radiological assessment of contrast injected through epidural catheters in babies (1.84.5 kg) after major surgery found that both the quality and extent of spread were different for every baby. Filling defects and skipped segments were common. Spread was more extensive after 1 ml kg1 compared with 0.5 ml kg1 (mean 11.5 [3.03] vs 9.3 [3.68] segments, P=0.014) (but not twice as great) with fewer skipped segments and greater density of dye.158
Confirming the tip position of catheters threaded from the sacral hiatus
The technique of threading catheters from the sacral hiatus to position the tip at thoracic or lumbar level24 reported success rates of 8596%, particularly in small children. A retrospective review of radiographs in babies younger than 6 months of age156 found that only 58 catheter tips were considered optimal (67%); 10 were too high (12%); and 17 were coiled at the lumbosacral level (20%). Some units use radiological screening routinely but for many others this is not feasible. An alternative approach using electrocardiography has been described.153 A specially devised catheter enables display of the electrocardiograph (ECG) signal from the tip and this is compared with the ECG from a surface electrode positioned at the target segmental level. When the ECG traces are identical, the tip of the catheter is at the target level. In a descriptive study of 20 children aged 036 months, the authors were able to position all the tips to within two vertebral spaces of the target levels (either T4, T7, or T10). In contrast to their previous method of using stimulating epidural catheters and evaluating muscle contractions,154 the technique can be used after administration of neuromuscular blocking agents or epidural local anaesthetics. However, neither of the two techniques described by Tsui153 154 will exclude a catheter lying at the appropriate segmental level but in the subarachnoid space or intravascularly.
Ultrasonography-guided regional anaesthetic techniques
Ultrasonography allows real-time visualization of anatomical structures, guides the blocking procedure itself, and shows the spread of the local anaesthetic solution injected. A more rapid onset of block using less local anaesthetic solution is particularly attractive for paediatrics where most blocks are sited in anaesthetized patients. Ultrasound guidance can also be helpful for caudal and epidural blocks in infants and children as the sacrum and vertebrae are not fully ossified.33 103 Ultrasound-guided techniques have been described for infraclavicular brachial plexus blockade,86 and lumbar plexus block in children.103
Surface mapping of peripheral nerves with a nerve stimulator
Nerve mapping using a nerve stimulator is helpful for teaching peripheral nerve and plexus blocks in the upper and lower limbs, and in patients where the surface landmarks are obscure or distorted.27
Use of continuous peripheral nerve blocks
Continuous catheter techniques are becoming popular in children for femoral, brachial plexus, fascia iliaca, lumbar plexus, and sciatic blockade.37 39 40 82 Disposable infusion devices can be used as an alternative to standard infusion equipment.38
Choice of local anaesthetic solution
A large safety study has established safe-dosing guidelines for racemic bupivacaine in children (Table 1) and this has greatly reduced the incidence of systemic toxicity.19 169 Racemic bupivacaine is gradually being replaced by ropivacaine or levobupivacaine. This change is driven by the reduced potential for systemic toxicity and the lower risk of unwanted motor blockade. There are now sufficient paediatric data to recommend either of the new agents.25 31 44 78 79 80 81 82 95 120 133 151 170 Bosenberg has reported non-toxic plasma concentrations of ropivacaine following a dose of up to 3 mg kg1 for ilioinguinal blockade,23 28 but 3.5 mg kg1 for fascia iliaca compartment blockade has been reported to cause potentially toxic plasma concentrations, namely 45 µg ml1.129 Thus, the reduced risk of systemic toxicity should not persuade anaesthetists to exceed the previous dosing guidelines for racemic bupivacaine. For continuous epidural levobupivacaine, the use of a 0.0625% solution appears optimal for lower abdominal or urological surgery.95 For single injection caudal blockade, ropivacaine and levobupivacaine provide similar postoperative analgesia compared to racemic bupivacaine with slightly less early postoperative motor blockade,36 49 80 and with no discernible differences between ropivacaine and levobupivacaine.49 79 80 The esterase systems in tissues, plasma, and red blood cells are mature in early life, and ester local anaesthetics such as amethocaine (tetracaine) and 2-chloroprocaine are particularly applicable in neonates.18 93 99 160
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Neuraxial blockade for paediatric cardiac surgery
The potential benefits and risks of regional anaesthesia for paediatric cardiac surgery have recently been investigated and reviewed.21 57 75 76 Single doses of intrathecal opioids with or without local anaesthetic, or continuous spinal anaesthesia using a microcatheter technique appear particularly promising for open heart surgery, while epidural or paravertebral techniques seem to offer benefit for closed procedures. The main concern is that of local bleeding at the site of subarachnoid or epidural puncture in a heparinized child.21
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Systemic analgesia |
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Other methods of opioid delivery
Oral, sublingual, transdermal, intranasal, and rectal routes have been described and have a role in specific cases.73 101
Other opioids
Tramadol, oxycodone, hydromorphone, and buprenorphine may have applicability as alternatives to morphine in the postoperative period.59 101 171 Pethidine (meperidine) is not recommended in children because of the adverse effects of its main metabolite, norpethidine. Fentanyl, sufentanil, alfentanil, and remifentanil may have a role after major surgery and in intensive care practice. Remifentanil is very titratable and has a context-insensitive half time with extremely rapid recovery because of esterase clearance, but transition to the postoperative phase is difficult to manage and may be complicated by acute tolerance. It may have a particular role in intraoperative stress control and in neonatal anaesthesia.45 46 102 132 138 Sufentanil and fentanyl have long context sensitive half times but give a smoother transition to maintenance analgesia. Alfentanil has a rapid onset, is titratable, and is relatively context insensitive after 90 min, with a relatively smooth transition in the postoperative phase. The potent opioids may be best delivered by target-controlled infusion devices and paediatric pharmacokinetic programmes have now been developed (Tables 3 and 4).
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs are important in the treatment and prevention of mild or moderate pain in children.89 NSAIDs are highly effective in combination with a local or regional nerve block, particularly in day-case surgery.89 118 NSAIDs are often used in combination with opioids and the opioid sparing effect of NSAIDs is 3040%, as reported for adults.10 123 This produces a reduction in opioid-related adverse effects, especially ileus, bladder spasms and skeletal muscle spasms, and facilitates more rapid weaning from opioid infusions or PCA.72 74 119 128 159 NSAIDs in combination with acetaminophen (paracetamol) produce better analgesia than either alone.10 71 89 Novel formulations of NSAIDs as eye drops have found application after strabismus correction or laser surgery to the eye.122 Pharmacokinetic studies of NSAIDs have revealed a higher than expected dose requirement if scaled by body weight from adult doses.54 137 NSAIDs should be avoided in infants less than 6 months of age,89 115 children with aspirin or NSAID allergy, those with dehydration or hypovolaemia, children with renal or hepatic failure, or those with coagulation disorders, peptic ulcer disease or where there is a significant risk of haemorrhage. Concurrent administration of NSAIDs with anticoagulants, steroids, and nephrotoxic agents is not recommended. The most commonly reported adverse effects of NSAIDs are bleeding, followed by gastrointestinal, skin, central nervous system, pulmonary, hepatic, and renal toxic effects. Other serious side-effects have been reported, including oedema, bone marrow suppression, and StevensJohnson syndrome.89 134 136
NSAIDs and tonsillectomy
Two recent meta-analyses have considered the role of NSAIDs in post-tonsillectomy haemorrhage.92 113 One included studies of aspirin, which is not recommended in children.92 The other showed a small increased risk of re-operation for bleeding in patients receiving NSAIDs.113 However, the authors discuss why clear recommendations cannot be drawn from the evidence as the patients receiving NSAIDs benefited from good pain control and reduced PONV.113 Thus, for every 100 patients, two more will require re-operation if they receive a NSAID than if they do not, but 11 will not have PONV who otherwise would.113 These meta-analyses did not include studies of COX-2 inhibitors.
NSAIDs and asthma
Provocation of bronchospasm by NSAIDs is thought to be a result of a relative excess of leukotriene production. Aspirin sensitivity is present in about 2% of children with asthma and around 5% of these patients are cross-sensitive to other NSAIDs.89 Caution is required in those with severe eczema or multiple allergies and in those with nasal polyps. It is important to check for past exposure to NSAIDs as many asthmatic children take these agents with no adverse effects.134 A recent study found no change in lung function in a group of known asthmatic children given a single dose of diclofenac under controlled conditions.145
NSAIDs and bone healing
Concerns have been raised by animal studies showing impaired bone healing in the presence of NSAIDs.89 For most orthopaedic surgery in children, the benefits of short-term perioperative use of NSAIDs outweigh the risks but limitation of use is recommended in fusion operations, limb lengthening procedures, and where bone healing has previously been difficult.89
COX-2 inhibitors in paediatrics
Several COX-2 inhibitors have recently been evaluated in paediatrics, although the situation has been complicated by the withdrawal of rofecoxib from worldwide markets.155 Some early studies used too low a dose,131 and pharmacokinetic studies are now informing dosing schedules and intervals in children.58 146 147 The studies show equal efficacy to other analgesic interventions with non-selective NSAIDs or acetaminophen (paracetamol) and a morphine-sparing effect, but trials have not been large enough to confirm reduced adverse effects such as bleeding.84 144 157
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Acetaminophen (paracetamol) |
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The analgesic potency of acetaminophen is relatively low and its actions are dose-related; a ceiling effect is seen with no further analgesia or antipyresis despite an increase in dose. On its own, it can be used to treat or prevent most mild and some moderate pain. In combination with either NSAIDs or weak opioids, such as codeine, it can be used to treat or prevent most moderate pain.10 112 A morphine-sparing effect has been demonstrated with higher doses in day-cases.10 90
Acetaminophen is rapidly absorbed from the small bowel, and oral formulations in syrup, tablet or dispersible forms are widely available and used in paediatric practice. Suppository formulations vary somewhat in their composition and bioavailability, with lipophilic formulations having higher bioavailability. Absorption from the rectum is slow and incomplete, except in neonates.14 The novel i.v. formulation pro-paracetamol is cleaved by plasma esterases to produce half the mass of acetaminophen. Recently, mannitol solubilized paracetamol (PerfalganTM) has become available for i.v. use. Interestingly, the higher effect site concentrations achieved in the brain after i.v. administration may result in higher analgesic potency. Although the site of action of acetaminophen is central, dosing is often based on a putative therapeutic plasma concentration of 1020 mg ml1. It is important to realize that the time to peak analgesia even after i.v. administration is between 1 and 2 h. The timeconcentration profile of acetaminophen in cerebrospinal fluid lags behind that in plasma, with an equilibration half-time of around 45 min. Very few studies have tried to relate the concentration of acetaminophen in CSF or plasma to measurements of analgesia, particularly in children. There is evidence that a plasma concentration of 11 µg ml1 or more is associated with lower pain scores. In a computer simulation, a plasma concentration of 25 µg ml1 was predicted to result in good pain control in up to 60% of children undergoing tonsillectomy.811 14 15 Dosing regimens for acetaminophen have been revised in the last few years on the basis of age, route of administration, loading dose, maintenance dose, and duration of therapy to ensure a reasonable balance between efficacy and safety. In younger infants, sick children, and the pre-term neonate, considerable downward dose adjustments are needed (Tables 5 and 6).
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Conclusions |
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Footnotes |
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References |
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