response, as treatment must be fl exible enough to adapt to inter- individual variation and unexpected circumstances or events. Side eff ects, such as PONV (postoperative nausea and vomiting), over- sedation, or depression of respiration should also be anticipated, monitor ed, and managed. Pain aft er surgery can vary in intensity and duration, but is virtu- ally always greatest in the early perioperative period. Pain inten- sity decreases in the succeeding days or wee ks depending not only on the type and extent of surgery but also on less predictable inter- individual factors, but can normally be expected to resolve spontaneously over time. In pra ctical terms this implies that in the fi rst postoperative hours and days analgesia should be given regularly, by the clock, until requirements start to fall. Analgesia can then be g iven \200\230when required \200\231 at times when pain is reported or measured, or pain is anticipated, e.g. prior to mobilization. A number of professional organizations have produ ced detailed and helpful guidelines on the analgesic management of postoperative pain in ch ildren. \200\230Good Practice in Postoperative and Procedural Pain \200\231 from the Assoc iation of Pediatric Anesthetists of Great Britain and Ireland are comprehensive, systematic ally developed, evidence-based guidelines on procedure-specifi c analgesic strat- egies for postoperative pain in neonates and children (Howard et al., 2012 ). \200\230Acute Pain Ma nagement: Scientifi c Evidence \200\231 from the Australian and New Zealand College of Anes thetists (Macintyre et al., 2010 ), and \200\230Practice Guidelines for Acute Pain Managem ent in the Perioperative Setting \200\231 from the American Society of Anesthesiologists al so include advice on the management of post- operative pain in children (American Society o f Anesthesiologists, 2012 ). Th e pediatric anaesthesiologist is responsible for the select ion and initiation of an appropriate perioperative analgesic regimen. In many institutions ongoing care is devolved to a multi- disciplinary postoperative pain management service, bu t all pro- viders of postoperative pain treatment should be familiar with the methods, indi cations, doses, and side eff ects of the most commonly used analgesics and analgesic techni ques. Aims \227\206 Understand basic principles of postoperative analgesia. \227\206 Ability to select an age-appropriate postoperative pain assess- ment tool. \227\206 Understand the pharmacology, advantages and disadvantages of the principal analgesics, and analgesic techniques. \227\206 Ability to describe suitable analgesic regimens for frequently encountered surgical procedures and in special situations. General principles Postoperative pain is predictable, but pain intensity and the response t o analgesia are subject to many diff erent patient-deter- mined variables that are not full y predictable. Th erefore, postopera- tive pain should be anticipated and its intensity ass essed frequently during the postoperative period so that appropriate analgesia can be admin istered promptly, and the response to treatment assessed. Analgesia should be planned accor ding to the expected intensity and duration of pain, but must always be titrated against cl inical Negative e \200 ects of postoperative pain Aside from its unpleasant and distressing quali ties, poorly managed pain has negative physiological, psychological, and behavioral consequ ences. Changes in cardiorespiratory, gastrointestinal, endocrine, and immune function that can be prevented by eff ective SECTION 4 pain in specific populations and diseases 270 analgesia are known to occur (see Acute Pain Management: Scientifi c Evidence (3rd edition) for an up-to-date account; Macintyre et al., 2010 ). Postoperative pain can delay re-mobil ization and recovery from surgery and can lead to undesirable long-term eff ects. re-assessment; thereby establishing a cycle of evaluation and treat- ment that should conti nue throughout the postoperative period (Howard, 1997 ). Th is requires training of health care profession- als in the principles of acute pain assessment and the selection and use o f structured pain measurement tools that are suitable for the developmental age of the chil d and the context in which they are to be used. As postoperative pain management must oft e n continue at home following discharge from hospital, parents and carers may also require g uidance and instruction on the assessment of pain. Pain and injury during infancy and childhood can adversely infl uence pain processing mecha nisms in later life, including the response to subsequent pain and injury many years later (see Walker, Chapter 3, this volume). In addition, a small proportion of children may exper ience persistent postsurgical pain for months or years. Predisposing factors include poorly controlled postoperative pain, extensive or repeated surgery involving nerve damage, and p sy- chological vulnerability (Kehlet et al., 2006 ; Macintyre et al., 2010 ; Macrae, 2008 ) . Poorly managed postoperative pain also contributes to adverse and problematic changes in children \200\231s behavior and sleep pattern, which may be observed for prolonged periods aft er surgery, and cause considerable distress and disruption to family life (Karling et a l., 2007 ; Kotiniemi et al., 1997a ; Power et al., 2012 ). Basic principles of measurement For pain to be measured as accurately as possible, the prin ciples underpinning assessment at diff erent developmental ages and in diff erent settings must be understood. Standardized pain measure- ment tools use various diff erent methods of self-report or obser- vations to quantify pain intensity. Older children are able to use s elf-report scales such as the visual analog scale (VAS) or numer- ical rating scale (NRS) b ut these methods are not accurate in chil- dren who are too young to understand such concep ts and cannot be used in infants and pre-verbal or non-verbal children. In order to overcom e these obstacles a variety of scales have been devised using three basic methods of measur ement: Postoperative pain management services Anaesthesiology-led acute pain management services w ere devel- oped to improve the quality and consistency of care following surgery. Th eir re sponsibilities include: provision of education pro- grammes for staff , provision and maint enance of specialized equip- ment (such as patient-controlled analgesia (PCA) pumps), and o verall supervision of pain management and recognition/manage- ment of side eff ects or comp lications ( Box 27.1 ). 1. Self-report (e.g. using diagrams or pictures). 2. Observations of behavior. 3. Observations of physiological parameters. Multidisciplinary institutional Pain Management Services have been established in many hosp itals to fulfi l this role, several mod- els have been described; they are an essential res ource to ensure the quality and consistency of care (Lloyd-Th omas and Howard, 1994 ; Shapi ro et al., 1991 ; Stomberg et al., 2003 ). Such services have facilitated the introduction of complex and innovative infu- sion techniques for pain management in children including P CA, nurse-controlled analgesia (NCA), and continuous regional local anesthesia (LA), e.g. e pidural and paravertebral blocks. As some of these methods are relatively indirect, and not appro- priate for all ages and al l settings, a pain measurement tool should be scientifi cally \200\230validated \200\231 p rior to its adoption for clinical use. An important consequence of this is that pain measur ement tools should not generally be adapted or changed from their original validated form, as even minor adaptations can change the psycho- metric properties of the tool and alter it s accuracy (Howard et al., 2012 ). Validation of pain assessment and measurement tools and detailed description of tools suitable for diff erent ages and set- tings are covered in mo re detail elsewhere (see Brummelte et al., Chapter 38; Chorney and McMurty, Chapter 37; Lee and Stevens, Chapter 35; von Baeyer, Chapter 36, this volume). Pain assessment and measurement Eff ective pain assessment is central to the prevention and relief of postoperative pain (Finley et al., 2005 ; Howard, 2003 ; Taylor et al., 2008 ; W alter-Nicolet et al., 2010 ). Postoperative pain should be assessed frequently, its intensi ty documented, and appropriate remedial action taken when indicated. Th e outcome and eff e ctive- ness of pain management strategies should then be confi rmed by Children \200\231s self-report of pain is the preferred approach when- ever possible, and i s usually feasible in children older than 5 years (Stinson et al., 2006 ). An observational measure should be used in conjunction with self-report with 3- to 5-year-olds because the evi- dence for the reliability and validity of self-report measures of pain intensity alone in this age group is quite limited, and a number of potential problems and biases have bee n identifi ed when children do not fully understand the scale or the concepts underpinning it (Howard et al., 2012 ; von Baeyer et al., 2009 a). Physiological meas- ures, such as cha nges in cardiovascular or respiratory parameters are unreliable indicators of pain as they are very non-specifi c and therefore prone to error. Th eir use in clinical practice is unp roven and therefore they are not recommended as a sole modality, how- ever physiological me asures are sometimes used in combination with observations of behavior in some \200\230com posite \200\231 pain assess- ment tools (Buttner and Fincke, 2000 ; van Dijk et al., 2001 ) . Box 27.1 Role of postoperative Pain Management Services \227\206 Education and training \227\206 Development and implementation of pain management protocols \227\206 Provision of written information for children, parents, and carers \227\206 Supervision of pain assessment practice \227\206 Oversee safe delivery of appropriate analgesia Measurement tools for postoperative pain A considerable number of acute pain measurement to ols exist, but despite the availability of tools they are not always used consistently or \227\206 Monitoring for side eff ects \227\206 Quality control and audit of outcomes. CHAPTER 27 postoperative pain management 271 Table 27.1 Measures for postoperative pain by age well (Broome et al., 1996 ; Franck and Bruce, 2009 ; Karling et al., 2002 ). An evidence-ba sed guideline \200\230Th e Recognition and Assessment of Acute Pain in Children \200\231 t hat provides an evaluation of many currently available tools and advice on selecting approp riate tools has been recently revised by the UK Royal College of Nursing (RCN, 2009 ). Child \200\231s age a Measure/tool b Newborn-3 years old COMFORT or FLACC 4 years old FPS-R + COMFORT or FLACC Th e suitability of a pain assessment tool depends on the age, cognitive level, language, e thnic/cultural background of the child, the setting for which it is to be used and the tool \200\231s psychometric properties i.e. validity, reliability, etc. (Breau and Burkitt, 200 9 ; Mathew and Mathew, 2003 ; Merkel et al., 2002 ; Stinson et al., 2006 ; von Baeyer, 2006 ; von Baeyer and Spagrud, 2007 ). All such factors should be taken into consideration when making choices about which acute pain measurement tool to use. 5 \200\2237 years old FPS-R 8 years and older VAS or NRS or FPS-R a Assuming normal cognitive development. b See text for explanation of tools and abbreviati ons. Adapted with permission from Howard, R. F. et al., Special Issue: Good Practice in Postoperative and Procedural Pain Management, 2nd Edition, Pediatric Anesthesia , Volume 22 , Issue Supplement s1, pp. 1 \200\22379, Copyright 2012 Blackwell Publishing Ltd, http:/ /onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291460-9592. Self-report scales suitable for postoperative pain include the lin- ear VAS, NRS, and diagr ammatic scales such as the Faces Pain Scale Revised (FPS-R; Hicks et al., 2001 ; von Baeyer et al., 2009 b) and the Wong \200\223Baker Faces scale (Wong and Baker, 1988 ). Observatio nal scales include the Face, Legs, Activity, Cry, Consolability (FLACC) scale and the COMFO RT scale (Merkel et al., 2002 ; van Dijk et al., 2005 ). For children with neurocognitive d efi cits or developmental delay, a small number of special pain measurement tools have been devised. Examples are the Non-communicating Children \200\231s Pain Checklist-Postoperativ e Version (NCCPC-PV) that is valid for 3- to 19-year-olds, and the Pediatric Pain Profi le (PPP) valid for 1 to 18 years (Breau et al., 2002 ; Hunt et al., 2004 ). Th e FLACC scale, one of the most widely used tools in clinical practice, has also been adapted (revised FLAC C) and validated for use with cognitively impaired children (Malviya et al., 2006 ). Th e P ostoperative Pain Measure for Parents has been specially devised and validated for parents to assess their child \200\231s pain (Chambers et al., 1996 ). For post- operative pain ass essment in children of normal cognitive ability, Table 27.1 shows some of the most suitable and widely used tools. requirements fall with time as pain intensity decreases, and the \200\230reverse pain ladd er \200\231 concept is oft en used to provide a simple guide to treatment ( Figure 27.1 ). Local anesthesia combined with two or more systemic analgesics such as paracetamol, non-ste roidal anti- infl ammatory drug (NSAID), and an opioid are oft en used as part of a multimo dal analgesic strategy (see later in chapter). Physical and psychological techniques, inclu ding reassurance, distraction, and hypnosis, have proven eff ectiveness for brief procedura l pain (see Taddio, Chapter 19, this volume). Non-pharmacological tech- niques also have a role as a supplement to analgesic drugs in the perioperative period, by helping to allay fe ar and anxiety during potentially painful care such as blood sampling, placing, changing or removing nasogastic tubes, bladder catheters, chest drains, or sutures and during postoper ative mobilization. Routes of drug administration Th e route of administration of a drug is an important determ i- nant of its eff ectiveness. However, in the postoperative setting the number of routes m ay be limited (e.g. during fasting and nil oral periods), and choice of route is an importa nt issue that requires dis- cussion with children and their families (Seth et al., 2000 ). It is well known that children dislike needles, but children are sometimes Analgesia Analgesics and analgesic techniques are selected according to the expected intens ity and duration of postoperative pain. Analgesic STEP 3 Major Surgery Strong opioid by infusion, PCA, NCA, or Epidural Paracetamol NSAID STEP 2 Intermediate Surgery Oral or moderate potency opioid Paracetamol NSAID Decreasing Pain STEP 1 Minor Surgery Non-opioid e.g. Paracetamol NSAID Figure 27.1 Reverse pain ladder. Adapted with permission from the World Health Organization , original available from < http://www.who.int/cancer/palliative/painladder/en/ >. Time SECTION 4 pain in specific populations and diseases 272 reluctant to take oral medications if they fi nd their taste or con- sistency unpalatable, rectal administration may be unacceptable to some families, and children may, or may not, b e willing or able to use a self-administration technique such as PCA. It is important that children \200\231s views are taken into consideration whenever pos- sible and that their wi shes and those of their families are respected when decisions are made regarding the route and method of pain relief. When available, the oral route is usually preferred above all ot hers for its safety, simplicity, and convenience, although accept- able formulations or com binations of drugs with favorite drinks or food may be necessary for them to be tolerated. In the immediate perioperative period, and sometimes for many days later depend- ing on the type of surgery, the oral route cannot be used and so drugs are most commonly given by the intravenous (IV) route. co-administered with opioids to improve postoperative analgesia and reduce opioid dose but supporting evidence is weak and opti- mum doses are not known (Dahmani et al., 2011 ; Elsha mmaa et al., 2011 ). Similarly, there has been recent interest in the use of pre- operative gabapentin prior to potentially nerve-damaging major surgery; postoperative opioid require ments may be reduced in chil- dren but again few data are available (Rusy et al., 2010 ). L A blocks, such as wound infi ltration and simple nerve blocks such as ilio- inguinal or pen ile dorsal nerve block, are relatively easy to perform and analgesia extends into the early postoperative phase following a single injection, thereby reducing the need for other anal gesics. Th ese techniques, or \200\230single-shot \200\231 caudal epidural block, can also be combined with non-opioid analgesics aft er a range of \200\230inter- mediate \200\231 surgeries at and below the inguinal region, e.g. inguinal hernia repair, orchidopexy or cir cumcision. For guidance on which combinations are eff ective for individual procedures, see evidence- based guidelines (Howard et al., 2012 ; Macintyre et al., 2010 ). An advantage of LA techniques is that they may reduce the need for analgesia during the ear ly postoperative period when the oral route is not available. \200\230Single-shot \200\231 nerve blocks (see \200\230Multimodal analgesia \200\231 section), performed under general anesthesia typically provide analgesia of several hours \200\231 duration, which is oft en suffi cient for resumption of oral intake. Other options when analgesics cannot be given o rally include subcutaneous, sublingual, and buccal routes. Subcutaneous opioid infusions ar e particularly useful when IV access is diffi cult or limited and must be preserved for oth er drugs or treatments such as chemotherapy or parenteral nutrition. In the future, novel t echnologies such as transcutaneous drug administra- tion may become a viable choice in the perioperative period, but at present the available formulations are generally unsuitable. Selection of an appropriate analgesic requires specifi c knowl- edge of its developmental p harmacology; a summary for some of the most important analgesics used for postoperative pai n is given here, for more detailed information see chapters where indicated. Paracetamol and NSAIDs Paracetamol and NSAIDs can be used singly or combined for minor surg ery and at home following day surgery (see Anderson, Chapter 43, this volume, for detailed pharmacology of paraceta- mol and NSAIDs). As part of a multimodal analgesic regimen they a re used throughout the postoperative period to supplement other techniques (see Figure 27.1 ). Multimodal analgesia Since the approach of multimodal analgesia was fi rst suggested (Kehle t, 1997 ), the effi cacy of combinations of analgesics and anal- gesic strategies have been shown in numerous studies of postopera- tive pain in children. However, there have been fe w studies with suffi cient sensitivity to demonstrate the individual contribution of a sing le analgesic. In theory, the use of multiple analgesics that are eff ective on diff erent m echanisms of nociception will increase effi cacy whilst minimizing the dose, and therefore potential for adverse eff ects, of each drug. For example, avoiding side eff ects such as s edation, PONV, or respiratory depression from higher doses of opioid analgesics is clearly an important potential advan- tage. A recent meta-analysis of studies involving the use of NSAIDs has shown that as part of a multimodal technique they can also reduce opioid consump tion and the incidence of PONV (Michelet et al., 2012 ). Adjuvant analgesics such as ketami ne are sometimes Paracetamol (acetaminophen) Paracetamol has been studied extensively in children, its devel op- mental pharmacokinetic characteristics are relatively well under- stood, and it can be used safely in the neonatal period provided dosage guidelines are followed (Anderson and Pa lmer, 2006 ). Paracetamol is available for oral administration in syrup, tablet, and disper sible forms, can be given per rectum (but there is very wide variation in the bioavailabili ty of rectal paracetamol) and an IV preparation of paracetamol is also available. Dosage re gimens depend on the age of the child, the route of administration and the duration of trea tment ( Tables 27.2 and 27.3 ). Clearance in neonates is reduced, and the volume of distrib ution is increased, therefore the dose and dose interval are modifi ed for neonates. Th e m aximum Table 27.2 Paracetamol dosing guide \200\224 oral and rectal administration Age Route Loading dose Maintenance dose Interval Maximum daily dose Duration at maximum dose 28 \200\22332 weeks PCA Oral 20 mg/kg 10 \200\22315 mg/kg 8 \200\22312 h 30 mg/kg 48 h Rectal 20 mg/kg 15 mg/kg 12 h 32 \200\22352 weeks PCA Oral 20 mg/kg 10 \200\22315 mg/kg 6 \200\2238 h 60 mg/kg 48 h Rectal 30 mg/kg 20 mg/kg 8 h >3 months Oral 20 mg/kg 15 mg/kg 4 h 90 mg/kg 48 h Rectal 40 mg/kg 20 mg/kg 6 h PCA = post-conceptional age. CHAPTER 27 postoperative pain management 273 Table 27.4 Dosage of NSAIDs Table 27.3 Paracetamol dosing guide \200\224intravenous administration Weight (kg) Dose Interval Maximum daily dose NSAID Dose Interval Maximum daily dose <5 (term neonate) 7.5 mg/kg 4 \200\2236 h 30 mg/kg Ibuprofen 5 \200\22310 mg/kg 6 \200\2238 h 30 mg/kg 5 \200\22310 10 mg/kg 4 \200\2236 h 40 mg/kg Diclofenac 1 mg/kg 8 h 3 mg/kg 10 \200\22350 15 mg/kg 4 \200\2236 h 60 mg/kg Ketorolac 0.5 mg/kg 6 h 2 mg/kg >50 1 g 4 \200\2236 h 4 g Naproxen 7.5 mg/kg 12 h 15 mg/kg Piroxicam 0.5 mg/kg 24 h 0.5 mg/kg Ketoprofen 1 mg/kg 6 h 4 mg/kg daily dose of paracetamol is limited by the potential for hepatotox- icity which can occur following overdose (single or repeated doses exceeding 150 mg/kg in total). Multiple therap eutic doses may also lead to accumulation and toxicity in children who are malnour- ished o r dehydrated. asthmatic children whenever possible but there is reassuring data regarding the safety of s hort-term use of ibuprofen and diclofenac in asthmatic children (Lesko et al., 2002; Short et al., 2000). Nevertheless, they should be avoided in children with severe acute asthma, a nd are contraindicated in status asthmaticus. NSAIDs NSAIDs are eff ective for the treatment of postoperative pain, used alone or in comb ination as part of a multimodal strategy, as they reduce opioid requirements and the combin ation of NSAIDs and paracetamol produces better analgesia than either drug alone (Michelet et al., 2012 ). A number of diff erent NSAIDs and formula- tions are available and suitable for postoperative use, e.g. ibuprofen tablets and syrup, a sublingual dispersible tablet, diclofenac tablets (dispersible and enteric coated), suppositories, and parenteral for- mul ations ( Table 27.4 ). NSAIDs are widely available and generally considered to be safe; nev ertheless it is important to understand how their mode of action can make them a potentiall y undesirable choice of analgesic in certain situations. \227\206 Studies in animals using high doses of ketorolac found that bone fusion was delay ed: Th is has led to concern that the use of NSAIDs in children may delay bone healing foll owing fracture or bony surgery. Th is has not been supported by human studies and the analg esic benefi ts of short-term NSAID use oft en outweigh the hypothetical risk of delayed bon e healing (Howard et al., 2012 ). Th e risks of side eff ects are oft en considered to outweigh the anal- gesic benefi ts in infants and neonates and so these drugs are rarely prescribed for pain for age less than 3 months. Attempts to reduce the undesirable eff ects of NSAIDs have led to the development o f compounds that specifi cally inhibit COX-2, the COX enzyme responsible for the generation of pain and infl ammation. However, these compounds have been shown to cause cardiovascula r side eff ects in adults and have been little studied, and are little used, for postoperat ive pain in children (Turner and Ford, 2004 ). Th e mechanism of action of NSAIDs is via inhibition of cyclo- oxygenase (COX) activity, th ereby blocking the synthesis of pros- taglandins and thromboxane. Because COX is ubiquitous and responsible for many physiological regulatory activities NSAIDs have the potential to cause adverse eff ects, sometimes at therapeu- tic plasma levels: Opioids Opioids remain the most potent and effi cacious group of systemic analgesics for po stoperative pain. Th ey can be given by many routes and are safe for all ages, provided acc epted dosing regimens are used and appropriate monitoring and education of staff are in pla ce. Morphine is the prototype opioid; diamorphine, hydromorphone, oxycodone, and tramadol, are frequent alternatives to morphine in the postoperative period, and Table 27.5 shows the relative potency to morphine. Th e synthetic family of opioids (fentanyl, sufentanil, alfe ntanil, and remifentanil) have a role aft er major surgery and in \227\206 As NSAIDs reduce platelet aggregation and prolong bleeding time, they are contrai ndicated in children with coagulation disorders or in those who are receiving anticoagulant therapy and relatively con- traindicated when there is a high risk of postoperative bleedi ng. \227\206 NSAIDs can cause gastric irritation and gastrointestinal bleed- ing, and therefor e are relatively contraindicated in children with a history of peptic ulcer disease. Th e r isk of adverse gastrointesti- nal eff ects is low when NSAID use is limited to 1 to 3 days, e.g. in the postoperative period, and may be further reduced by co-pre- scription of proto n pump inhibitors such as omeprazole, or hista- mine (H 2 ) receptor antagonists in patient s at higher risk. NSAIDs can inhibit prostaglandin mediated renal function and this eff ect is greater in the presence of renal disease and dehydration. Table 27.5 Relative potency of opioids Drug Potency relative to morphine Single dose (oral) Continuous infusion (IV) \227\206 Renal toxicity is very low in healthy children, but NSAIDs should not be administ ered concurrently with other agents known to cause nephrotoxicity. Tramadol 0.1 1 \200\2232 mg/kg 100 \200\223400 mcg/ kg/h Codeine a / dihydrocodeine 0.1 \200\2230.12 0.5 \200\2231 mg/kg N/A \227\206 NSAIDs have the potential to exacerbate asthma in a predisposed subset of NSAID-s ensitive asthmatics who show cross-sensitivity with aspirin. It is estimated that 2% of ast hmatic children are sus- ceptible to aspirin induced bronchospasm, and 5% of this sub- grou p are likely to be cross sensitive to other NSAIDs. A history of previous uneventful NSAID exposure should be established in Morphine 1 200 \200\223400 mcg/kg 10 \200\22340 mcg/ kg/h Hydromorphone 5 40 \200\22380 mcg/kg 2 \200\2238 mcg/kg/h a Relative potency of codeine depends on metabolizer status \200\224see chapter text. SECTION 4 pain in specific populations and diseases 274 intensive care practice, and can be used intraoperatively to provide analgesia reduce the s tress response to surgery. Th e so-called mod- erate potency opioids, codeine and dihydroco deine, are sometimes used for short-term treatment of postoperative pain of low intensity o r in non-hospital settings. Codeine is usually not recommended for postoperative pain becau se it is a pro-drug, and the production of the active metabolite morphine is very variable and unpredict- able, and can result in either ineff ective analgesia in poor metab- olizers (Williams et al., 2001 ) or relative overdose and toxicity in ultrarapid metabolizers (Kel ly et al., 2012 ; see also Chau and Koren, Chapter 42, this volume). Th e synthetic opioid pethidine (meperid- ine) is not recommended for children, due to the adverse eff ects of it s main metabolite norpethidine. NCA, have utilized a range of opioids (e.g. morphine, fentanyl, oxy- codone, tramadol) and can provide adequate titration of analgesia with an acceptable level of side eff ects (Mort on and Errera, 2010 ). Some typical doses and infusion rates for PCA and NCA are given in T ables 27.6 and 27.7 . PCA has been extensively used in children as young as 5 years of age who can understand the necessary concepts, and compares favorably with continuous morphine infusion but with the added benefi ts of autonomy and ease of titration for patients. PCA infusion programming va riables are bolus size (mg/kg), continuous infusion rate (mg/kg/h), and bolus lock-out inte rval (min). An important diff erence between PCA in young children and PCA in adults, is th at it is not unusual to run a small background infusion for young patients. Th is is regard ed as improving analgesia without compro- mising safety, provided there is adequate monitor ing for sedation and depression of respiration (Morton and Errera, 2010 ). Opioids can cause a wide range of adverse eff ects but substan- tial clinical experience in their use in children means that they can be given safely for postoperative pain, provided dosage guide- lines and some relatively straightforward management principles are followed . Side eff ects of opioids such as nausea and vomiting, sedation, and depression of respira tion are usually dose related. However, their occurrence is not uniform between diff erent opio- ids or even between patients taking the same drug. Th e incidence and severity of sid e eff ects in an individual patient are infl uenced by both the specifi c opioid, dose, rou te of administration, genetic, and developmental factors (see also Hathway, Chapter 44; Str assels, Chapter 45, this volume). Appropriate monitoring and adverse eff ect management sho uld always be included when potent opioids are prescribed, i.e. frequent monitoring of resp iratory rate and level of sedation, and prophylaxis and treatment of PONV. NCA is an analgesic infusion where a nurse activates the button to provide on-demand analge sia within pre-established guidelines. NCA can provide safe and fl exible analgesia for chi ldren who are too young or unable to use PCA; it has been used safely in large numbers of c hildren (Howard et al., 2010 ; Lloyd-Th omas and Howard, 1994 ). NCA can also been used in the neonatal period but some dosing modifi cations have been recommended (see later section related to neonatal analgesia). Regional analgesia Local anesthetics and techniques LA is popular in the perioperative sett ing because it allows pro- found and specifi c analgesia at the site of surgery, oft en wit hout systemic side eff ects. Th e amide LAs bupivacaine, levobupivacaine, and ropivacaine a re most oft en used for perioperative pain, either as a single dose with a duration of acti on of 2 to 4 h, or by con- tinuous infusion. Th e principal drawback of LA techniques is th e relatively limited duration of action with single-shot intraoperative blocks, and the pot ential for serious side eff ects if recommended doses are exceeded ( Table 27.8 ). Strategi es designed to prolong the action of LA include the use of infusion catheters near peripher al nerves, into the epidural space, or elsewhere. Vasoconstrictors may be added to reduce t he systemic absorption of local anesthetic Intravenous opioid analgesia, PCA, and NCA For moderate to severe postoperative pain, espec ially aft er major surgery, continuous IV analgesia using opioids is usually indicated, wit h the addition of intermittent \200\230extra \200\231 analgesia when required for breakthr ough or incident pain (Howard et al., 2012 ). In recent years, the techniques of PCA and NC A have also become popular, which allow for bolus administration with a lock-out period, wi th or without a background infusion. Some institutions have even introduced the concept of PCA-by-proxy (Anghelescu et al., 2005 ; Howard, 2003 ; Howard et al., 2010 ; Lloyd-Th omas and Howard, 1994 ; Nelson et al., 2010 ). Opioid infusions, including PCA and Table 27.6 Patient-controlled analgesia doses and infusion rates Opioid Loading dose (mcg/kg) Bolus (mcg/kg) Lock-out (min) Background (mcg/kg/h) Morphine 50 \200\223100 10 \200\22320 (max 1mg) 5 \200\22310 0 \200\2234 Fentanyl 0.5 \200\2231.0 0. 25 \200\2230.5 (max 50 mcg.) 5 \200\22310 0 \200\2230.1 Oxycodone 50 \200\223100 10 \200\22320 (max 1mg) 5 \200\22310 0 \200\2234 Table 27.7 Nurse-controlled analgesia doses and infusion rates (not neonates) Opioid Loading dose (mcg/kg) Bolus (mcg/kg) Lock-out (min) Background (mcg/kg/h) Morphine 50 \200\223100 10 \200\22320 (max 1 mg) 20 \200\22330 4 \200\22310 Fentanyl 0.5 \200\2231.0 0. 25 \200\2230.5 (max 50 mcg.) 0 \200\22330 0 \200\2230.1 Oxycodone 50 \200\223100 10 \200\22320 (max 1 mg) 20 \200\22330 0 \200\2234 CHAPTER 27 postoperative pain management 275 Table 27.9 Dose and side e \200 ects of epidural neuraxial analgesics Table 27.8 Suggested maximum dose of bupivacaine, levobupivacaine, and ropivacaine Drug Single dose Infusion Side e \200 ects Single bolus injection Maximum dosage Clonidine 1 \200\2232 mcg/kg 0.08 \200\2230.2 mcg/kg/h Sedation; dose related hypotension and bradycardia (5 mcg/ kg); delayed respiratory depress ion and bradycardia in neonates Neonates 2 mg/kg Children 2.5 mg/kg Continuous postoperative infusion Maximum infusion rate Neonates 0.2 mg/kg/h Morphine 15 \200\22350 mcg/kg 0.2 \200\2230.4 mcg/kg/h Nausea and vomiting; urinary retention; pruritis; delayed respiratory depression Children 0.4 mg/kg/h Fentanyl 0.5 \200\2231 mcg/kg 0.3 \200\2230.8 mcg/kg/h Nausea and vomiting and to prolong their eff ects, and neuraxial analgesics may be been co-administered with th e LA to prolong the eff ect of central nerve blocks (Walker and Yaksh, 2012 ). Tramadol 0.5 \200\2232 mg/kg Nausea and vomiting LA techniques include: Clonidine is an 2-adrenergic agonist and has sedative, anxiolytic, and analgesic propert ies that can be given orally, transdermally, intravenously, or epidurally. It has an establ ished role as a neuraxial analgesic in pediatric practice as clonidine via the intrathecal or caudal/epidural route has a greater eff ect than the same dose intra- venously (Akin et al., 2010 ; Disma et al., 2011 ). Sensitivity to side eff ects of clonidine (apnoea, oxygen desaturation, and bradycardia) is greater in neonates, and cardiovascular and sedative sid e eff ects have been reported following doses of 5 mcg/kg caudal clonidine in children (Sch nabel et al., 2011 ). Epidural clonidine 0.08 to 0.12 mcg/kg/h produces dose-dependent anal gesia when added to LA infusion (De Negri et al., 2001 ), and higher doses of clonidine alo ne (0.2 mcg/kg/h preceded by bolus of 2 mcg/kg) provide analgesia at rest following abdomin al surgery (Klamt et al., 2003 ). Wound infi ltration (oft en performed intraoperatively by the surgeon). Peripheral nerve blocks, e.g. penile dorsal nerve block, ilio-in- guinal-iliohypogastric ne rve block. Field block such as the transversus abdominis plane (TAP) block. Plexus blocks, e.g. axillary brachial plexus block. Central neuraxial blocks such as caudal epidural block, lumbar or thoracic epidural block, and intrathecal spinal block. Ultrasound guidance for regional blocks has become popular as it potentially allows greater accuracy in placement of LA and there- fore improved safety and eff ectiveness (Ivani and Mossetti, 2010 ; Tsui and Suresh, 2010 ). Special situations Day surgery Most surgery in children is done on a day-stay basis. Day su r- gery has social advantages for children and their families, and for health care provider s there are signifi cant economic benefi ts. A long-recognized disadvantage is that potenti ally large numbers of children suff er unnecessary pain and other symptoms at home aft er d ay surgery that can last for several weeks (Kotiniemi et al., 1997 b; Power et al., 2012 ; Wolf, 1999 ). Ensuring that eff ective pain management continues at home aft er day surgery is an important priority. Initiatives designed to improve the quality of care aft er day s urgery include better information for parents about the use of analgesics and non-pharmacol ogical pain management strategies, training in pain assessment, \200\230take home packs \200\231 of medication and rapid access telephone or online support systems. Th e quality o f analgesia at home and the incidence and management of symptoms should always be closely m onitored and audited. Continuous lumbar and thoracic epidural blocks are complex techniques whose potential compl ications include epidural infec- tion or haematoma that could lead to signifi cant permanen t neu- rological defi cit. Th e safety of these techniques is likely to depend on many fact ors including training standards and technical pro- fi ciency, the use of screening tests f or coagulopathy and eff ective aseptic technique, and the monitoring and management of neu- rological signs and symptoms. Recent audits of large numbers of continuous epidural blocks have found that the overall risk of per- manent neurological harm in children is less than 1:10 000 (Ecoff ey et al., 2010 ; Llewellyn and Moriarty, 2007 ; Walker and Yaksh, 2012 ), a fi gure that is broadly similar to the risk of serious complications following continuou s opioid infusions (Howard et al., 2010 ; Morton and Errera, 2010 ). Neuraxial and adjuvant analgesics Drugs that produce a specifi c spinally mediated analgesi c eff ect following epidural or intrathecal administration are referred to as neuraxial ana lgesic drugs. Clonidine, ketamine, and opioids have been used for neuraxial analgesia (see Table 27.9 for typical doses and side eff ects). In combination with LA neuraxial analgesic s can increase the duration of analgesia but the use of some neuraxial analgesics has decli ned in recent years; due to side eff ects in the case of opioids, and because of potential neurotoxicity for ketamine (Engelman and Marsala, 2012 ; Schnabel et al., 2011 ;Walker and Yaksh, 2012 ; Walker et al., 2010 ). Neonates Neonates are a particularly vulnerable group who are also suscep- tible to higher rates of serious complications due to surgery and medications, including analgesics. For ex ample, severe complica- tions following pediatric regional analgesic techniques are rare, b ut the incidence is higher in neonates and infants: 0.4% versus 0.1% for all regional block s or 1.1% versus 0.49% for epidural SECTION 4 pain in specific populations and diseases 276