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 blocks (Walker and Yaksh, 2012 ). Similarly, the incidence of seri- ous adverse events duri ng NCA morphine analgesia, at 2.5%, was almost ten times higher in neonates (<1 month of ag e) compared with 0.27% in those older than 1 month (Howard et al., 2010 ). In addition, the re may be long-term consequences to the developing nervous system as injury, pain, and anal gesia have been associated with long-term changes in sensory processing systems in labora- tory surgery models and in children following neonatal surgery (Fitzgerald and Walker, 2009 ; Peters et al., 2005 ; Schmelzle-Lubiecki et al., 2007 ; Walker et al., 2009 ). Drugs suc h as general anesthetics and some analgesics with N-methyl-D-aspartate antagonist and/or -aminobutyric acid agonist activity are known to increase neuro- nal apoptosis (spontaneou s neuronal cell death) in the developing brain in rodents and primates (Stratmann, 2011 ). Clearly, immatu- rity of organ systems renders them vulnerable to dysregulation and even pe rmanent damage necessitating modifi cation of analgesic drug choice and dosage regimens tog ether with increased vigilance for adverse eff ects by staff with specialist training and s kills. Strassels, Chapter 45, this volume). Opioids are indicated postop- eratively and are safe i n neonates, provided dosage guidelines are followed with individual titration against respo nse. Th e risk of res- piratory depression is higher in neonates receiving postoperative NC A, particularly those with intercurrent illness or prematurity (Howard et al., 2010 ; Morto n and Errera, 2010 ). Adequate train- ing of staff and monitoring for side eff ects is esse ntial, and in some centers may warrant nursing in high-dependency or intensive care setting s. NCA regimens for neonates frequently utilize bolus-only administration without backgroun d infusions (Howard, 2010 ; Howard et al., 2010 ). Local anesthesia LA techniques are an appealing option for the immediate perioper- ative pe riod as the need for general anesthesia and potent systemic analgesics is reduced. Neverthe less, the toxicity of LAs is also greater in neonates and so maximum recommended doses are lower, and must not be exceeded (Berde, 1993 ). Bupivacaine is highly protein- bound to 1-acid glycoprotein and albumin. Th e concentration and affi nity of 1-acid glycoprotein for bupivacaine is reduced in neonates, thus increasing the proportion of free unbound dru g, but during epidural infusion techniques reduced hepatic clearance of amide LA is the mor e important factor causing accumulation of bupivacaine than reduced protein binding capacit y, particularly as protein levels tend to increase in response to surgery (Howard et al., 2 012 ; see Table 27.9 for suggested maximum doses). Analgesic doses must be modifi ed in the neonatal period as rapid and profound changes in b ody composition and organ function occur in the fi rst few weeks of life. Changes in body w ater, fat dis- tribution and composition, and plasma protein binding capacity alter the vol ume of drug distribution and other pharmacokinetic variables in neonates. Immaturity of hep atic metabolizing systems and slower renal elimination prolong the elimination time of many drugs such that doses and dose intervals must be modifi ed. Larger inter-individual variat ions in the response to analgesics and their adverse eff ects add further unpredictability (Walker and Howard, 2004 ; see also Chau and Koren, Chapter 42, this volume). Case example: tonsillectomy pain Adam, age 5, weight 20 kg has recurrent tonsillitis and is sched- uled for adeno-tonsillect omy. Th e hospital he attends has an anesthesia pre-assessment clinic, runs a program of pr e-ad- mission visits to the hospital for children and their parents, and has an acute pain management service. Paracetamol Th e pharmacokinetics of paracetamol in neonates has been rela- tively well stu died (Allegaert et al., 2011 ; see also Anderson et al., 2002 , Chapter 43, this volume), w ith recommendations for doses adjusted for age (see Tables 27.3 and 27.4 ). Although parace tamol is used extensively in the neonatal period the potential for overdose due to drug acc umulation with repeated dosing, prescription or administration error are always present. At pre-assessment 2 weeks before surgery Adam \200\231s health is found to be good except f or mild asthma for which he takes salbutamol and beclomethasone by inhaler. Th e pre-assess ment nurse asks if Adam has ever taken NSAIDs such as ibuprofen in the past, and his mother says that she has never given them to him because he has asthma. Th e nurse notes this, an d mentions that it is some- times OK to give NSAIDS to children with asthma. Adam \200\231s fam- ily are given a leafl et explaining the adeno-tonsillectomy surgery that includes dis cussion of postoperative pain and how it will be managed. As pain aft er tonsillectomy can persist for several days following discharge the need for analgesia at home, possibly for a s long as 10 days, is noted. Th e leafl et includes a brief expla- nation of pain assessmen t procedures and an example of a self- report pain scale, using diagrams of faces. NSAIDs Although this group of drugs is used for pharmacological closure of patent ductus ar teriosus in premature neonates they are not gener- ally a suitable choice for postoperative pain until aft er 3 months of age. Prostaglandins, inhibited by NSAIDs, have multiple regu latory roles and are especially important in early development. Increased risk of pulmonary hypertension, changes in cerebral blood fl ow, decreased renal function- ibuprofen has bee n shown to reduce glomerular fi ltration rate in neonates by 20%, defi cient thermoregu- la tion, and disrupted sleep cycle are just some of the increased risks anticipated with the u se of these drugs in the neonatal period. One week prior to surgery Adam and his mother also attend the pre-admission visit where a f urther explanation of pain assess- ment takes place. A nurse instructs Adam in use of the f aces pain self-report scale, and Adam \200\231s mother asks questions about what she will n eed to do for pain at home. Opioids Plasma clearance of opioids is reduced in neonates, and correlates with weight and post-conceptual age (Bouwmeester et al., 2004 ; Kart et al., 1997 ; Lynn et al., 2000 ). Al though the plasma concentra- tion of morphine associated with analgesia is not known, both phar- macokinetic and pharmacodynamic factors contribute to reduced dose requirements in ne onates (see also Hathway, Chapter 44; and On the day of surgery the anaesthesiologist discusses the peri- operative pain management p lan with Adam and his mother during the pre-anesthesia consultation. He explains that durin g the surgery the tonsillar fossa will be infi ltrated with LA, which will be eff ective in the early postoperative period, but the eff ects CHAPTER 27 postoperative pain management 277 Bouwmeester , N. J. , Anderson , B. J. , Tibboel , D. , and Holford , N. H. ( 2004 ). Devel opmental pharmacokinetics of morphine and its metabolites in neonates, infants and young ch ildren . Br J Anaesth , 92 , 208 \200\223217. will wear off aft er 1 or 2 h. Adam will also receive paracetamol (acetaminophen) and an op ioid (fentanyl), during the surgery plus prophylactic medication for PONV. Analgesia will b e given every few hours, and more will be available if needed. Breau , L. , Finley , G. , McGrath , P. , and Camfi eld , C. ( 2002 ). Validation of the No n-communicating Children \200\231s Pain Checklist-Postoperative Version . Anesthesiology , 96 , 528 \200\223535. Adam \200\231s mother is concerned about the potential use of NSAIDs, and the anaesthesiolo gist explains the risks and ben- efi ts of NSAIDS aft er tonsillectomy. Although risks are low, they decide not to use NSAIDs without further discussion. Adam wakes up in the post-an esthesia care unit (PACU), feels disori- entated, fi nds it diffi cult to swallow, and he i s in pain. Th e PACU nurse administers IV morphine analgesia and Adam sleeps for a time, an d then wakes up and is transferred to the ward area for the next few hours. Aft er a while Adam \200\231s throat hurts a lot and it is diffi cult to swallow, and he indicates the pen ultimate face on the faces pain scale. He is given further paracetamol and some oral morphi ne, but also feels nauseous. As he continues to have pain, the nurse calls the anaesthesiol ogist who assesses Adam and discusses analgesic options with Adam \200\231s mother. Th e an aesthesiologist recommends giving a dose of ibuprofen (an NSAID) and Adam \200\231s mother agrees. About 45 min later, Adam seems much better and he is prescribed regular alternating doses of paracetamol and ibuprofen, and additional oral morphine if needed. Breau , L. M. , and Burkitt , C. ( 2009 ). Assessing pain in children with intellectual disabilities . Pain Res Manag , 14 , 116 \200\223120. Broome , M. E. , Richtsmeier , A. , Maikler , V. , and Alexander , M. ( 1996 ). Pediatric p ain practices: A national survey of health professionals . J Pain Symptom Manage , 11 , 312 \200\223320. Buttner , W. and Fincke , W. ( 2000 ). Analysis of behavioral and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young childre n . Paediatr Anaesthe , 10 , 303 \200\223318. Chambers , C. , Reid , G. , McGrath , P. , a nd Finley , G. ( 1996 ). Development and preliminary validation of a postoperative pain mea sure for parents . Pain , 68 , 307 \200\223313. Dahmani , S. , Michelet , D. , Abback , P. S. , Wood , C. , Brasher , C. , Nivoche , Y. , e t al . ( 2011 ). Ketamine for perioperative pain management in children: a meta-analysis of published studies . Paediatr Anaesth , 21 , 636 \200\223652. De Negri , P. , Ivani , G. , Visconti , C. , De Vivo , P. , and Lonnqvist , P. A. ( 2001 ). Th e dose-response relation ship for clonidine added to a postoperative continuous epidural infusion of ropivacaine in children . Anesth Analg , 93 , 71 \200\22376. Disma , N. , Frawley , G. , Mameli , L. , Pistorio , A. , Alberighi , O. D. , Montobbio , G . , et al . ( 2011 ). Eff ect of epidural clonidine on minimum local anesthetic concentrati on (ED50) of levobupivacaine for caudal block in children . Paediatr Anaesth , 21 , 128 \200\223135. Th e next morning Adam is due to be discharged, but his mother is quite concerned about man aging Adam \200\231s pain at home. A nurse explains that for 3 days she should continue to give regu- lar medication (paracetamol and ibuprofen \200\230by the clock \200\231) unless any side eff ects occur, and thereaft er to give analgesia at bed- time and according to p ain assessments. Adam \200\231s mother is given written instructions and a telephone number to call if she needs further advice, and she is told that someone from the hospital will c ontact her the following day. Aft er returning home Adam \200\231s mother speaks to a nurse as planned, she is asked about Adam \200\231s pain and is given advice, reassurance, and a reminder of who to contact if necessary. Adam recovers well and returns to school aft er a further week. Ecoff ey , C. , Lacroix , F. , Giaufre , E. , Orliaguet , G. , and Courreges , P. ( 2010 ). Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospe ctive survey of the French-Language Society of Pediatric Anaesthesiologists (ADARPEF) . Pae diatr Anaesth , 20 , 1061 \200\2231069. Elshammaa , N. , Chidambaran , V. , Housny , W. , Th omas , J. , Zhang , X. , and Michael , R. ( 2011 ). Ketamine as an adjunct to fentanyl improves postoperative analgesia and haste ns discharge in children following tonsillectomy \200\224a prospective, double-blinded, ran domized study . Paediatr Anaesth , 21 , 1009 \200\2231014. Engelman , E. and Marsala , C. ( 2012 ). Bayesian enhanced meta-analysis of post-operative analgesic effi cacy of additives for caudal analgesia in children . Acta Anaesthesiol Scand , 56 , 817 \200\223832. Finley , G. A. , Franck , L. , Grunau , R. , and Von Baeyer , C. L. ( 2005 ). Why children \200\231s pain matters , Seattle, WA : IASP . References Akin , A. , Ocalan , S. , Esmaoglu , A. , and Boyaci , A. 2010 ). Th e eff ects of caudal or intravenous clonidine on postoperative analgesia produced by caudal levobupiva caine in children . Paediatr Anaesth , 20 , 350 \200\223355. Fitzgerald , M. and Walker , S. M. ( 2009 ). Infant pain management: a developmental neurob iological approach . Nat Clin Pract Neurol , 5 , 35 \200\22350. Franck , L. S. , and Bruce , E. ( 2009 ). Putting pain assessment into practice: why is it so painful? Pain Res Manag , 14 , 13 \200\22320. Allegaert , K. , Palmer , G. M. , and Anderson , B. J. ( 2011 ). Th e pharmacokinetics of i ntravenous paracetamol in neonates: size matters most . Arch Dis Child , 96 , 575 \200\223 580. Hicks , C. , Von , B. C. , Spaff ord , P. , Van , K. I. , and Goodenough , B. ( 2001 ). Th e Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement . Pain , 9 3 , 173 \200\223183. American Society of Anesthesiologists. ( 2012 ). Practice guidelines for acute pain managem ent in the perioperative setting: an updated report by the American Society of Anesthesiolo gists Task Force on Acute Pain Management . Anesthesiology , 116 , 248 \200\223273. Howard , R. ( 1997 ). Planning for pain relief . In S. Lindahl (ed.) Clinical anaesthesiolo gy: pediatric anesthesia , Vol. 10, pp. 65 \200\223676. London : Bailliere Tindall , Anderson , B. and Palmer , G. ( 2006 ). Recent developments in the pharmacological manageme nt of pain in children . Curr Opin Anaesthesiol , 19 , 285 \200\223292. Howard , R. ( 2003 ). Current status of pain management in children . JAMA , 290 , 2464 \200\2232469. Howard , R. , Carter , B. , Curry , J. , Jain , A. , Liossi , C. , Morton , N. , et al . ( 2012 ). Good practice in postoperative and procedural pain management: guidelines from the Association of Pediatric Anesthetists . Paediatr Anaesth , Suppl 1, 1 \200\22381. Anderson , B. , Van Lingen , R. , Hansen , T. , Lin , Y. , and Holford , N. ( 2002 ). Aceta minophen developmental pharmacokinetics in premature neonates and infants: a pooled populat ion analysis . Anesthesiology , 96 , 1336 \200\2231345. Howard , R. F. ( 2010 ). Audits of postoperative analgesia: what have we learned Anghelescu , D. L. , Burgoyne , L. L. , Oakes , L. L. , and Wallace , D. A. ( 2005 ). Th e safety of patient-controlled analgesia by proxy in pediatric oncology patients . Anesth Ana lg , 101 , 1623 \200\2231627. and what should we do now? Paediatr Anaesth , 20 , 117 \200\223118. Howard , R. F. , Lloyd-Th omas , A. , Th omas , M. , Williams , D. G. , Saul , R. , Bruce , E. , et al ( 2010 ). Nurse-controlled analgesia (NCA) following major surgery in 10,000 pa tients in a children \200\231s hospital . Paediatr Anaesth , 20 , 126 \200\223134. Berde , C. ( 1993 ). Toxicity of local anesthetics in infants and children . J Pediatr , 122 , S14 \200\22320. SECTION 4 pain in specific populations and diseases 278 Peters , J. , Schouw , R. , Anand , K. , Van Dijk , M. , Duivenvoorden , H. , and Tibboel , D. ( 2005 ). Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain , 114 , 444 \200\223454. Hunt , A. , Goldman , A. , Seers , K. , Crichton , N. , Mastroyannopoulou , K. , Moff at , V. , et al . ( 2004 ). Clinical validation of the pediatric pain profi le . Dev Med Child N eurol , 46 , 9 \200\22318. Power , N. M. , Howard , R. F. , Wade , A. M. , and Franck , L. S. ( 2012 ). Pain and behav ior changes in children following surgery . Arch Dis Child , 97 , 879 \200\223884. Ivani , G. and Mossetti , V. ( 2010 ). Continuous central and perineural infusions for post operative pain control in children . Curr Opin Anaesthesiol , 23 , 637 \200\223642. Royal College of Nursing. ( 2009 ). Clinical practice guidelines. The recognition and asses sment of acute pain in children . London : Royal College of Nursing . Available at: < www.r cn.org.uk/__data/assets/pdf_ fi le/0004/269185/003542.pdf > (accessed 30 June 2012). Karling , M. , Renstr m , M. , and Ljungman , G. ( 2002 ). Acute and postoperative pain in children: a Swedish nationwide survey . Acta Paediatr , 91 , 660 \200\223666. Karling , M. , Stenlund , H. , and Hagglof , B. ( 2007 ). Child behavior aft er Rusy , L. M. , Hainsworth , K. R. , Nelson , T. J. , Czarnecki , M. L. , Tassone , J. C. , Th ometz , J. G. , et al . ( 2010 ). Gabapentin use in pediatric spinal fusion patients: a randomized, double-blind, controlled trial . Anesth Analg , 110 , 1393 \200\2231398. anesthesia: associated risk factors . Acta Paediatr , 96 , 740 \200\223747. Kart , T. , Christrup , L. , and Rasmussen , M. ( 1997 ). Recommended use of morphine in ne onates, infants and children based on a literature review: Part 2 \200\224clinical use . Pa ediatr Anaesth , 7 , 93 \200\223101. Schmelzle-Lubiecki , B. M. , Campbell , K. A. , Howard , R. H. , Franck , L. , and Fitzgera ld , M. ( 2007 ). Long-term consequences of early infant injury and trauma upon somatosenso ry processing . Eur J Pain , 11 , 799 \200\223809. Kehlet , H. ( 1997 ). Multimodal approach to control postoperative pathophysiology and rehabilitation . Br J Anaesth , 78 , 606 \200\223617. Kehlet , H. , Jensen , T. , and Woolf , C. ( 2006 ). Persistent postsurgical pain: risk Schnabel , A. , Poepping , D. M. , Kranke , P. , Zahn , P. K. , and Pogatzki-Zahn , E. M. ( 2011 ). Effi cacy and adverse eff ects of ketamine as an additive for pediatric caudal ane sthesia: a quantitative systematic review of randomized controlled trials . Br J Anaesth , 107 , 601 \200\223611. factors and prevention . Lancet , 367 , 1618 \200\2231625. Kelly , L. E. , Rieder , M. , Van Den Anker , J. , Malkin , B. , Ross , C. , Neely , M. N. , et al . ( 2012 ). More codeine fatalities aft er tonsillectomy in North American children . Pediatrics , 129 (5), e1343 \200\2231347 Schnabel , A. , Poepping , D. M. , Pogatzki-Zahn , E. M. , and Zahn , P. K. ( 2011 ). Effi cacy and safety of clonidine as additive for caudal regional anesthesia: a quantitative sys tematic review of randomized controlled trials . Paediatr Anaesth , 21 , 1219 \200\2231230 . Klamt , J. G. , Garcia , L. V. , Stocche , R. M. , and Meinberg , A. C. ( 2003 ). Epidural infusion of clonidine or clonidine plus ropivacaine for postoperative analgesia in children undergoing major abdominal surgery . J Clin Anesth , 15 , 510 \200\223514. Seth , N. , Llewellyn , N. , and Howard , R. ( 2000 ). Parental opinions regarding the rout e of administration of analgesic medication in children . Paediatr Anaesth , 10 , 537 \200 \223544. Kotiniemi , L. , Ryhanen , P. , and Moilanen , I. ( 1997 a). Behavioral changes in children following day-case surgery: a 4-week follow-up of 551 children . Anesthesia , 52 , 970 \200\223976. Shapiro , B. , Cohen , D. , Covelman , K. , Howe , C. , and Scott , S. ( 1991 ). Experience of an interdisciplinary pediatric pain service . Pediatrics , 88 , 1226 \200\2231232. Kotiniemi , L. , Ryhanen , P. , Valanne , J. , Jokela , R. , Mustonen , A. , and Poukkula , E. ( 1997 b). Postoperative symptoms at home following day-case surgery in children: a mul ticentre survey of 551 children . Anesthesia , 52 , 963 \200\223969. Stinson , J. , Kavanagh , T. , Yamada , J. , Gill , N. , and Stevens , B. ( 2006 ). Systema tic review of the psychometric properties, interpretability and feasibility of self-report pain intensity measures for use in clinical trials in children and adolescents . Pain , 125 , 143 \200\223157. Llewellyn , N. and Moriarty , A. ( 2007 ). Th e national pediatric epidural audit . Paediatr Anaesth , 17 , 520 \200\223533. Lloyd-Th omas , A. and Howard , R. ( 1994 ). A pain service for children . Stomberg , W. M. , Lorentzen , P. , Joelsson , H. K. , Lindquist , H. , and Halamje , H. ( 2003 ). Postoperative pain management on surgical wards-impact of database documentation of anesthesia organized services . Pain Manage Nurs , 4 , 155 \200\223164. Pediatric Anesthesia , 4 , 3 \200\22315. Lynn , A. , Nespeca , M. , Bratton , S. , and Shen , D. ( 2000 ). Intravenous morphine in p ostoperative infants: intermittent bolus dosing versus targeted continuous infusions . Pain , 88 , 89 \200\22395. Stratmann , G. ( 2011 ). Review article: neurotoxicity of anesthetic drugs in the Macintyre , P. E. , Schug , S. A. , Scott , D. A. , Visser , E. J. , and Walker , S. M. ( 2 010 ). APM:SE Working Group of the Australian and New Zealand College of Anesthetists and F aculty of Pain Medicine. Acute pain management: scientifi c evidence (3rd edn). Melbourne : ANZCA and FPM . Available at: < http://www.fpm.anzca.edu.au/resources/books-and-publicatio ns/ publications-1/Acute%20Pain%20-%20fi nal%20version.pdf >. developing brain . Anesth Analg , 113 , 1170 \200\2231179. Taylor , E. M. , Boyer , K. , and Campbell , F. A. ( 2008 ). Pain in hospitalized children: a prospective cross-sectional survey of pain prevalence, intensity, assessment and managem ent in a Canadian pediatric teaching hospital . Pain Res Manag , 13 , 25 \200\22332. Tsui , B. C. , and Suresh , S. ( 2010 ). Ultrasound imaging for regional anesthesia in infa nts, children, and adolescents: a review of current literature and its application in the p ractice of neuraxial blocks . Anesthesiology , 112 , 719 \200\223728. Turner , S. and Ford , V. ( 2004 ). Role of the selective cyclooxygenase 2 (COX-2) inhibitors in children . Arc h Dis Child Educ Pract Ed , 89 , ep46 \200\223ep49. Van Dijk , M. , De Boer , J. B. , Koot , H. M. , Duivenvoorden , H. J. , Passchier , J. , Bouwmeester , N. , et al . ( 2001 ). Th e association between physiological and behavioral pain measures in 0-to 3-year-old infant s aft er major surgery . J Pain Symptom Manage , 22 , 600 \200\223609. Macrae , W. A. ( 2008 ). Chronic post-surgical pain: 10 years on . Br J Anaesth , 101 , 77 \200\22386. Malviya , S. , Voepel-Lewis , T. , Burke , C. , Merkel , S. , and Tait , A. R. ( 2006 ). Th e revised FLACC observational pain tool: improved reliability and validity for pain assess ment in children with cognitive impairment . Paediatr Anaesth , 16 , 258 \200\223265. Mathew , P. J. , and Mathew , J. L. ( 2003 ). Assessment and management of pain in infants . Postgrad Med J , 79 , 438 \200\223443. Merkel , S. M. S. , Voepel-Lewis , T. , and Malviya , S. M. D. ( 2002 ). Pain Assessment in Infants and Young Children: Th e FLACC Scale: a behavioral tool to measure pain in young c hildren . AJN , 102 , 55 \200\22358. Michelet , D. , Andreu-Gallien , J. , Bensalah , T. , Hilly , J. , Wood , C. , Nivoche , Y. , et al . ( 2012 ). A meta-analysis of the use of no nsteroidal antiinfl ammatory drugs for pediatric postoperative pain . Anesth Analg , 114 , 393 \200\223406. Morton , N. and Errera , A. ( 2010 ). APA national audit of pediatric opi oid Van Dijk , M. , Peters , J. , Van Deventer , P. , and Tibboel , D. ( 2005 ). Th e COMFORT B ehavior Scale: a tool for assessing pain and sedation in infants . Am J Nurs , 105 , 33 \200\22336. Von Baeyer , C. and Spagrud , L. ( 2007 ). Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years . Pain , 127 , 140 \200 \223150. Von Baeyer , C. L. ( 2006 ). Children \200\231s self-report of pain intensity: scale select ion, limitations and interpretation . Pain Res Manage , 11 , 157 \200\223162. Von Baeyer , C. L. , Forsyth , S. J. , Stanford , E. A. , Watson , M. , and Chambers , C. T. ( 2009 a). Response biases in preschool children \200\231s ratings of pain in hypothetical situations . Eur J Pain , 13 , 209 \200\223213. infusions . Pediatr Anesth , 20 , 119 \200\223125. Nelson , K. L. , Yaster , M. , Kost-Byerly , S. , and Monitto , C. L. ( 2010 ). A national survey of American Pediatric Anesthesiologists: patient-controlled analgesia and other intr avenous opioid therapies in pediatric acute pain management . Anesth Analg , 110 , 754 \200\223760. CHAPTER 27 postoperative pain management 279 Walker , S. M. , and Yaksh , T. L. ( 2012 ). Review article: neuraxial analgesia in neonate s and infants: a review of clinical and preclinical strategies for the development of safet y and effi cacy data . Anesth Analg , 115 , 638 \200\223662. Walter-Nicolet , E. , Annequi n , D. , Biran , V. , Mitanchez , D. , and Tourniaire , B. ( 2010 ). Pain management in new borns: from prevention to treatment . Paediatr Drugs , 12 , 353 \200\223365. Von Baeyer , C. L. , Spagrud , L. J. , McCormick , J. C. , Choo , E. , Neville , K. , and C onnelly , M. A. ( 2009 b). Th ree new datasets supporting use of the Numerical Rating Scale (NRS-11) for children \200\231s self-reports of pain intensity . Pain , 143 , 223 \200 \223227. Walker , S. and Howard , R. ( 2004 ). Neonatal pain . Pain Reviews , 9 , 69 \200\22379. Wa lker , S. M. , Franck , L. S. , Fitzgerald , M. , Myles , J. , Stocks , J. , and Marlow , N . ( 2009 ). Long-term impact of neonatal intensive care and surgery on somatosensory percep tion in children born extremely preterm . Pain , 141 , 79 \200\22387. Williams , D. G. , Hatch , D. J. , and Howard , R. F. ( 2001 ). Codeine phosphate in pediatric medicine . Br J Anaesthes , 86 , 413 \200\223421. Wolf , A. ( 1999 ). Tears at bedtime: a pitfall of extending pediatric day-case surgery without extending analgesia . Br J Anaesth , 82 , 319 \200\223320. Walker , S. M. , Westin , B. D. , Deumens , R. , Grafe , M. , and Yaksh , T. L. ( 2010 ). E ff ects of intrathecal ketamine in the neonatal rat: evaluation of apoptosis and long-term functional outcome . Anesthesiology , 113 , 147 \200\223159. Wong , D. and Baker , C. ( 1988 ). Pain in children: comparison of assessment scales . Pediatr Nurs , 14 , 9 \200\22317. CHAPTER 28 Pain in palliative care Ross Drake and Ren e McCulloch Summary Pain in palliative care for children is common and is oft en a result of dif- feren t combinations of nociceptive (somatic and/or visceral) and neu- ropathic pain rather than being from a single etiology. Th is pain is best addressed through a collaborative, interdi sciplinary team employing a holistic approach to the child and their family. Medication, pa rticularly opioids, has a central role in management but attempting to relieve pain without addressing the child \200\231s non-physical concerns is likely to lead to frustration. Th e expectation should be for exemplary control of pain bearing in mind some of the syndromes faced can be complex and may require quite sophisticated techniques to be managed appropri - ately including the use of surgical and anesthetic procedures. with non-malignant conditions. Conditions experienced by children are quite diff erent from adults as are the anatomy and physiology of the child and their cognitive responses to pai n and pain therapies. However, even in the absence of evidence, safe and eff ective man- ag ement can be achieved through a sensible, empirical approach centered on good observation a nd evaluation and an understanding of the disease process and therapeutics being used. World Health Organization guidelines Th e WHO has infl uenced the management of pain in chi ldren \200\231s pal- liative care through the publication in 1998 of a simple guideline out lining the rational stepwise approach to the management of can- cer pain in children (WHO, 1998 ). Th e guidelines were eff ective in providing analgesia in this group (Zernikow et a l., 2006 ). Clinically, their use was broadened to include children with non-malignant cond itions although this expansion was never validated; an impor- tant factor as over half of c hildren have a non-malignant condition (Drake et al., 2003 ; Feudtner et al., 2011 ). Introduction Palliative care for children is the active total care of the child \200\231s b ody, mind, and spirit, and also involves giving support to the family. Health providers mus t evaluate and alleviate a child \200\231s physical, psychologi- cal, and social distress ( World Health Organization (WHO), 1998 ) through the prevention and relief of suff ering by early identifi cation and impeccable assessment and treatment of pain (WHO, 1996 ). In 2012 the WHO published a major review of the guidelines (WHO, 2012 ) with the new iterat ion based on the best available evidence and extended to cover persistent pain in children with medical illnesses. Th e analgesic ladder remains at the heart of the guidelines but th e three-step ladder was reduced to two steps by removing the measure for mild to moderate p ain. In eff ect, minor opioids are replaced with a low dose of a major opioid. Th e choice of analgesia is determined through \200\230impeccable assessment \200\231 and the point of entry established by the severity of pain. Two aspects of this statement resonate loudly with health care professionals involved in pa lliative care: the reference to the multi- dimensional nature of assessment and management necessitating a collaborative, interdisciplinary team approach by pediatric trained profess ionals and the elevation of pain to a symptom requiring meticulous attention. Pain is, arguably, the most feared symptom faced by children and their families during thei r palliative journey. Pain has a consist- ently high prevalence (Drake et al., 2003 ; Sirki a et al., 1998 ; Wolfe et al., 2000 ) but the ability to satisfactorily control pain can be quite variable (Sirkia et al., 1998 ; Wolfe et al., 2000 ) and changes over the fi nal wee k of life (Drake et al., 2003 ). Th e ladder is supported by three other \200\230rules \200\231 which remain unchanged to complete a logical framework for prescribing. \227\206 By the clock \200\224encourages the regular scheduling of analgesia to ensure a s teady blood concentration and to reduce the peaks and troughs of intermittent dosing. Th is regular dosing should be supplemented with \200\230as needed \200\231 breakthrough doses for pain that may emerge. A signifi cant key to success involves eff ective communication just as much as choosing th e right intervention. Open, honest dis- cussion of assessment and treatment strategies prov ides the foun- dation of a trusting therapeutic relationship that, in turn, allows for dial og about anxieties and misconceptions that can, if not addressed, hamper appropriate manage ment. \227\206 By the appropriate route \200\224requires the least invasive route of administrat ion to be used; the oral route is preferable in most circumstances. \227\206 By the child \200\224promotes individualized treatment according to the assessed need. Unfortunately, the evidence available to support therapeutic approaches to deal with childr en \200\231s pain during palliative care is sparse. Th is requires clinicians to use eviden ce from studies on acute pain in children and the literature of adult palliative care. Th i s latter source demands cautious extrapolation to children, especially those Th e reliance on opioids for pain management in palliative care is a distinguishing factor. However, there are occasions when chil- dren who could benefi t from opioid therapy are, o r their family are, unwilling to have the child take opioids. Th is is usually based CHAPTER 28 pain in palliative care 281 Challenging pain syndromes in palliative care Episodic pain \200\224breakthrough pain versu s incident pain Episodic pain in palliative care is usually seen in children with advanced cancer and equates to either \200\230breakthrough \200\231 or \200\230incident \200\231 p ain. Th ese are two distinct entities although the terms are oft en used, incorrectly, inte rchangeably. on misconceptions about their use and the perception that opioids mark \200\230the beginni ng of the end \200\231. Th ese fears need to be explored and correct information provided. Unfortunately, reservations can be so powerful that a prescription for an alternative agent may be required even if it has, potentially, inferior effi cacy. Simply, there is little p oint in prescribing the ideal drug if it is clear that the child and/or family will not com ply with its administration. Th is makes the availability of eff ective alternatives (perce ived to be safer) of real practical value.