prolonged ventilation (Playfor et al., 2007; Twite et al., 2004). Th e patients frequently develop polytolerance (Playfor et al., 2006). As a result, achieving adequate sedation leve ls can be challenging and the patient may resist mechanical ventilation and require physica l restraint despite receiving high doses of multiple agents. Delirium and emergence phenome na are experienced and complicate the clinical assessment of pain, distress, and septic epi sodes (Playfor et al., 2006). Th ese patients commonly receive supplementation with alterna - tive sedative agents (Playfor et al., 2006; Tobias, 2005; Twite et al., 2004) including a ntihistamines, chloral hydrate (25 \200\223100 mg/kg, 4 \200\2236/24), psychoactive agents (haloperidol, chlorpromazine, and more recently olanzapine (Stoddard et al., 2006)), propof ol infu- sions 1 to 3 mg/kg/h for limited periods (with the clinicians being aware of propo fol infusion syndrome) and alpha-2 agonists cloni- dine (transdermal, intermittent IV bolus doses 2 \200\2235 mcg/kg three times daily or infusion 0.1 \200\2232 mcg/kg/h) and more re cently dexme- detomidine by IV/subcutaneous (SC) infusion at (0.1 \200\2232 mcg/kg/h with o r without loading dose of 0.5 \200\2231 mcg/kg) (Lin et al., 2011; Phan and Nahata, 2008; T obias, 2007, 2008; Walker et al., 2006). ICU staff may involve an acute pain service early or prior to dis- charge to the standard ward. Th e newer COX-2 inhibiting agents (Anderson, Chapter 43, this volume) available are IV par ecoxib (a prodrug of valdecoxib) and oral valdecoxib in its own right. Oral celecoxib is in capsule form which may be challenging to administer to children. A suspension is stable (D onnelly et al., 2009) but has not been marketed. Th ese agents are used off license in chil dren during or post surgery where bleeding is a concern and reduction or avoidance of opioi d use is desirable, e.g. in patients with respiratory or neurological compro- mise or obstr uctive sleep apnoea. COX-2s are without the platelet inhibition eff ect but still share the NSAIDs \200\231 renal eff ects and are thus used post-stabilization in acute trauma and bu rns. Th ey are employed in skin graft surgery, to reduce opioid requirement par- ticularly when pruritis with burns is prominent, or for bone graft - ing surgery when the clinicians wish to avoid NSAIDs. Regional analgesia Single-shot blocks performed in the ED can be repeated aft er ward admis sion and are employed perioperatively for these patients. Anaesthesiologists can off er cat heter techniques and local anaes- thetic infusions (see Zempsky, Chapter 47, this volume) ( usually performed while anesthetized) for internal fi xation and limb reim- plantation proc edures of the upper (brachial plexus and interscalene techniques) and lower limbs (femoral and fascia iliaca), fractured ribs, fl ail segments, and thoracotomy (intercostal nerve blo cks and paravertebral block/catheter) or for thoracic or abdominal surgery or lower limb fr acture or graft surgery (epidural or caudal catheter/ single shot). Other perioperative sin gle shot nerve blocks employed are for free fl aps and skin harvesting and/or graft ing. Th ese include lateral cutaneous nerve of thigh and transversus abdominis plane blocks and th e aforementioned brachial plexus, femoral and fascia iliaca blocks (Sethna et al., Chapter 46, this volume). Alpha-2 agonists Th ese agents have multiple desirable properties for use in burn or multit rauma patient management (Phan and Nahata, 2008). Th ey are sedative, anxiolytic, reduce pa tient and distress, sympathetic outfl ow, and are adjunctive analgesics (Playfor et al., 20 06). Th ey are eff ective by reducing release of presynaptic catecholamines. Th e mechanism of analgesic eff ect is unclear with central (locus coeru- leus) versus spinal (descending inhibition) versus peripheral eff ects (via substance P) proposed. ICU analgesia-sedation practices Th ese patients are typically on opioids for prolonged per iods. Th e commonly administered agents in ICU for analgesia and seda- tion management are the opioids morphine and fentanyl and the benzodiazepines midazolam and lorazepam (Playfor et al., 2006; Stoddard et al., 2011b; Tobias, 2005; Twite et al., 2004). A consen- sus guid eline has been created in the UK for critically ill children (Playfor et al., 2006). It sug gests: Clonidine causes a degree of bradycardia and hypotension which may be desirable in the poly tolerant agitated patient but can be problematic during septic episodes. Interestingly in t hermally injured rat studies, clonidine \200\231s vasoconstrictive eff ects were sug- geste d to be detrimental by impairing healing (Cassuto et al., 2005b) and benefi cial in terms o f oedema reduction (Cassuto et al., 2005a). Th e bradycardic, hypotensive side eff ect also occurs with dexme- detomidine. Reports state it is well tolerated during sedation of the c ritically ill patient including pediatric cardiac or respiratory ICU patients (off -label u se; Phan and Nahata, 2008; Tobias, 2007). \227\206 Morphine infusions of 10 to 60 mcg/kg/h. \227\206 Fentanyl infusions of 4 to 10 mcg/kg/h. \227\206 Midazolam 2 to 10 mcg/kg/min. Th e doses for sedation are outlined in the \200\230ICU analgesia-sedation practices \200 \231 section. Alpha-2 agonists are also useful premedicants prior to second-phase trauma or burns surgery: single-dose cloni- dine 2 to 5 mcg/kg orally or IV alone or combined with m idazolam 0.5 mcg/kg oral or 0.1 mg/kg IV. Dexmedetomidine 2 mcg/kg has been used via the in tranasal route and compared favorably to oral midazolam 0.5 mg/kg, as premedication prior t o burns reconstruc- tive surgery (Talon et al., 2009). Ketamine is not mentioned in the 2006 UK consensus. It is used in Australian and US ICUs (T wite et al., 2004). In our experience this patient group requires high infusion rates, e.g. greater than 5 to 7 mcg/kg/min or 300 to 400 mcg/kg/h, while a US review reports the use a s sole agent at high sedative doses of 1 to 2 mg/kg/h (Tobias, 2005). We typically co-admin ister ketamine, opioid, and benzodi- azepine infusions in these patients when in ICU for da ys to weeks. SECTION 4 pain in specific populations and diseases 178 physical therapy. Th e long-acting component is weaned when the patient requires less than two rescues a day. Th e drop in dose is usu- ally \200\230convenient \200\231 according to the available tablet size. Usually the morning dose is reduced fi rst as the patient can r equest rescue medi- cation while awake during the day. Th e night dose is maintained to fac ilitate comfort in sleep and weaned and ceased last. Case example: trauma (continued) Th e 14-year-old train-surfer went to the operating room to have an intracranial pressure m onitor placed and the right femoral fracture repaired with an internal fi xation device. In the ICU she was sedated using morphine and midazolam infusions. Aft er 24 h, sedation was stopped and she was extubated. She was neu- rologically normal but complained of severe lef t chest pain (rib fractures) and right thigh pain which was inadequately controlled with in termittent boluses of IV morphine. She was started on a PCA device with IV morphine and req uired this for 5 days. Her daily IV morphine consumption was 80 mg, 95 mg, 60 mg, 50 mg, an d 40 mg respectively and so on day 6 she was converted to oxycodone CR and IR. She was stil l complaining of rib pain and disturbed sleep. She was prescribed OxyContin 20 mg morning and 30mg at night and intermittent oxycodone IR 5 to 10 mg with amitriptyline 25 mg at nig ht. She was discharged home on day 10 on OxyContin 10 mg twice daily, oxycodone, ibuprofe n, and amitriptyline 50 mg at night for review by her gen- eral practitioner. A proscriptive opioid taper is prescribed when pain is minimal and tolerance is present wit h little data to support practices (Fisher, 2010). Previously slow tapers were performed si milar in length to the duration of the opioid treatment. More recent practice is to taper b y 10% to 20% daily, ceasing in 5 to 10 days. When an IV is no longer required, patients are switched to the SC route or enteric administration of either a longer acting formulation ( Anand et al., 2010) or a diff erent opioid at equivalent dosing. Withdrawal symp- toms are ideally scored 8-hourly using the withdrawal assessment tool (WAT)-1 (Franck et al., 2012) or modifi ed Finnegan score (Oschman et al., 2011). Morphine sulfate sustained-release gran - ules or methadone elixir are convenient for enteric tube adminis- tration. Treatment can be guided according to withdrawal score tiers and either non-taper performed if moderate sy mptoms persist or rescue doses of immediate release opioids (or benzodiazepines or alpha-2 agonists) prescribed if symptoms are severe. Fentanyl patches can be used if the enteric route is unavailable. A pilot study reports the use of patches in patients treated with high cumulative doses of IV fentanyl. Th is study (Johnson et al., 2010) inappropriately employed the practice of partly covering a fentanyl patch with Tegaderm . Twelve-microgram patches are now available (but use in non-cancer pa in is still off -license). Case example: burns (continued) Th e ongoing pain of the 2-year-old boy with scald burns was treated with oral acetaminophe n and oral oxycodone. Th e burns were debrided in theater on three occasions including graf t ing under a general anesthetic. He required regular burns dressing changes which were con ducted on the ward in the burns bath and later at the bedside under IV ketamine. Pruritis and neuropathic pain Multitrauma patients experience neuropathic pain mechanistica lly related to their injury (e.g. compression or severance of peripheral nerves). Th ey usu ally experience pruritis secondary to opioids. Th is is managed with antihistamines, optimi zation of non-opioid analgesics and opioid rotation, or small-dose naloxone (1 mcg/ kg). Ch ildren and adult burns patients are frequently distressed by neurogenic pruritis (80 \200 \223100% incidence). Th is is oft en severe, and persists for years aft er healing and succ essful graft ing (Goutos et al., 2009, 2010). Neuropathic-like symptoms in the burn wound ( hot sharp pain) are reported early from day 3 (Gray et al., 2011) and later (mean 4.3 month s) post injury in adults (Schneider et al., 2006). Step-down conversions from IV to oral opioids and tapering Th e oral agent chosen and conve rsion plan in a burnt or multi- trauma patient will depend on the: \227\206 Rate/total dose and duration of treatment with opioids. \227\206 Presence of tolerance. \227\206 Presence of ongoing pain sources. Agents used for pruritis in burns include antihistamines, topi- cal doxepin or amitriptylin e, massage therapy, topical treatments such as local anesthetics, colloidal oatmeal, aloe v era and moistur- izer, cool facewasher-icepack application, transcutaneous electrical nerve stimulation, compression garments, ondansetron and the gabapentinoids: gabapentin/pregabal in (Goutos et al., 2009). Five weeks of biweekly 15 min periburn massage sessions benefi tt ed adolescents with burns with reduced pain, itching, and state anxiety versus controls (Pa rlak Gurol et al., 2010). Small open-label adult series of naltrexone (Jung et al., 2009; L aSalle et al., 2008) and IV lidocaine (Koppert et al., 2004) use have promise. More researc h is required to elucidate whether these agents or possibly clonidine could have benefi cia l roles if used early post injury. \227\206 Degree of background pain. \227\206 Breakthrough pain associated with care (turns, dressing changes, physiotherapy, surgery). \227\206 Prevention of opioid withdrawal syndrome when pain is absent or controlled. \227\206 Routes available (oral versus gastric or jejunal feeding tube). \227\206 Timing of further interventions. When the patient is still experiencing pain but is tolerating oral intake, the parenteral o pioid dose received in the preceding 24 to 48 h is calculated. If greater than 0.5 mg/kg/da y of IV morphine equivalent was received, then approximately 50% to 80% of this is given as long-acting (depending on pain severity) with an immedi- ate-release opioid prescribed as a rescue either as a single dose (usu- ally at one-sixth of the patient \200\231s overall u se) or with a range to allow for fl uctuations, e.g. pre-emptive administration prior to ag gressive Th e underlying mechanism of neurogenic itch and neuro- pathic pain-like symptoms probably has similar origin relating to C fi bre in-growth, sprouting, increased spontaneous and hig h- frequency fi ring with stimuli, cross talk and descending inhibitory CHAPTER 18 pain management in major pediatric trauma and burns 179 dysregulation supported in rat nerve (Radtke et al., 2010) and adult human punch biopsy stu dy (Hamed et al., 2011). Gabapentinoids are consequently used in both neuropathic itch and neuropathic pain management. \227\206 Disrupted circadian rhythm, un-conducive environment (noise, light). Non- pharmacological techniques are important and should be instituted as early as permissible in the unwell patient: A pediatric pilot study of gabapentin use for itch reported doses of 5 mg/kg morning, lunch time, and 5 then 10 mg/kg nightly (Mendham, 2004). Itch reduced aft er 24 h of therapy and antihista- mine use reduced or ceased. A stepwise approach was adopted in two groups of 50 patients (25% children). Itch was relieved better in the polytherapy groups: gabapentin (5 mg/kg (maximum 300 mg) three times a day), cetirizine, cyproheptadine group (95%) versus th e chlorpheniramine, cetirizine, cyproheptadine group (84%) ver- sus monotherapy with gabape ntin (10%) or chlorpheniramine (44%) (Goutos et al., 2010). Another adult trial of 28 days of monotherapy reports all 40 gabapentin-treated patients achieving itch-free status compar ed to only three cetirizine treated (Ahuja et al., 2011). \227\206 Improve sleep hygiene (regular to bed and planned waking times), restrict napping, exercise during day. \227\206 Light therapy: UV exposure, dawn simulation. \227\206 Reduce stimuli: restrict visitors, reduce noise, stop TV/gaming. \227\206 Nutritional: avoid caff eine and heavy evening meal. \227\206 Relaxation training. Pharmacological agents are introduced to restore the sleep wake cycle. Th ey are commenced as early as feasible and include: \227\206 Various benzodiazepines orally (PO)/IV or alternative BDZ receptor agonist (zolpi dem: PO). These reduce sleep latency but negatively affect SWS/REM sleep and have rebound i nsomnia on cessation. Pregabalin (75 \200\223300 mg twice daily) has to date been studied in adults only. Neuropa thic pain scale sharp, hot, and itch scores were impacted as were procedural pain scores (G ray et al., 2011). Statistical signifi cance was achieved although the clinical impact was relatively small. \227\206 Melatonin at doses of 0.5 escalating to 1.5 mg/kg PO. This agent should probably be \201 rst line in these patients as not only is it chronobiotic but it is a free radica l scavenger, an antioxidant, reduces pro-in \202 ammatory cytokines and adhesion molecules and may reduce thermal injury-related lymphocytopenia and oxida- tive damage (Maldonado et al., 2007). In rats at high dose (10 mg/kg), it reduces in \202 ammatory marker elevation and coagula- tion disorder (Bekyarova et al., 2010) and gastric mucosal injury (Bekyarova et al., 2009). Antidepressants are increasingly prescribed in US ICUs (Stoddard et al., 2006, 2011b) and e lsewhere for burn (and multitrauma) patients. Early psychopathology is common and anxiety a nd depres- sion can persist for months (van Baar et al., 2011). Antidepressant drugs are us ed for their antineuropathic, sedative, psychomodula- tory, antianxiety, and antidepressant eff ects (Stoddard et al., 2006). Antidepressant administration for pediatric neuropathic pain is sparsely studied with small sample sizes (see Rastogi and Campbell, Chapter 48, thi s volume). In a placebo-controlled crossover study, parents reported sertraline reduced pos t-traumatic stress symptoms without change in the children \200\231s report (Stoddard et al ., 2011a). A placebo controlled trial in signifi cantly burnt children suggests superiority of fl uoxetine (72% response) versus imipramine (60%) and placebo (55%) (Robert et al., 20 08). Th e same group published a chart review of the same agents (Tcheung et al., 2005) whi ch was criticized for inadequate defi nition of acute stress disorder (Th ombs et al., 2006 ) \227\206 Haloperidol, particularly if delirium is present \200\224 0.1 mg/kg PO or 0.02 mg/kg IV. \227\206 Sedative antihistamines \200\224 promethazine, chlorpromazine, etc. which may as sist with pruritis but are simultaneously detrimen- tal to sleep architecture. \227\206 Clonidine 3 to 5 mcg/kg for sedative and anxiolytic properties. \227\206 Antidepressants with sedative side effects: amitriptyline/nortriptyl- ine 0.5 esc alated to 1.5 to 2 mg/kg PO versus treatment of anxiety or depressive disorder with a morni ng SSRI, e.g. \202 uoxetine 5 to 20 mg. Th e potential of antidepressant drug interactions must be care- fully considered. Interact ions can be both positive (e.g. adjuvant analgesia) and negative (CYP2D6 inhibition, seroto nergic syn- drome, e.g. with co-administration of tramadol). \227\206 Gabapentinoids can be administered at higher evening versus morn- ing doses and w ill assist pain, pruritis, anxiety, and cause sedation. Procedural interventions General anesthesia, the performance of local anesthetic blocks int raoperatively, and postoperative parenteral analgesic techniques are discussed elsewhere in this volume. Sleep disturbance Most hospitalized patients have sleep disturbance which is more prominent in trauma and burns patients. Sleep deprivation results from multiple factors (Jaff e and Patterson, 2004): Procedures are oft en performed in the ward and later in the outpatient environment. During sedation-analgesia for a surgical intervention, opportunity can be taken for additional in terventions such as IV or arterial line re-siting or dressing change, passive phys- ical th erapy, and naso-jejunal feeding tube insertion. \227\206 Physiological eff ects of trauma or burns with stress response, reduced growth ho rmone production, and fl uid retention (exac- erbation of obstructive sleep apnoea). Techniques available to the patient during ward procedures \227\206 Psychological eff ects \200\224 post-traumatic stress symptoms and dis- order, a nxiety and depression, distressing repeated procedures. include the following: Propofol IV for light or deep sedation for ward procedures alone and in combination with op ioids or ketamine. A study of paedi- atric burns dressing changes (n = 32) showed equal eff i cacy of IV propofol-fentanyl (1.2 mg: 1 mcg/kg) and propofol-ketamine (1.2 mg: 1 mg/kg) w ith less restlessness in the propofol-ketamine group (Tosun et al., 2008). \227\206 Presence of prolonged periods of pain or pruritis. \227\206 Treatment interventions such as frequent observation, sedative- analgesic adminis tration that aff ect slow wave sleep (SWS) and rapid eye movement (REM) sleep, pharyngeal m otility, and cause hypoventilation (opioids, benzodiazepines, barbiturates). SECTION 4 pain in specific populations and diseases 180 Ketamine is frequently used as a sole agent for burns dressing changes and burns baths. It can be given via various routes: intra- nasal, oral (0.5 \200\2232 mg/kg for analgesia and 5 \200\2237 mg/kg for seda- tion), and IV (0.5 \200\2232 mg/kg) in titrated boluses. Ketami ne (and its active metabolite norketamine) pharmacokinetics have been studied in pediatric burns patients having general anesthesia. Pharmacokinetic parameters were similar to those in pediatric ED fracture patients (Brunette et al., 2011). Simulation dosing data suggests 10 mg/kg orally followed by infusion of 1 mg/kg/h permits short-duration surgical dressing at 45 min. A large retro- spective review reports protocolized IV ketamine administration ( in conjunction with IV or oral midazolam) by nurse practitioners (Owens et al., 2006). Mean ketamine doses of 147 mg IV were given to children of mean weight 30 kg having 347 bedside procedures. Ten events (2.9%) required respiratory intervention: repositioning (2), oral a irway insertion (1), supplemental oxygen via nasal prongs (1) and bag-mask ventilation (4) with none requiring intubation. Rectal S-ketamine 0.75 mg/kg in combination with midazolam 0.4 mg/kg is reported for 47 outpatient dressing changes in 30 young children with 5% to 15 % burns. Sedation was good to excellent in the majority (Heinrich et al., 2004). pain scores were signifi cantly less in the MMD group (reduced by 30% and 50% respectively; Miller et al., 2010). Virtual reality has been employed in a patient series (aged 9 \200 \22340 years) having debride- ment in the hydrotank (burns bath; Hoff man et al., 2008). Key recommendations \227\206 Pain management in trauma and burns patients should be embedded in a standardized approach to trauma care. \227\206 Opioid use is the mainstay of therapy and where possible opioid- sparing adjuvant agents should be introduced. \227\206 Intranasal fentanyl is a novel administration technique that has effi cacy in the pre-hospital and ED setting for trauma patients. Its use is likely to extend to ward and o utpatient settings for this patient group. \227\206 Local anesthetic agents either topically, by infi ltration, or as a nerve or regi onal block should be employed wherever possible to reduce the need for systemic agents (par ticularly opioids) and their subsequent systemic side eff ects. \227\206 Multimodal analgesia is essential in the eff ective management of pain in moderat e to severe multitrauma or burn patients. Evidence supporting this practice in pediatrics i s sparse. N 2 O alone is a popular inhaled analgesic management option during in and outpatient proce dures (e.g. external fi xateur adjust- ments) or dressing change. It can be used in conjunc tion with timely administration of IV, IN, and oral opioids and non-opioids or midazolam. \227\206 Polypharmacy leads to polytolerance; withdrawal scoring should be a routine asses sment performed in these patients during down-titration of opioids and sedatives. Single-dose benzodiazepine via various routes is useful for proce- dural sedation: midazola m providing amnesia and lorazepam and diazepam used for longer-duration anxiolysis-sedation . \227\206 Ketamine is useful as an analgesic and in anesthetic doses for procedural sedation. Oral analgesic-sedative combinations for dressing changes include acetaminophen with a NSAI D, opioid, and a benzodiazepine or clonidine and/or ketamine. \227\206 Alpha-2 agonists have multiple properties of therapeutic benefi t in this patient group. Th e reported negative eff ects of clonidine in thermally injured rats need to be c larifi ed as off -license use of dexmedetomidine in this pediatric patient population is in creas- ing. Both clonidine and dexmedetomidine off er advantages in sedation of these patie nts, and abstinence syndrome prevention and treatment. Non-pharmacological therapies include relaxation training, hyp- nosis, massage, and various forms of distraction therapy includ- ing music, play (including clown doctors), art, schoo ling, cartoon and favorite video/DVD viewing, hypnosis, massage, pet therapy, interactive v ideogames and virtual reality. \227\206 Scientifi c understanding of the neurobiology of pain and the response to thermal injury at cellular, nerve fi bre and tissue level is progressing. Interactive video games (IVGs) and virtual reality (VR) IVGs have been studied in burns pat ients. Nintendo Wii has been compared with Play station Eye Toy . Th e latter was asso- ciated with higher demands and longer duration of active upper extremity motion indicating potential application in (post-burns) rehabilitation (Parry et al., 2012). Immersive VR inv olving a com- puter-generated virtual environment has been employed for pain- ful physiothe rapy. Th e patient wears head gear to exclude visual and aural input of their medical inter vention (Sharar et al., 2007). In adult and pediatric burn patients, worst pain intensity, pain unpleasantness, and time spent thinking about pain are reduced (Sharar et al., 2007). Multiple use of immersive VR was assessed in children: pain scores were reduced and aff ect improved with patients experiencing fun although there was no diff erence in the maximum r ange of motion achieved (Schmitt et al., 2011). \227\206 Gabapentinoids off er benefi ts in neuropathic pain symptoms and pruritis. A mult imodal approach is likely to be of benefi t in these two conditions over mono-therapy alone . \227\206 Depression and anxiety symptoms are prominent several months to years post multit rauma or burn event. Antidepressant therapy should be considered early along with psycholog y/counseling to simultaneously address insomnia, neuropathic pain, pruritis, anxiety, depre ssion, and post-traumatic and current stress. \227\206 Intervention to improve sleep should be employed as early as fea- sible. More stu dy on the benefi ts of therapy with melatonin is required. For outpatient dressing changes, standard distraction (access to TV, video games, stories, toys, nursing staff soothing, and care giver support) was compared to multimodal distractio n (MMD) involv- ing a device that includes a procedural preparation video ( \200\230Bobby g ot a Burn \200\231) and includes games, \200\230touch and fi nd \200\231 stories with mult isen- sory feedback (visual, auditory, and vibratory). Parent and nursing References Ahuja, R. B., Gupta, R., Gupta, G., and Shrivastava, P. (2011). A comparative an alysis of cetirizine, gabapentin and their combination in the relief of post-burn pruritus. 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