Amy L. Baxter
Lindsey L. Cohen
Corrie E. Chumpitazi
HIGH-YIELD FACTS
• Untreated pain in children causes short- and long-term consequences.
• Buffering intradermal lidocaine with 1:9 concentration of sodium bicarbonate will reduce pain from chemical irritation.
• Oral sucrose on a pacifier can provide pain relief for small infants during painful procedures.
• In children, the most painful part of fracture management is obtaining radiographs. This can be reduced by early splinting of the fracture site.
• Behavioral techniques for management of pain include relaxation exercises, deep breathing, distraction, and imagery.
Pain is the most common reason a patient presents for health care. It is often undertreated for children in ED settings despite recognition of its importance.1
OLIGOANALGESIA FOR PEDIATRIC PATIENTS
Untreated pain in children causes short- and long-term consequences. For example, pain in infants can have lasting negative effects on neuronal development, pain threshold and sensitivity, coping strategies, emotionality, and pain perceptions.2 Children receive less pain medication than adults for the same emergent complaints. The reasons for this “oligoanalgesia” include persistence of myths that children do not experience or remember pain, fear of using opioids in young patients, and difficulty assessing pediatric pain.3 The effects of untreated pain impact medical outcomes and are remembered even by preverbal children.2 These effects may amplify with age: adolescents may avoid medical treatment, adults may refuse to donate blood, and geriatric patients may refuse flu shots because of the fear of needle pain. Children with a history of negative medical experiences show higher levels of anxiety prior to a venipuncture procedure and are less cooperative during the procedure. Further, high pain during medical visits predicts missed future medical appointments and poor health care follow-up. Older children also suffer sequellae: untreated pain from lumbar puncture (LP) increases pain response with subsequent procedures.4 Immediate and long-term patient health are affected by inappropriate analgesia.
PAIN ASSESSMENT
In the ED, the periodic evaluation of pain using the Wong-Baker Faces Pain Scale has become routine for both staff and patients.5 Although widely used in the United States, this scale suffers from two methodologic flaws: the smiling anchor to the left is rarely appropriate for anyone in the ED, and cultural and concrete thinking biases may limit endorsement of the tearful face (Fig. 13-1). The Faces Pain Scale—Revised is used more widely throughout the world, especially in the empirical literature (Fig. 13-2).6 Other validated options include a vertical, graduated, and colored VAS scale to assess pain.7 This upside-down triangle has the topmost part wide and red representing the worst pain and the bottom part narrow and white representing no pain. The scale has been found to be easier to administer than a standard VAS and avoids the most common problem seen with “face”-based scales, choosing higher numbers because of unhappiness rather than pain.
FIGURE 13-1. Wong-Baker Faces Pain Scale. (Reproduced with permission from Wong D.L. Essentials of Pediatric Nursing, 5th ed. Mosby-Year Book;1997.)
FIGURE 13-2. Faces Pain Scale—Revised. For correct use and translations, visit www.painsourcebook.ca. (Reproduced with permission from Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale–Revised: toward a common metric in pediatric pain measurement. Pain. 2001;93(2):173–183.)
The value of pain assessment has empiric support: routine use of pain assessments improves treatment.8 Incorporating pain assessment increases appropriate pain management in ED settings. Self-reporting pain scales are preferred; however, children under the age of 3 are generally not able to differentiate levels of pain. Preschool children may lack the verbal and cognitive skills to report their pain or discomfort, thus several behavioral scales have been developed. The Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) and Faces, Legs, Activity, Cry, Consolability (FLACC) are two commonly used scales.9,10 The FLACC has been validated in critically ill and cognitively impaired children.
PROCEDURAL PAIN MANAGEMENT
VENIPUNCTURE
The American Academy of Pediatrics recommends pain control for venipuncture “whenever possible,” and numerous modalities are effective even within the time constraints of the ED.11 Topical anesthetics (e.g., prilocaine, lidocaine, tetracaine) stop sodium transmission, raising the action potential threshold so the fast pain impulse cannot be conducted. All local anesthetics contain hydrophilic and hydrophobic ends, the former being repelled by the oil layer of intact skin. Three common anesthetic formulations that overcome the skin barrier are eutectic mixture of local anesthetics (EMLA) (Astra-Zeneca, Wilmington, DE), LMX-4 (Eloquest, Ferndale, MI), and tetracaine (e.g., Ametop Gel, Smith & Nephew Healthcare, Hull, UK; Synera, Galen US, Inc; Endo Pharmaceuticals, Malvern, PA).12
Eutectic mixture of local anesthetics is the first and most studied topical cream: prilocaine 2.5% and lidocaine 2.5%. Evidence supports reduction of pain with intravenous (IV) catheter insertion when applied for a minimum of 45 minutes.3,8,13 EMLA can be left on up to 4 hours with a depth of penetration up to 6 mm. Numbness lasts an hour after removal. EMLA causes vasoconstriction, which theoretically can decrease venipuncture success but this is contrary to study outcomes. Venipuncture success improves the longer EMLA is in place, up to 92% when left on for 2 to 3 hours.14 Methemoglobinemia is a rare side effect more likely in preterm infants lacking the enzyme necessary for its reduction. Current recommendations limit EMLA to infants of at least 37 weeks gestational age. A purpuric rash of presumed toxic origins has been described in 1% to 2%, particularly in atopic patients.
LMX-4 (previously called ELA-Max) places a 4% lidocaine preparation into liposomes for rapid absorption. Effective in 30 minutes, it works as well as EMLA for venipuncture pain.15 Rapid dissipation of the drug results in diminishing anesthesia approximately 40 to 60 minutes after application. LMX-4 improves cannulation success on the first attempt (74% vs. 55%) when compared with placebo, and lowers time of insertion and pain scores.16 LMX-4 does not require a prescription and does not carry the risk of methemoglobinemia. Several products enhance absorption of LMX-4 to make it more rapidly effective, including ultrasound devices and lasers.
Tetracaine gel, formerly known as amethocaine (Ametop Gel, Smith & Nephew Healthcare, Hull, UK), is available alone and compounded with lidocaine. The 4% formulation works in 30 to 45 minutes, and lasts 4 to 6 hours with an efficacy similar to EMLA.17
For venipuncture, tetracaine and lidocaine mixture (7%/7%) is available in a self-contained patch. Synera® (ZARS Pharma, Salt Lake City, UT) in the United States and Rapydan™ (Souderton, PA) in the European Union are designed to look like a child’s bandage and recommended for children aged 3 years and older. The patch contains a heating element that decreases absorption time and causes local vasodilation. This mixture was tested to show good topical anesthesia and pain control when applied for less time than EMLA or placebo.15,18
LIDOCAINE DEVICES AND TECHNIQUES
Iontophoresis uses a low-voltage electrical current to drive the positively charged end of lidocaine through the epidermis. As the current flows to the negative reservoir, lidocaine is carried from the positive side into the skin. The current flow is noxious to some children. Time of application is at a minimum of 10 minutes. In contrast, a simple injection of buffered lidocaine using a small gauge needle prior to venipuncture is rapid and well tolerated.19 Use of this method is inexpensive, depending on bundled hospital charges for the extra supplies.
The J-tip (National Medical Products, Irvine, CA) puts lidocaine under the skin via a jet of compressed carbon dioxide. Studies have found the J-tip less painful for IV cannulation than EMLA cream.20 In addition, this method was found to be most cost-effective compared with other topical agents for IV cannulation.21
COLD SPRAY AND VIBRATION DEVICES
Buzzy® (MMJ Labs, Atlanta, GA), combining cold spray and vibration and placed proximal to the site of cannulation, decreased pain by half compared with cold spray and increased IV success.22 Applying vapocoolant spray (Pain Ease, ethyl chloride, Gebauer, Cleveland, OH) to the penetration site has been used in hospitals for needle sticks but the cold spray may cause veins to shrink making cannulation difficult. Placebo-controlled randomized trials have produced varying results for venipuncture. It may be more effective for children older than 8 years. Cannulation on first attempt was more often successful with the use of vapocoolant spray (85.0%) than with placebo (62.5%) and the number needed to treat to prevent 1 cannulation failure was 5 (95% CI 3–32).23 Figure 13-3 provides an algorithm for balancing optimal pain control with time available.
FIGURE 13-3. Options for venipuncture pain (in order of increasing cost).
LACERATIONS
Open lacerations permit easy drug absorption, rendering the hydrophilic ester issue irrelevant. The first combinations of tetracaine and cocaine mixed with “adrenaline” for vasoconstriction (TAC) were very effective but created logistic difficulties with controlled substances. When lidocaine, epinephrine, and tetracaine (LET or LAT) demonstrated equal efficacy, LET became the standard of care for pediatric wound repair.4
A shred of LET-soaked cotton or LET mixed with methyl-cellulose is placed directly in the wound before irrigation and repair. The solution or gel can be held in place with an occlusive dressing, tape, or bandage. Numbness is present when the tissues blanch, usually after 20 minutes, and anesthesia lasts approximately 21 minutes after removal.24 LET alone gives sufficient pain control for 70% to 90% of pediatric facial lacerations, and can decrease length of stay by 30 minutes compared with traditional lidocaine injection.24,25
In extremities, LET has decreased efficacy (approximately 50%) but has not been shown to cause digital ischemia. Mucous membrane absorption is a theoretic concern, but the primary reason to avoid LET for oral lacerations is loss of vermilion border landmarks because of the blanching effect. EMLA has been used for laceration repair but has decreased numbing effect.26 Hydrocodone/acetaminophen has been shown to be effective in reducing pain in combination with LET in children undergoing laceration repair.
INFILTRATION
Both the tissue disruption from the volume of infiltrate and the acidic pH of lidocaine can cause increased pain when lidocaine with or without epinephrine is used for local anesthesia. In adults, pain is diminished when lidocaine is injected slowly with the smallest gauge needle possible.27 Inject from within the wound, not through the adjacent intact skin. When possible, tapping, jiggling, or vibrating several centimeters proximal to the site of infiltration can distract the nerves and decrease the pain of injection. The chemical irritation from lidocaine itself can be minimized by buffering with sodium bicarbonate in a 9:1 ratio in the same syringe. Premixed syringes typically keep for a week in an unrefrigerated environment. Warming the syringe to body temperature is also more comfortable than injecting refrigerated anesthetic.
Consider regional nerve blockade rather than direct local infiltration where appropriate. For a simple digital laceration, local injection was not found to be superior to a digital block.28 For foot lacerations, facial lacerations, and palmar lacerations, regional nerve blockade can be considered, but with smaller lacerations local infiltration may be less painful.
ABSCESS
Incision and drainage may warrant procedural sedation to adequately mitigate pain. Using a combination of topical anesthetic over intact skin and local infiltration of lidocaine in a circular area prior to incision, pain may theoretically be reduced to an extent where parenteral pain medicine alone or with nitrous oxide would be sufficient. When abscesses are packed with gauze, applying LET to the gauze for 20 minutes prior to removal moistens the retained edges of packing allowing for less painful removal. Placement of LMX-4 also may lead to spontaneous drainage and decrease the necessity for procedural sedation.29
LUMBAR PUNCTURE
Self-reported pharmacologic interventions to reduce pain associated with infant LP are used regularly by less than one-third of pediatric emergency medicine (PEM) faculty and fellows.30 Studies have demonstrated improved success rates when topical anesthetics are applied, further supporting a practical as well as palliative role.31 When placed prior to collection of blood and urine, the rapid efficacy of LMX-4 makes it a feasible option for a septic workup, whereas EMLA requires an hour to achieve efficacy. When the LP needs to be performed emergently, as little as 0.1 mL of oral sucrose on a pacifier (e.g., Sweet-Ease, a 24% sucrose and water solution) provides pain relief during the procedure. Effectiveness of sucrose is most commonly cited for preterm infants and neonates younger than 2 months of age, although it may provide pain relief in 6-month-old infants for less invasive procedures.32
For older children, local anesthetics with or without an anxiolytic may be adequate. When a child is expected to require multiple LPs over the course of illness, as with leukemia, providing deep sedation initially improves subsequent fear and posttraumatic stress surrounding the procedure. Otherwise, providing optimal pain control will help avoid “hyperalgesia” and increased pain response with subsequent LPs.4
EMLA has been demonstrated to decrease the pain of LPs in older children. By approximately 3 months of age, topical anesthetics will not penetrate sufficiently past the epidermis for optimal pain control. Infiltrating a generous amount of buffered lidocaine (approximately 1 mL per 10 kg of body weight up to a maximum of 5 mL) into the predural space provides improved pain relief. Short-acting opioids (e.g., fentanyl) can further improve comfort with the procedure.
STOMATITIS
Stomatitis, most often in pediatric patients, is viral in nature (i.e., coxsackie or herpes viruses) and is self-limited. Oral pain medications, such as ibuprofen 10 mg/kg every 6 hours as needed, and encouragement of adequate fluid intake may suffice. Topical therapies are often trialed, such as a 1:1 mixture of aluminum hydroxide/magnesium hydroxide and diphenhydramine or Carafate to coat the ulcers. The addition of topical viscous lidocaine or benzocaine should be avoided in young children because of the risk for toxicity from mucosal absorption or ingestion. In severe cases, oral opioids for pain control and IV fluids for dehydration may be necessary.
PENILE PROCEDURES
Moderate or deep sedation, particularly with a rapid-acting agent such as nitrous oxide, may be ideal for paraphimosis reduction. Local pain control could be either topical or regional. LMX-4 for 30 minutes was equivalent to EMLA for 45 minutes in the meatal region.33 Care should be taken not to leave either on too long to avoid toxic absorption. A dorsal penile nerve block could be considered and oral or IV opioids prior to the procedure will help.
URETHRAL CATHETERIZATION
For children undergoing urethral catheterization, 2% lidocaine jelly (available in a prefilled syringe Urolet) can be administered and allowed to sit for 1 to 2 minutes prior to catheterization. Although effective at reducing pain in adult males, research in children is limited with equivocal outcomes. Nonetheless, some success has been found in reducing distress among infants who had a lidocaine-enhanced lubricant instilled in the urethra for catheterization.34In addition, suprapubic puncture after application of EMLA was well tolerated and associated with a low pain score independent of patient age.35 The use of nitrous oxide for VCUG catheterization may have limited application in an ED. Trials using intranasal fentanyl have yet to have proven effect in providing pain relief.
FRACTURES AND BURNS
Fracture reduction and burn debridement often require procedural sedation to accomplish, as opioid monotherapy can result in inadequate pain control or respiratory depression after procedure completion. A narcotic as a single agent in initial management is appropriate. The common initial parenteral dose of 0.1 mg/kg of morphine is often inadequate for extremely painful events, and 0.15 mg may be considered as an initial dose for injuries such as severe burns or displaced long bone fractures.36 An initial dose of an oral opioid such as hydrocodone or oxycodone may speed pain relief if an IV has not yet been established. Intranasal fentanyl, which is as effective as IV morphine for pain relief, is more rapid but may increase vomiting.
For fracture management, rapid immobilization improves pain relief. Children report initial x-rays as the most painful part of emergency fracture treatment, thus temporary splinting and administration of analgesia prior to obtaining radiographs is recommended. Subsequently, regional pain control is an option for fracture reduction or burn debridement on extremities. A Bier block is a well-described technique used most commonly for forearm fracture reduction. An IV is placed on the affected side, and plain lidocaine and saline are administered after inflation of a double-blood pressure cuff to 250 mm Hg. Within 5 minutes, the extremity becomes mottled and completely numb, and procedures can be performed without pain. This is an excellent option for children for whom a recent meal precludes sedation. Short-acting anxiolytics, regardless of NPO times, can mitigate the patient’s anxiety of witnessing the procedure.
When compared with ketamine sedation, a hematoma block concurrent with nitrous oxide has been described favorably. Femoral nerve blocks for fracture pain have been described, but require specific training to apply effectively. Procedural sedation is most commonly utilized for definitive fracture reduction treatment.37
ANALGESIC AGENTS
The medications in the class of pure analgesic agents include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). They are commonly used as antipyretics and for treatment of minor extremity pain. Rectal administration required 40 mg/kg as a loading dose of acetaminophen to achieve sufficient analgesic blood levels after surgery. Rectal doses of 20 mg/kg are required for subsequent pain relief. IV acetaminophen has become available in the United States for treatment of pain or fever, with a similar pharmacokinetic profile as 15 mg/kg weight-based dosing via oral and rectal routes.38 IV ibuprofen is being trialed in the United States, primary outcome is fever decrease in most studies.39
Ketorolac, the most commonly utilized parenteral NSAID available in the United States, is effective in prostaglandin-mediated conditions, such as biliary or renal colic, although its use in other painful conditions generally requires addition of a supplemental narcotic. Many pure analgesics are also combined with opioid agents for synergistic effects in oral combination therapies.
Synthetic and naturally occurring narcotic analgesics all produce their effect through stimulation of opioid receptor sites in the central nervous system. Differences in the effects of various agents result from differential binding preferences for these receptor sites. Opioid analgesics create dose-dependent pain relief with mild sedative effects. Cardiovascular and respiratory depression may be seen at any dose, although it is generally not clinically significant at standard dosages. Minor adverse effects include nausea and transient itching or urticaria from histamine release. Oversedation can be reversed with a competitive antagonist such as naloxone or nalmephine.
Morphine, the classic narcotic analgesic, is generally employed to treat moderate-to-severe pain, as an adjunct for painful procedures, and occasionally as a sedative hypnotic. For patients with a history of itching, it may be administered with diphenhydramine or hydroxyzine. Neonates and younger patients may need less per kilogram than patients older than 6 months. After this age, children younger than 11 years metabolize morphine more rapidly than adults, and may need more frequent redosing. Early use of intranasal or IV analgesic medications can aid in patient comfort and improved outcomes in trauma patients with NPO status.
Meperidine has clinical characteristics similar to those of morphine. Unlike morphine, it is metabolized to an active metabolite, normeperidine, which has a longer serum half-life than that of its parent compound. Increased levels of normeperidine can result in seizures thus it should not be used in children who will require multiple doses of a narcotic over an extended period.
Hydromorphone is a potent semisynthetic narcotic analgesic similar to morphine and meperidine and is frequently used in pain management protocols for renal colic pain, abdominal pain, or sickle cell anemia patients.
Fentanyl citrate is a synthetic short-acting narcotic approximately 100 times more potent than morphine. It has a rapid onset and 20-minute duration of action, making it ideal for brief painful procedures. Unlike other narcotics, fentanyl has few cardiovascular effects, making it attractive in hypovolemic or cardiac patients. A unique side effect of chest wall rigidity is seen when administered too rapidly (particularly in infants). The effect may be reversed with naloxone, although endotracheal intubation and skeletal muscle paralysis may be required. Fentanyl is the only narcotic administered through transmucosal routes. Overdosing and emesis led to the previously available “lollipop” to be removed from the market. Intranasal routes using the standard IV formulation have been safe in children as young as 1 year old.40 Mucosal atomization devices may increase medication delivery. Reduced doses should be used in neonates and very young infants, as they are more sensitive to the respiratory depressant effects.
Codeine, hydrocodone, and oxycodone are less potent narcotic analgesics generally administered orally in combination with a pure analgesic, such as acetaminophen or ibuprofen. Metabolism of codeine varies by race. Up to 15% of Asian patients and 7% to 10% of Caucasian patients have decreased ability to complete O-methylation which turns the codeine into the active morphine analog. Thus, these patients may experience no additional pain relief from the addition of codeine to the pure analgesic, which may explain a lack in comparative effectiveness in research comparing acetaminophen with and without codeine. Although the other two opioids are structurally similar, they appear to better metabolize into the active morphine. (See Table 13-1 for dosing of common pediatric analgesic agents.)
|
TABLE 13-1 |
Common Pediatric Analgesic Agents |
BEHAVIORAL PEDIATRIC PAIN MANAGEMENT
Multimodal approaches to pain management can improve outcomes by minimizing drug-induced adverse side effects while maximizing pain control.41 Behavioral recommendations often include coping skills training or providing distraction in preparation or implementation of the medical events. They include distraction, guided imagery, hypnosis, relaxation techniques, biofeedback, transcutaneous electrical nerve stimulation, and acupuncture.
PREPARATION (FOR CHILD AND PARENT)
Advanced preparation is in order for more complex procedures (e.g., surgery) or relatively minor procedures but perceived by the patient as traumatic. Same-day preparation is sufficient for minor medical events (e.g., venipuncture) and can be done in the ED setting. Preparation might include videos, written summaries, or other available aids and should combine diversion with didactic information. Allowing patients and their parents to ask questions may alleviate any fears or inaccurate expectations. Content should be clear and concise, presented in a non-emotive manner, age-appropriate, and contain details of the procedural steps and physical sensations a child should expect. Preparation should include training in coping skills, such as relaxation techniques (e.g., deep breathing, progressive muscle relaxation) or distraction (e.g., imagery, watching a movie, solving mental mathematics problems). As the parents’ own anxiety is predictive of their children’s medical distress, parents should learn how to best assist their child during painful medical procedures.42 Educating parents that self-blame increases the pain response, while focused distraction or hypnosis decreases it, may enable them to provide proper support.43
PROCEDURAL INTERVENTIONS
Behavioral interventions implemented during painful medical procedures often include relaxation, praise, and other reinforcement for appropriate behavior, imagery, and distraction. Distraction stimuli vary and include movies, interactive toys, virtual reality, music, bubbles, and short stories. Advances in technology provide options with devices that utilize features such as interactive touch screens and response to physical movement.44 Behaviorally, distraction diverts attention away from stimuli that have been classically conditioned to produce anxiety (e.g., medical equipment) or inducing behaviors that are incompatible with distress. The ideal distraction stimulus varies by individual, but ideally involves multiple sensory modalities (e.g., vision, hearing, touch) and produces positive emotions that are inconsistent with pain, such as laughing. Children engage in little coping without adults coaching them, thus stimuli should consider parents as coaches. Although one meta-analysis suggested that distraction was equally effective across gender and ethnic groups, but was most effective for children younger than 7 years of age, children of other ages still benefit. Distraction should be done prior to, during, and after the procedure.
BEHAVIORAL INTERVENTIONS FOR INFANTS
Data suggest that distraction might benefit children as young as 1 to 24 months of age, but is not as effective as for older toddlers.45 Recommended behavioral interventions for young infants include sucrose, nonnutritive sucking, breast feeding, and skin-to-skin contact (kangaroo care). Sucrose water given immediately prior to an acute painful procedure has been found to decrease pain in neonates and infants up to approximately 4 to 6 months of age. It is usually given by dipping a pacifier into a solution or instilling it directly into the mouth with a syringe.46
REFERENCES
1. Rupp T, Delaney KA. Inadequate analgesia in emergency medicine. Ann Emerg Med. 2004;43(4):494–503.
2. Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052):599–603.
3. Young KD. Pediatric procedural pain. Ann Emerg Med. 2005;45(2):160–171.
4. Weisman SJ, Bernstein B, Schechter NL. Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med. 1998;152(2):147–149.
5. Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 1998;14(1):9–17.
6. Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Good-enough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001;93(2):173–183.
7. Bulloch B, Garcia-Filion P, Notricia D, Bryson M, McConahay T. Reliability of the color analog scale: repeatability of scores in traumatic and nontraumatic injuries. Acad Emerg Med. 2009;16(5):465–469.
8. Frei-Jones MJ, Baxter AL, Rogers ZR, Buchanan GR. Vaso-occlusive episodes in older children with sickle cell disease: emergency department management and pain assessment. J Pediatr. 2008;152(2):281–285.
9. Voepel-Lewis T, Zanotti J, Dammeyer JA, Merkel S. Reliability and validity of the face, legs, activity, cry, consolability behavioral tool in assessing acute pain in critically ill patients. Am J Crit Care. 2010;19(1):55–61.
10. Crellin D, Sullivan TP, Babl FE, O’Sullivan R, Hutchinson A. Analysis of the validation of existing behavioral pain and distress scales for use in the procedural setting. Paediatr Anaesth. 2007;17(8):720–733.
11. American Academy of Pediatrics, Committee on Psychosocial Aspects of Child and Family Health, and American Pain Society, Task Force on Pain in Infants, Children, and Adolescents. The assessment and management of acute pain in infants, children, and adolescents. Pediatrics. 2001;108(3):793–797.
12. Eidelman A, Weiss JM, Lau J, Carr DB. Topical anesthetics for dermal instrumentation: a systematic review of randomized, controlled trials. Ann Emerg Med. 2005;46(4):343–351.
13. Chen BK, Cunningham BB. Topical anesthetics in children: agents and techniques that equally comfort patients, parents, and clinicians. Curr Opin Pediatr. 2001;13(4):324–330.
14. Baxter AL, Ewing PH, Young GB, Ware A, Evans N, Manworren RC. EMLA application exceeding two hours improves pediatric emergency department venipuncture success. Adv Emerg Nurs J. 2013;35(1):67–75.
15. Sawyer J, Febbraro S, Masud S, Ashburn MA, Campbell JC. Heated lidocaine/tetracaine patch (Synera, Rapydan™) compared with lidocaine/prilocaine cream (EMLA®) for topical anaesthesia before vascular access. Br J Anaesth. 2009;102(2):210–215.
16. Taddio A, Soin HK, Schuh S, Koren G, Scolnik D. Liposomal lidocaine to improve procedural success rates and reduce procedural pain among children: a randomized controlled trial. CMAJ. 2005;172(13):1691–1695.
17. O’Brien L, Taddio A, Lyszkiewicz DA, Koren G. A critical review of the topical local anesthetic amethocaine (Ametop) for pediatric pain. Paediatr Drugs. 2005;7(1):41–54.
18. Wallace MS, Kopecky EA, Ma T, Brophy F, Campbell JC. Evaluation of the depth and duration of anesthesia from heated lidocaine/tetracaine (SYNERA) patches compared with placebo patches applied to healthy adult volunteers. Reg Anesth Pain Med. 2010;35:507–513.
19. McNaughton C, Zhou C, Robert L, Storrow A, Kennedy R. A randomized, crossover comparison of injected buffered lidocaine, lidocaine cream, and no analgesia for peripheral intravenous cannula insertion. Ann Emerg Med. 2009;54(8):214–220..
20. Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM. A comparison of a needle-free injection system for local anesthesia versus EMLA for intravenous catheter insertion in the pediatric patient. Anesth Analg. 2006;102(2):41141–41144.
21. Pershad J, Steinberg SC, Waters TM. Cost-effectiveness analysis of anesthetic agents during peripheral intravenous cannulation in the pediatric emergency department. Arch Pediatr Adolesc Med. 2008;162(10):952–961.
22. Baxter AL, Cohen LL, McElvery HL, Lawson ML, von Baeyer CL. An integration of vibration and cold relieves venipuncture pain in a pediatric emergency department. Pediatr Emerg Care. 2011;27(12):1151–1156.
23. Farion KJ, Splinter KL, Newhook K, Gaboury I, Splinter WM. The effect of vapocoolant spray on pain due to intravenous cannulation in children: a randomized controlled trial. CMAJ. 179(1):31–36.
24. Resch K, Schilling C, Borchert BD, Klatzko M, Uden D. Topical anesthesia for pediatric lacerations: a randomized trial of lidocaine-epinephrine-tetracaine solution versus gel. Ann Emerg Med. 1998;32(6):693–697.
25. Priestley S, Kelly AM, Chow L, Powell C, Williams A. Application of topical local anesthetic at triage reduces treatment time for children with lacerations: a randomized controlled trial. Ann Emerg Med. 2003; 42(1):34–40.
26. Singer AJ, Stark MJ. LET versus EMLA for pretreating lacerations: a randomized trial. Acad Emerg Med. 2001;8(3):223–230.
27. Cooper DD, Seupaul RA. Does buffered lidocaine decrease the pain of local infiltration? Ann Emerg Med. 2012;59(4):281–282.
28. Chale S, Singer AJ, Marchini S, McBride MJ, Kennedy D. Digital versus local anesthesia for finger lacerations: a randomized controlled trial. Acad Emerg Med. 2006;13(10):1046–1050.
29. Cassidy-Smith T, Mistry RD, Russo CJ, et al. Topical anesthetic cream is associated with spontaneous cutaneous abscess drainage in children. Am J Emerg Med. 2012;30(1):104–109.
30. Hoyle JD Jr, Rogers AJ, Reischman DE, et al. Pain intervention for infant lumbar puncture in the emergency department: physician practice and beliefs. Acad Emerg Med. 2011;18(2):140–104.
31. Nigrovic LE, Kuppermann N, Neuman MI. Risk factors for traumatic or unsuccessful lumbar punctures in children. Ann Emerg Med. 2007;49(6):762–771.
32. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2010;1:CD001069.
33. Smith DP, Gjellum M. The efficacy of LMX versus EMLA for pain relief in boys undergoing office meatotomy. J Urol. 2004;172(4 Pt 2):1760–1761.
34. Mularoni PP, Cohen LL, DeGuzman M, Mennuti-Washburn J, Greenwald M, Simon HK. A randomized clinical trial of lidocaine gel for reducing infant distress during urethral catheterization. Pediatric Emergency Care. 2009;25(7):439–443.
35. Oswald J, Riccabona M, Lusuardi L, Ulmer H, Bartsch G, Radmayr C. Voiding cystourethrography using the suprapubic versus transurethral route in infants and children: results of a prospective pain scale oriented study. J Urol. 2002;168:2586–2589.
36. Birnbaum A, Esses D, Bijur PE, Holden L, Gallagher EJ. Randomized double-blind placebo-controlled trial of two intravenous morphine dosages (0.10 mg/kg and 0.15 mg/kg) in ED patients with moderate to severe acute pain. Ann Emerg Med. 2007;49(4):445–453.
37. Constantine E, Steele DW, Eberson C, Boutis K, Amanullah S, Linakis JG. The use of local anesthetic techniques for closed forearm fracture reduction in children: a survey of academic pediatric emergency departments. Pediatr Emerg Care. 2007;23(4):209–211.
38. Zuppa AF, Hammer GB, Barrett JS, et al. Safety and population pharmacokinetic analysis of intravenous acetaminophen in neonates, infants, children, and adolescents with pain or fever. J Pediatr Pharmacol Ther. 2011;16(4):246–261.
39. Promes JT, Safcsak K, Pavliv L, Voss B, Rock A. A prospective, multicenter, randomized, double-blind trial of IV ibuprofen for treatment of fever and pain in burn patients. J Burn Care Res. 2011;32(1):79–90.
40. Cole J, Shepherd M, Young P. Intranasal fentanyl in 1-3-year-olds: a prospective study of the effectiveness of intranasal fentanyl as acute analgesia. Emerg Med Australas. 2009;21(5):395–400.
41. Yaster M. Multimodal analgesia in children. Eur J Anaesthesiol. 2010;27(10):851–857.
42. Cohen LL. Reducing infant immunization distress through distraction. Health Psychol. 2002;21(2):207–211.
43. Langer DA, Chen E, Luhmann JD. Attributions and coping in children’s pain experiences. J Pediatr Psychol. 2005;30(7):615–622.
44 McQueen A, Cress C, Tothy A. Using a tablet computer during pediatric procedures: a case series and review of the “apps”. Pediatr Emerg Care. 2012;28(7):712–714.
45. Cohen LL, MacLaren JE, Fortson BL, et al. Randomized clinical trial of distraction for infant immunization pain. Pain. 2006;125(1–2):165–171.
46. Hatfield LA, Gusic ME, Dyer AM, Polomano RC. Analgesic properties of oral sucrose during routine immunizations at 2 and 4 months of age. Pediatrics. 2008;121(2):e327–e334.