American Burn Association Guidelines on the Management of Acute Pain in the Adult Burn Patient: A Review of the Literature, a Compilation of Expert Opinion and Next Steps

PURPOSE

The purpose of this guideline is to update the previous guideline by Drs Faucher and Furukawa.¹ To accomplish this, we review the principles of acute pain management in adult burn patients and present a reasonable approach to the management of the complex pain associated with burn injury based on a review of the literature and expert opinion. In addition, we provide suggestions for a research agenda that would yield evidence neccesary for the next iteration of recommendations for the treatment of acute pain associated with burn injury.

INTRODUCTION

Burn injury is widely considered one of the most painful injuries that a person can sustain. In addition to the intrinsic pain caused by the burn itself, the proper treatment of a burn injury requires painful procedures including debridment of the wound, daily wound care, and surgery, followed by aggressive physical and occupational therapy. Burn pain is especially complicated; it is multifaceted and frequently changes over time as the patient undergoes repeated procedures and treatments that require manipulation of their painful burn sites. Despite an understanding of the importance of pain management in recovery from burn wounds, numerous reports are discussing the inadequacy of treatment of burn pain. Furthermore, inconsistency in practice standards has been well documented for almost three decades.^2–6

TAXONOMY OF PAIN

The International Association for the Study of Pain (IASP) defines pain as “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” ⁷ Introduced in 1979, it is one of the most widely promulgated definitions for pain, including adoption by the World Health Organization. As our understanding of pain has advanced, there have been calls for an update to the original definition.^8–10 Nevertheless, the definition acknowledges that pain is a complex and multi-faceted phenomenon that includes subjective, psychosocial, and physiologic elements.

While the IASP definition of pain is widely utilized, there are several ways to categorize types of pain in neurological, physiological, and psychological domains. Published in 1965, Melzack and Wall’s “Pain mechanisms: A new theory,” introduced the Gate Theory of Pain.¹¹ Their work influenced subsequent pain research and provided neurophysiologic rationale and a mechanistic explanation for physical and psychologic aspects of pain and the development of chronic pain. Though many dispute specifics regarding the Gate Theory of Pain, the collective research on the neurophysiologic mechanisms of pain allow us to consider how pain signals are generated, promulgated, and perceived. Thus, pain can be described in terms of being somatogenic, nociceptive, neuropathic, and psychogenic as well as acute or chronic.

The pain caused by an acute burn injury is first and foremost nociceptive in nature. The process by which the noxious burn stimulus is interpreted as what we describe as pain occurs in several stages: transduction, conduction, transmission, modulation, and perception. The initiation of this process involves the activation of nociceptors in the skin. These stimuli are converted, or transduced, into electrophysiologic signals. The nociceptors are the terminals endings of C fibers (unmyelinated) and/or A-delta (AΔ fibers (myelinated) which conduct the signal from the peripheral nervous system centrally to the dorsal horn of the spinal cord. Transmission then occurs via the spinothalamic tracts to the brain. The processing of noxious stimuli occurs via both ascending and descending pathways and can be modulated by both excitatory and inhibitory mechanisms.

Several areas of the brain are involved in the perception of pain. These include the medulla, midbrain, and thalamus, then relayed to the somatosensory cortex, hypothalamus, hippocampus, and the amygdala. The involvement of these areas generates different perceptions of pain such as intensity, urgency, cognitive, and emotional aspects of the pain response. Via complex biochemical and electrophysiological mechanisms utilizing numerous receptors, cells, fibers, and neurotransmitters the painful sensation is processed in the central nervous system. Nevertheless, having at least a conceptual understanding of the stages of this process leads us to consider the utility and importance of multi-modal approaches to pain management. Knowledge of specific pathways and players involved in the process leads us to consider potential pharmacologic and nonpharmacologic treatments.

Rather than considering pain from an etiologic or physiologic/affective approach, pain can also be described in terms of an individual’s arc of recovery. Using this simpler taxonomy, pain can be described in terms of being background, breakthrough, or procedural in nature. Background (or baseline) pain exists while the patient is at rest and occurs from the burn injury itself. Breakthrough pain is instances when there is a transient exacerbation of pain. Procedural pain is pain associated with any therapeutic intervention with a patient, whether it is invasive (eg, arterial/venous access, wound debridement, and surgical) or noninvasive (eg, physical/occupational therapy).

Each of the approaches above provides a perspective to understanding the mechanisms and taxonomy of pain. They provide an important framework for the development and implementation of guidelines for pain management.

PROCESS

A sub-committee of the American Burn Association’s Committee on the Organization and Delivery of Burn Care was created to revise the previously published pain guidelines.¹ A MEDLINE search of the English-language publications from 1968 to 2018 was conducted using the keywords “burn pain,” “treatment,” and “assessment” as was described in the previously published guidelines. This search produced 189 results, of which 95 were found to be relevant to the assessment and treatment of burn pain. Additional selected references were also used based on the committee’s evaluation of the broader pain literature. Studies were sub-divided by topic and graded by 2 members of the committee per section using Oxford Centre for Evidence-based Medicine—Levels of Evidence.¹² When there was a disagreement about the grade of a particular study a third member of the committee was used to resolve the disagreement. These articles were compiled into an evidence-based review of current knowledge regarding treatment of burn-related pain. Please see Table 1 for all included papers and their level of evidence grading and Table 2 for a description of the level of evidence. The next step was an in-person meeting to determine expert consensus on a variety of topics related to the treatment of pain in burn-injured patients. The committee consisted of a wide range of burn care providers including burn surgeons, burn nurses, anesthesiologists, a pharmacist, and a psychologist. All members had significant interest and experience caring for burn injured patients. Finally, we assessed gaps in current knowledge and proposed research questions that would provide evidence for future recommendations. In this article, we address interventions used to ameliorate the profound and (at this point) inevitable pain patients experience in the course of acute burn care. Though outside the scope of this review, it should be noted that thoughtful wound management—prompt surgical coverage where indicated, preventing wound infection, and wound care approaches that reduce the frequency of dressing changes—play a crucial role in minimizing the pain a patient experiences.

Table 1.

Evidence-based literature review of current knowledge regarding treatment of burn-related pain

Topic	Reference (numbers in italics are reference number from manuscript)	Data class
Pain assessment	Ashburn MA. Burn pain: the management of procedure-related pain. J Burn Care Rehabil 1995;16(3 Pt 2):365–71. (13)	Level 5, grade D
	Browne AL et al. Persistent pain outcomes and patient satisfaction with pain management after burn injury. Clin J Pain 2001;27(2):136–45.	Level 4, grade C
	Carrougher GJ et al. Comparison of patient satisfaction and self-reports of pain in adult burn-injured patients. J Burn Care Rehab 2003;24(1):1–8. (2)	Level 2c, grade B
	Casser HR et al. Multidisciplinary assessment for multimodal pain therapy. Indications and range of performance. Schmerz 2013;27(4):363–70.	Level 5, grade D
	Choiniere M et al. The pain of burns: characteristics and correlates. J Trauma 1989;29:1531–9. (3)	Level 4, grade C
	Connor-Ballard PA. Understanding and managing burn pain: part 1. Am J Nurs 2009;109(4): 48–56; quiz 57.	Level 5, grade D
	Connor-Ballard PA. Understanding and managing burn pain: Part 2. Am J Nurs 2009;109(5): 54–62; quiz 63.	Level 5, grade D
	de Castro RJ et al. Pain management in burn patients. Braz J Anesthesiol 2013;63(1):149–53. (14)	Level 5, grade D
	de Jong AE et al. The visual analogue thermometer and the graphic numeric rating scale: a comparison of self-report instruments for pain measurement in adults with burns. Burns 2015;41(2):333–40. (31)	Level 2b, grade B
	de Jong AE et al. Pain in young children with burns: extent, course and influencing factors. Burns 2014;40(1):38–47. (20)	Level 2b, grade C
	de Jong A et al. Reliability, validity and clinical utility of three types of pain behavioural observation scales for young children with burns aged 0–5 years. Pain 2010;150(3):561–7.	Level 2b, grade C
	de Jong AE et al. Reliability and validity of the pain observation scale for young children and the visual analogue scale in children with burns. Burns 2005;31(2):198–204. (30)	Level 4, grade C
	Echevarria-Guanilo ME et al. Reliability and validity of the Brazilian-Portuguese version of the Burns Specific Pain Anxiety Scale (BSPAS). Int J Nurs Stud 2011;48(1):47–55.	Level 2c, Grade B
	Esfahlan AJ et al. Burn pain and patients’ responses. Burns 2010;36(7):1129–33.	Level 2b; grade C
	Gelinas C. Pain assessment in the critically ill adult: recent evidence and new trends. Intensive Crit Care Nurs 2016;34: 1–11. (25)	Level 5, grade D
	Griggs C et al. Sedation and pain management in burn patients. Clin Plast Surg 2017;44(3): 535–40.	Level 5, grade D
	Gamst-Jensen H et al. Acute pain management in burn patients: appraisal and thematic analysis of four clinical guidelines. Burns 2014;40(8):1463–9.	Level 5 grade D
	Gordon M et al. Use of pain assessment tools: is there a preference? J Burn Care Rehabil 1998;19(5):451–4. (32)	Level 1b, grade B
	Jonsson CE et al. Background pain in burn patients: routine measurement and recording of pain intensity in a burn unit. Burns 1998;24(5):448–54. (21)	Level 2b, grade B
	Kohler H et al. Pain management in children: assessment and documentation in burn units. Eur J Pediatr Surg 2001;11(1):40–3. (16)	Level 2C grade C
	Mahar PD et al. Frequency and use of pain assessment tools implemented in randomized controlled trials in the adult burns population: a systematic review. Burns 2012;38(2):147–54. (34)	Level 2a, grade B
	Martin-Herz SP et al. Pediatric pain control practices of North American Burn Centers. J Burn Care Rehab 2003;24(1):26–36.	Level 2c grade C
	McGhee LL et al. The relationship of early pain scores and posttraumatic stress disorder in burned soldiers. J Burn Care Res 2011;32(1):46–51.	Level 3b, grade C
	Myers R et al. Sedation and analgesia for dressing change: a survey of American Burn Association Burn Centers. J Burn Care Res 2017;38(1):e48–54.	Level 2c, grade C
	Payen JF et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 2001;29(12):2258–63. (24)	Level 4, grade C
	Perez Boluda MT et al. The dynamic experience of pain in burn patients: a phenomenological study. Burns 2016;42(5):1097–04. (17)	Level 4, grade C
	Perry S et al. Assessment of pain by burn patients. J Burn Care Rehabil 1981;2:322–7. (4)	Level 4, grade C
	Ptacek J et al. Pain, coping and adjustment in patients with burns: preliminary findings from a prospective study. J Pain Symptom Manage 1995;10:446–55. (5)	Level 2b, grade B
	Radnovich R et al. Acute pain: effective management requires comprehensive assessment. Postgrad Med 2014;126(4):59–72. (35)	Level 5 grade D
	Rae CP et al. An audit of patient perception compared with medical and nursing staff estimation of pain during burn dressing changes.” Eur J Anaesthesiol 2000;17(1):43–5.	Level 4, grade C
	Ratcliff SL et al. The effectiveness of a pain and anxiety protocol to treat the acute pediatric burn patient. Burns 2006;32(5):554–62.	Level 3b, grade C
	Richardson P, Mustard L. The management of pain in the burns unit. Burns 2009;35(7):921–36.	Level 5, grade D
	Robert R et al. Anxiety: current practices in assessment and treatment of anxiety of burn patients. Burns 2000;26(6):549–52. (37)	Level 4, grade C
	Shen J et al. Evaluation of nurse accuracy in rating procedural pain among pediatric burn patients using the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. Burns 2017;43(1):114–20. (33)	Level 2b, grade B
	Singer AJ et al. Association between burn characteristics and pain severity. Am J Emerg Med 2015;33(9):1229–31.	Level 3b, grade C
	Springborg AD et al. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model: a study protocol: a randomized, double-blind, placebo-controlled, crossover trial with an enriched design. Medicine 2016;95(46):e5336.	Level 1b, grade A
	Stites M. Observational pain scales in critically ill adults. Crit Care Nurse 2013;33:68–78.	Level 5, grade D
	Stoddard FJ et al. Treatment of pain in acutely burned children. J Burn Care Rehabil 2002;23(2):135–56.	Level 5, grade D
	Summer GJ et al. Burn injury pain: the continuing challenge. J Pain 2007;8(7):533–48.	Level 5, grade D
	Taal LA, Faber AW. The burn specific pain anxiety scale: introduction of a reliable and valid measure. Burns 1997;23(2):147–50. (18)	Level 2b, grade B
	Taal LA et al. The abbreviated burn specific pain anxiety scale: a multicenter study. Burns 1999;25(6):493–7. (19)	Level 2b, grade C
	Taverner T, Prince J. Acute neuropathic pain assessment in burn injured patients: a retrospective review. J Wound Ostomy Continence Nurs 2016;43(1):51–5. (36)	Level 2b, grade C
	Topolovec-Vranic J et al. Validation and evaluation of two observational pain assessment tools in a trauma and neurosurgical intensive care unit. Pain Res Manag 2013;18(6):e107–14.	Level 5, grade D
	Turk DC et al. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on methods, measurement, and pain assessment in clinical trials. Pain 2008;139(3):485–93.	Level 5, grade D
	Wasiak J et al. Inhaled methoxyflurane for pain and anxiety relief during burn wound care procedures: an Australian case series. Int Wound J 2014;11(1):74–8.	Level 4, grade C
	Weddell R. Improving pain management for patients in a hospital burns unit. Nurs Times 2004;100(11):38–40.	Level 5, grade D
	Weinberg K et al. Pain and anxiety with burn dressing changes: patient self-reports. J Burn Care Rehabil 2000;21:157–161. (6)	Level 4, grade C
	Wibbenmeyer L. et al. An evaluation of factors related to postoperative pain control in burn patients. J Burn Care Res 2015;36(5):580–6. (40)	Level 3b, grade C
	Wibbenmeyer L. et al. Evaluation of the usefulness of two established pain assessment tools in a burn population. J Burn Care Res 2011;32:52–60.	Level 3b, grade C
	Williams DA. The importance of psychological assessment in chronic pain. Curr Opin Urol 2013;23(6):554–9.	Level 5, grade D
	Yang CL, Wei ZR. Advances in the research of burn pain. Zhonghua Shao Shang Za Zhi 2017;33(1):61–4.	Level 5, grade D
	Yang HT et al. Improvement of burn pain management through routine pain monitoring and pain management protocol. Burns 2013;39(4):619–24. (15)	Level 1b, grade A
Pharmacologic treatments
Opioid pain medication	Altier N et al. Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study. Burns 2001;27(7):771–5.	Level 4, grade C
	Andrews RM. Predictors of patient satisfaction with pain management and improvement 3 months after burn injury. J Burn Care Res 2012;33(3):442–52.	Level 2b, grade B
	Borland ML et al. Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: a randomised double blind crossover study. Burns 2005;31(7):831–7. (48)	Level 1b, grade B
	Chen L et al. Prediction of effect-site concentration of sufentanil by dose-response target controlled infusion of sufentanil and propofol for analgesic and sedation maintenance in burn dressing changes. Burns 2014;40(3):455–9. (52)	Level 2b, grade B
	Corkery JM et al. The effects of methadone and its role in fatalities. Hum Psychopharmacol 2004;19:565–76.	Level 5, grade D
	Cuignet O et al. Effects of gabapentin on morphine consumption and pain in severely burned patients. Burns 2007;33(1):81–6.	Level 3b, grade C
	Finn J et al. A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns. Burns 2004;30(3):262–8. (49)	Level 1b, grade B
	Foertsch CE et al. A quasi-experimental, dual-center study of morphine efficacy in patients with burns. J Burn Care Rehabil 1995;16(2 Pt 1):118–26. (38)	Level 1b, grade A
	Gallagher G et al. The use of a target-controlled infusion of alfentanil to provide analgesia for burn dressing changes a dose finding study. Anesthesia 2000;55:1159–63. (55)	Level 4, grade C
	Grimsrud KN et al. Identification of cytochrome P450 polymorphisms in burn patients and impact on fentanyl pharmacokinetics: a pilot study. J Burn Care Res 2019;40(1):91–6. (44)	Level 4, grade C
	Holtman JR Jr., Jellish WS. Opioid-induced hyperalgesia and burn pain. J Burn Care Res 2012;33(6):692–701.	Level 5, grade D
	Inturrisi CE. Pharmacology of methadone and its isomers. Minerva Anestesiol 2005;71:435–7.	Level 5, grade D
	Jones GM et al. Impact of early methadone initiation in critically injured burn patients: a pilot study. J Burn Care Res 2013;34:342–8. (41)	Level 4, grade C
	Kim DE et al. A review of adjunctive therapies for burn injury pain during the opioid crisis. J Burn Care Res 2019;40(6):983–95. (43)	Level 5, grade D
	Latarjet J, Choinère M. Pain in burn patients. Burns 1995;21(5):344–8.	Level 5, grade D
	Layson-Wolf C et al. Clinical use of methadone. J Pain Palliat Care Pharmacother 2002;16:29–59.	Level 5, grade D
	Le Floch R et al. Use of remifentanil for analgesia during dressing change in spontaneously breathing non-intubated burn patients. Ann Burns Fire Disasters 2006;19:136–9. (53)	Level 4, grade C
	Lilleso J et al. Effect of peripheral morphine in a human model of acute inflammatory pain. Br J Anaesthe 2000;85(2):228–32.	Level 1b, grade B
	Linneman PK et al. The efficacy and safety of fentanyl for the management of severe procedural pain in patients with burn injuries. J Burn Care Rehabil 2000;216:519–22. (47)	Level 1b, grade B
	Long TD et al. Morphine-infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot study. J Burn Care Rehabili 2001;22(2):118–23.	Level 2b, grade B
	Lugo RA et al. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005;19:13–24.	Level 5, grade D
	Martin-Herz SP et al. Pediatric pain control practices of North American Burn Centers. J Burn Care Rehabili 2003;24(1):26–36.	Level 5, grade D
	McIntyre MK et al. Progress of clinical practice on the management of burn-associated pain: lessons from animal models. Burns 2016;42(6):1161–72.	Level 5, grade D
	McSherry T et al. Randomized, crossover study of immersive virtual reality to decrease opioid use during painful wound care procedures in adults. J Burn Care Res 2018;39(2):278–85.	Level 2b, grade B
	Ng JWG et al. Management of the lower gastrointestinal system in burn: a comprehensive review. Burns 2016;42(4):728–37.	Level 5, grade D
	Nilsson A et al. Patient controlled sedation using a standard protocol for dressing changes in burns: patients' preference, procedural details and a preliminary safety evaluation. Burns 2008;34(7):929–34. (56)	Level 2b, grade B
	Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010;363(21):1981–5.	Level 5, grade D
	Pardesi O et al. Pain Management in pediatric burn patients: review of recent literature and future directions. J Burn Care Res 2017;38(6):335–47.	Level 5, grade D
	Patterson DR et al. Baseline pain as a moderator of hypnotic analgesia for burn injury treatment. J Consul Clin Psychol 1997;65(1):60–7.	Level 2b, grade B
	Patterson DR et al. The 2002 Lindberg Award. PRN vs regularly scheduled opioid analgesics in pediatric burn patients. J Burn Care Rehabili 2002;23(6):424–30.	Level 3A, grade B
	Prakash S et al. Patient-controlled analgesia with fentanyl for burn dressing changes. Anesth Analg 2004;99(2):552–5.	Level 1b, grade B
	Ratcliff SL et al. The effectiveness of a pain and anxiety protocol to treat the acute pediatric burn patient. Burns 2006;32(5):554–62.	Level 4, grade C
	Retrouvey H, Shahrokhi S. Pain and the thermally injured patient-a review of current therapies. J Burn Care Res 2015;36(2):315–23. (59)	Level 5, grade D
	Richardson P, Mustard L. The management of pain in the burns unit. Burns 2009;35(7):921–36.	Level 5, grade D
	Rittner HL et al. The clinical (ir)relevance of opioid-induced immune suppression. Curr Opin Anaesthesiol 2010;23(5):588–92.	Level 4, grade C
	Robert R et al. A double-blind study of the analgesic efficacy of oral transmucosal fentanyl citrate and oral morphine in pediatric patients undergoing burn dressing change and tubbing. J Burn Care Rehabili 2003;24:351–5. (51)	Level 2b, grade C
	Schulte H et al. The synergistic effect of combined treatment with systemic ketamine and morphine on experimentally induced windup-like pain in humans. Anesth Analg 2004;98(6): 1574–80.	Level 2b, grade B
	Shah H et al. Factors in the choice of oral transmucosal fentanyl citrate dose for adult burns dressings. Burns 2009;35(6):798–801. (46)	Level 3b, grade C
	Sharar SR et al. A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. J Burn Care Rehabili 2002;23(1):27–31. (50)	Level 2b, grade B
	Sharar SR et al. A comparison of oral transmucosal fentanyl citrate and oral hydromorphone for inpatient pediatric burn wound care analgesia. J Burn Care Rehabili 1998;19(6):516–21.	Level 2b, grade B
	Shelley K, Paech MJ. The clinical applications of intranasal opioids. Curr Drug Deliv 2008;5(1):55–8.	Level 5, grade D
	Sheridan R et al. Multi-center benchmarking study. Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: effects durable at 4 years. J Trauma Acute Care Surg 2014;76(3):828–32. (39)	Level 2b, grade B
	Seol TK et al. Propofol-ketamine or propofol-remifentanil for deep sedation and analgesia in pediatric patients undergoing burn dressing changes: a randomized clinical trial. Paediatr Anaesth 2015;25(6):560–6. (54)	Level 2b, grade C
	Stein C, Küchler S. Non-analgesic effects of opioids: peripheral opioid effects on inflammation and wound healing. Curr Pharm Des 2012;18(37):6053–69.	Level 5, grade D
	Sullivan SR et al. “Opioid creep” is real and may be the cause of “fluid creep. Burns 2014;30(6):583–90.	Level 2b, grade C
	Thompson EM et al. Efficacy and safety of procedural sedation and analgesia for burn wound care. J Burn Care Res 2012;33(4):504–9.	Level 3b, grade C
	Trupkovic T et al. Analgesia and sedation in the intensive care of burn patients: results of a European survey. J Intensive Care Med 2011;26:397–407.	Level 5, grade D
	Webster LR. Risk factors for opioid-use disorder and overdose. Anesth Analg 2017;125(5): 1741–8.	Level 5, grade D
	Welling A. A randomised controlled trial to test the analgesic efficacy of topical morphine on minor superficial and partial thickness burns in accident and emergency departments. Emerg Med J 2007;24(6):408–12.	Level 2a, grade B
	Wibbenmeyer L et al. The impact of opioid administration on resuscitation volumes in thermally injured patients. J Burn Care Res 2010;31(1):48–56.	Level 4, grade C
	Williams PI et al. Use of methadone in the morphine-tolerant burned paediatric patient. Br J Anaesth 1998;80:92–5. (42)	Level 4, grade C
	Yang C et al. Efficacy and feasibility of opioids for burn analgesia: an evidence-based qualitative review of randomized controlled trials. Burns 2018;44(2):241–8.	Level 3b, grade C
	Zor F et al. Pain relief during dressing changes of major adult burns: ideal analgesic combination with ketamine. Burns 2010;36(4):501–5.	Level 3b, grade C
Nonopioid medication	Asmussen S et al. A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients. Burns 2013;39(4):625–31.	Level 2a, grade B
	Bestard JA, Toth CC. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the management of neuropathic pain in patients with peripheral neuropathy. Pain Practice 2011;11:353–68. (93)	Level 4, grade C
	Canpolat DG et al. Ketamine-propofol vs ketamine-dexmedetomidine combinations in pediatric patients undergoing burn dressing changes. J Burn Care Res 2012;33(6):718–22. (78)	Level 2b, grade B
	Carstensen M, Moller AM. Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials. Br J Anaesth 2010;104(4):401–6.	Level 2a, grade B
	Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs 1996;52 (Suppl 5):13–23. (61)	Level 5, grade D
	Coimbra C et al. Patient-controlled sedation using propofol for dressing changes in burn patients: a dose-finding study. Anesth Analg 2003;97(3):839–42.	Level 4, grade C
	Cuignet O et al. Effects of gabapentin on morphine consumption and pain in severely burned patients. Burns 2007;33(1):81–86. (68)	Level 3b, grade C
	Davis KD et al. Cutaneous pretreatment with the capsaicin analog NE-21610 prevents the pain to a burn and subsequent hyperalgesia. Pain 1995;62(3):373–8.	Level 4, grade C
	Desai C et al. Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes: a double-blinded randomised pilot trial comparing an emulsion with an aqueous lidocaine formulation. Burns 2014;40(1):106–12.	Level 1b, grade B
	Dworkin RH et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132(3):237.	Level 5, grade D
	Edrich T et al. Ketamine for long-term sedation and analgesia of a burn patient. Anesth Analg 2004;99(3):893–5. (77)	Level 5 grade D
	Everett JJ et al. Adjunctive interventions for burn pain control: comparison of hypnosis and ativan: the 1993 Clinical Research Award. J Burn Care Rehabili 1993;14(6):676–83.	Level 4, grade C
	Frank B et al. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomized, crossover, double blind study. BMJ 2008;336:199–201. (92)	Level 1b, grade B
	Graham GG, Scott KF. Mechanisms of action of paracetamol. Am J Ther 2006;12:46–55. (57)	Level 5, grade D
	Gray P et al. Pregabalin in severe burn injury pain: a double-blind, randomised placebo-controlled trial. Pain 2011;152(6):1279–88. (71)	Level 1b, grade B
	Gray P et al. Successful use of gabapentin in acute pain management following burn injury: a case series. Pain Med 2008;9(3):371–6. (65)	Level 4, grade C
	Green DP et al. Role of endogenous TRPV1 agonists in a postburn pain model of partial-thickness injury. Pain 2013;154(11):2512–20.	Level 2b, grade B
	Hansen SL et al. A retrospective study on the effectiveness of intranasal midazolam in pediatric burn patients. J Burn Care Rehabili 2001;22(1):6–8.	Level 4, grade C
	Heinrich M et al. Conscious sedation: off-label use of rectal S(+)-ketamine and midazolam for wound dressing changes in paediatric heat injuries. Eur J Pedia Surg 2004;14(4):235–9.	Level 4, grade C
	Jonsson A et al. Inhibition of burn pain by intravenous lignocaine infusion. Lancet 1991;338(8760):151–2.	Level 4, grade C
	Kariya N et al. Oral clonidine for sedation and analgesia in a burn patient. J Clin Anesth 1998;10(6):514–7.	Level 4, grade C
	Kaul I et al. Use of gabapentin and pregabalin for pruritus and neuropathic pain associated with major burn injury: a retrospective chart review. Burns 2018;44(2):414–22.	Level 4, grade C
	Kaur S et al. Effect of intraoperative infusion of low-dose ketamine on management of postoperative analgesia. J Nat Sci Biol Med 2015;6:378–82. (75)	Level 2b, grade B
	Kundra P et al. Oral ketamine and dexmedetomidine in adults' burns wound dressing—A randomized double blind cross over study. Burns 2013;39(6):1150–6. (79)	Level 1b, grade B
	Lee JJ et al. Effectiveness of nalbuphine for relief of burn debridement pain. J Burn Care Rehabili 1989;10(3):241–6.	Level 2b, grade B
	Lu S et al. A double blind placebo control pilot study on the safety and tolerability of Nabilone in marijuana users. Mental Health Subs Use 2013;6:133–9.	Level 2b, grade B
	Loftus RW et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010;113:639–46. (73)	Level 1b, grade B
	Lyons B et al. Pain relief with low-dose intravenous clonidine in a child with severe burns. Intensive Care Med 1996;22(3):249–51. (87)	Level 5, grade D
	Maani CV et al. Combining ketamine and virtual reality pain control during severe burn wound care: one military and one civilian patient. Pain Med 2011;12(4):673–8.	Level 5, grade D
	MacPherson RD et al. Ketamine and midazolam delivered by patient-controlled analgesia in relieving pain associated with burns dressings. Clin J Pain 2008;24(7):568–71. (80)	Level 4, grade C
	Marinangeli F et al. Clonidine for treatment of postoperative pain: a dose-finding study. Eur J Pain 2002;6:35–42. (86)	Level 1b, grade B
	Martin E et al. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med 2003;18:29–41. (83)	Level 1b, grade A
	McGuinness SK et al. A systematic review of ketamine as an analgesic agent in adult burn injuries. Pain Med 2011;12(10):1551–8. (76)	Level 2a, grade B
	Meyer WJ, 3rd et al. Acetaminophen in the management of background pain in children post-burn. J Pain Symptom Manage 1997;13(1):50–5. (60)	Level 4, grade C
	Nauta M et al. Codeine-acetaminophen versus nonsteroidal anti-inflammatory drugs in the treatment of post-abdominal surgery pain: a systematic review of randomized trials. Am J Surg 2009;198(2):256–61. (64)	Level 1a, grade A
	Norambuena C et al. Oral ketamine and midazolam for pediatric burn patients: a prospective, randomized, double-blind study. J Pediatr Surg 2013;48(3):629–34.	Level 1b, grade A
	Orrey DC et al. Results of a pilot multicenter genotype-based randomized placebo-controlled trial of propranolol to reduce pain after major thermal burn injury. Clin J Pain 2015;31(1):21–9.	Level 1a, grade A
	Owens VF et al. Ketamine: a safe and effective agent for painful procedures in the pediatric burn patient. J Burn Care Res 2006;27(2):211–6. (81)	Level 4, grade C
	Pal SK et al. Adjunctive methods of pain control in burns. Burns 1997;23:404–12. (58)	Level 5, grade D
	Pedersen JL et al. Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in thermal injury. Br J Anaesth 1994;72(4):379–82.	Level 1b, grade B
	Pichot C et al. Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting? J Intensive Care Med 2012;27:219–37. (88)	Level 5, grade D
	Promes JT et al. 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. (63)	Level 2b, grade B
	Retrouvey H, Shahrokhi S. Pain and the thermally injured patient—a review of current therapies. J Burn Care Res 2015;36(2):315–23. (59)	Level 5, grade D
	Shank ES et al. Hemodynamic responses to dexmedetomidine in critically injured intubated pediatric burned patients: a preliminary study. J Burn Care Res 2013;34(3):311–17. (84)	Level 4, grade C
	Springborg AD et al. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model: a study protocol: a randomized, double-blind, placebo-controlled, crossover trial with an enriched design. Medicine 2016;95(46):e5336.	Level 1b, grade B
	Tran HT et al. Intravenous ketorolac for pain management in a ventilator-dependent patient with thermal injury. Pharmacotherapy 1996;16(1):75–8. (62)	Level 5, grade D
	Tryba M, Gehling M. Clonidine—a potent analgesic adjuvant. Curr Opin Anaesthesiol 2002;15:511–7. (85)	Level 5, grade D
	Turcotte D et al. Examining the roles of cannabinoids in pain and other therapeutic indications: a review. Expert Opin Pharmaco 2010;11:17–31. (91)	Level 2a, grade B
	Wasiak J et al. Intravenous lidocaine for the treatment of background or procedural burn pain. Cochr Datab Syst Rev 2012;6:CD005622. (90)	Level 1a, grade A
	Webb AR et al. The addition of a small-dose ketamine infusion to tramadol for postoperative analgesia: a double-blinded, placebo-controlled, randomized trial after abdominal surgery. Anesth Analg 2007;104:912–7. (74)	Level 1b, grade B
	Werner MU et al. Analgesic effects of dexamethasone in burn injury. Reg Anesth Pain Med 2002;27(3):254–60.	Level 1b, grade B
	Wibbenmeyer L et al. Gabapentin is ineffective as an analgesic adjunct in the immediate postburn period. J Burn Care Res 2014;35(2):136–42. (69)	Level 1b, grade B
	Wong L, Turner L. Treatment of post-burn neuropathic pain: evaluation of pregablin. Burns 2010;36:769–72. (70)	Level 4, grade C
	Zhang J et al. Effects of puerarin on the inflammatory role of burn-related procedural pain mediated by P2X(7) receptors. Burns 2013;39(4):610–8.	Level 3b, grade C
	Zor F. et al. Pain Relief during dressing changes of major adult burns: ideal analgesic combination with Ketamine. Burns 2010;36(4): 501–5. (82)	Level 2b, grade B
Regional anesthesia	Ashburn MA. Burn pain: the management of procedure-related pain. J Burn Care Rehabil 1995;16(3 pt 2):365–71.	Level 5, grade D
	Burd A, Ahmed K. Staged serial debridement and one stage grafting under local anaesthesia. A bed side procedure. Burns 2010;36(4):588–9.	Level 5, grade D
	Bussolin L et al. Tumescent local anesthesia for the surgical treatment of burns and postburn sequelae in pediatric patients. Anesthesiology 2003;99(6):1371–5. (97)	Level 2b, grade B
	Bussolin L et al. Plasma levels of lignocaine during tumescent local anaesthesia in children with burns. Anaesth Intens Care 2010;38(6):1008–12. (96)	Level 3b, grade C
	Cuignet O et al. The efficacy of continuous fascia iliaca compartment block for pain management in burn patients undergoing skin grafting procedures. Anesth Analg 2004;98(4):1077–81. (101)	Level 1b, grade B
	Cuignet O et al. The long-term analgesic efficacy of a single-shot fascia iliaca compartment block in burn patients undergoing skin-grafting procedures. J Burn Care Rehabil 2005;26(5): 409–15. (102)	Level 1b, grade B
	Dahl JB et al. The effect of pre- versus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin. Pain 1993;53(1):43–51.	Level 3b, grade C
	Gupta A et al. A study of regional nerve blocks and local anesthetic creams (Prilox) for donor sites in burn patients. Burns 2007;33(1):87–91.	Level 3b, grade C
	Harbin KR, Norris TE. Anesthetic management of patients with major burn injury. AANA J 2012;80(6):430–9.	Level 5, grade D
	Janezic TF. Skin grafting of full thickness burns under local anaesthesia with EMLA cream. Burns 1998;24(3):259–63. (95)	Level 5, grade D
	Jellish WS et al. Effect of topical local anesthetic application to skin harvest sites for pain management in burn patients undergoing skin-grafting procedures. Ann Surg 1999;229(1):115–20. (94)	Level 2b, grade B
	Kestenbaum AD et al. Doppler-guided axillary block in a burn patient. Anesthesiology 1990;73(3):586–7.	Level 5, grade D
	Mago V, Prasad M. Tumescent local anesthesia for release of postburn neck contractures. J Burn Care Res 2009;30(6):1049.	Level 5, grade D
	Mora AG et al. En route use of analgesics in nonintubated, critically ill patients transported by U.S. Air Force critical care air transport teams. Mil Med 2016;181(5 Suppl):145–51.	Level 4, grade C
	Pardesi O, Fuzaylov G. Pain management in pediatric burn patients: review of recent literature and future directions. J Burn Care Res 2017;38(6):335–47.	Level 4, grade C
	Pedersen JL et al. Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury. Anesthesiology 1996;84(5):1020–6. (103)	Level 4, grade C
	Prasad MK et al. Severe post-burn neck contracture release and skin graft harvest using tumescent local anaesthesia as the sole anesthetic technique. J Anesth 2012;26(1):97–99. (98)	Level 5, grade D
	Prasetyono TO, Koswara AF. Linear hand burn contracture release under local anesthesia without tourniquet. Hand Surg 2015;20(3):484–7.	Level 5, grade D
	Randalls B. Continuous brachial plexus blockade. a technique that uses an axillary catheter to allow successful skin grafting. Anaesthesia 1990;45(2):143–4.	Level 5, grade D
	Shank ES et al. Ultrasound-guided regional anesthesia for pediatric burn reconstructive surgery: a prospective study. J Burn Care Res 2016;37(3):e213–7. (100)	Level 5, grade D
	Shick V et al. The benefits of ultrasound-guided continuous sensory nerve blockade in the setting of burn injury: a case report of bilateral continuous superficial peroneal nerve blockade in a patient with severe sleep apnea. J Clin Anesth 2017;36:62–6.	Level 5, grade D
	Shteynberg A et al. Ultrasound guided lateral femoral cutaneous nerve (LFCN) block: safe and simple anesthesia for harvesting skin grafts. Burns 2013;39(1):146–9. (99)	Level 3b, grade C
	Wasiak J et al. Adjuvant use of intravenous lidocaine for procedural burn pain relief: a randomized double blind, placebo-controlled, crossover trial.” Burns 2011;37:951–7. (91)	Level 1b, grade B
Non-pharmacologic treatments
General	de Jong AEE et al. Nonpharmacological nursing interventions for procedural pain relief in adults with burns: a systematic literature review. Burns 2007;33:811–27. (104)	Level 3a, grade B
	Everett JJ et al. Cognitive and behavioral treatments for burn pain. Pain Clin 1990;3:133–45.	Level 5, grade D
	Fauerbach JA et al. Coping with the stress of a painful medical procedure. Behav Res Ther 2002;40(9):1003–15. (112)	Level 1b, grade A
	Hanson MD et al. Nonpharmacological interventions for acute wound care distress in pediatric patients with burn injury: a systematic review. J Burn Care Res 2008;29:730–41. (106)	Level 2b, grade B
	Martin-Herz SP et al. Psychological principles of burn wound pain in children: part II: treatment applications. J Burn Care Rehabil 2000;21(5):458–72.	Level 5, grade D
	Scheffler M et al. Efficacy of non-pharmacological interventions for procedural pain relief in adults undergoing burn wound care: a systematic review and meta-analysis of randomized controlled trials. Burns 2018;44(7):1709–20. (105)	Level 1a, grade A
	Thurber CA et al. Psychological principles of burn wound pain in children: part I: theoretical framework. J Burn Care Rehabil 2000; 21(4):376–87.	Level 5, grade D
Hypnosis	Askay SW et al. A randomized controlled trial of hypnosis for burn wound care. Rehabili Psychol 2007;52:247–53.	Level 1b, Grade A
	Berger MM et al. Impact of a pain protocol including hypnosis in major burns. Burns 2010;36(5):639–46. (113)	Level 2c, Grade B
	Chester SJ et al. Effectiveness of medical hypnosis for pain reduction and faster wound healing in pediatric acute burn injury: study protocol for a randomized controlled trial. Trials 2016;17(1):223. (111)	Level 5, grade D
	Everett JJ et al. Adjunctive interventions for burn pain control: comparison of hypnosis and ativan: the 1993 Clinical Research Award. J Burn Care Rehabili 1993;14(6):676–83.	Level 2b, grade B
	Frenay MC et al. Psychological approaches during dressing changes of burned patients: a prospective randomised study comparing hypnosis against stress reducing strategy. Burns 2001;27(8):793–9.	Level 1b, grade B
	Patterson DR et al. Hypnotherapy as a treatment for pain in patients with burns: research and clinical considerations. J Burn Care Rehabil 1987;8:263–8.	Level 3a, grade B
	Patterson DR et al. Hypnosis for the treatment of burn pain. J Consul Clin Psychol 1992;60: 713–7. (108)	Level 2b, grade B
	Patterson DR, Ptacek JT. Baseline pain as a moderator of hypnotic analgesia for burn injury treatment. J Consul Clin Psychol. 1997;65:60–7.	Level 2b, grade B
	Patterson DR, Jensen M. Hypnosis and Clinical Pain. Psychol Bull 2003;129:495–521.	Level 5, grade D
	Patterson DR et al. Factors predicting hypnotic analgesia in clinical burn pain. Int J Clin Exper Hypn 1997;45:377–95.	Level 5, grade D
	Patterson DR et al. Hypnotherapy as an adjunct to narcotic analgesia for the treatment of pain for burn debridement. Amer J Clin Hypn 1989;31:156–63.	Level 3b, grade C
	Patterson DR et al. Virtual reality hypnosis: a case report. Int J Clin Exp Hypn 2004;52:27–38.	Level 4, grade C
	Patterson D et al. Hypnosis delivered through immersive virtual reality for burn pain. Int J Clin Exp Hypn 2006;54(2):130–42.	Level 3b, grade B
	Shakibaei F et al. Hypnotherapy in managemnet of pain and reexperiencing of trauma in burn patients. Int J Clin Exp Hypn 2008;56(2):185–97.	Level 1b, grade B
	Van der Does AJ et al. Hypnosis and pain in patients with severe burns: a pilot study. Burns 1988;14(5):399–404. (110)	Level 4, grade C
Distraction techniques/virtual reality	Brown NJ et al. Efficacy of a children's procedural preparation and distraction device on healing in acute burn wound care procedures: study protocol for a randomized controlled trial. Trials 2012;13:238. (135)	Level 5, grade D
	Brown NJ et al. Play and heal: randomized controlled trial of DittoTM intervention efficacy on improving re-epithelialization in pediatric burns. Burns 2014;40(2):204–13. (136)	Level 2b, grade B
	Carrougher GJ et al. The effect of virtual reality on pain and range of motion in adults with burn injuries. J Burn Care Rehabil 2009;30(5):785–91. (126)	Level 1b, grade A
	Chan E et al. Application of a virtual reality prototype for pain relief of pediatric burn in Taiwan. J Clin Nurs 2007;16(4):786–93. (122)	Level 4, grade C
	Das DA et al. The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: a randomized controlled trial. BMC Pediat 1995;5(1):1. (109)	Level 2b, grade B
	Eccleston C, Crombez G. Pain demands attention: a cognitive-affective model of the interruptive function of pain. Psychol Bull 1999;125:356–66. (119)	Level 5, grade D
	Hoffman H et al. Virtual reality pain control during burn wound debridement in the hydrotank. Clin J Pain 2008;24(4):299–304. (125)	Level 3b, grade B
	Hoffman HG et al. Water-friendly virtual reality pain control during wound care. J Clin Psychol 2004;60(2):189–95. (137)	Level 4, grade C
	Hoffman HG et al. Use of virtual reality for adjunctive treatment of adult burn pain during physical therapy: a controlled study. Clin J Pain 2000;16: 244–50. (132)	Level 3b, grade B
	Hoffman HG et al. Virtual reality as an adjunctive pain control during burn wound care in adolescent patients. Pain 2000;85(1–2):305–9. (121)	Level 4, grade C
	Konstantatos AH et al. Predicting the effectiveness of virtual reality relaxation on pain and anxiety when added to PCA morphine in patients having burns dressings changes. Burns 2009;35(4):491–9.	Level 1b, grade A
	Maani C et al. Pain control during wound care for combat-related burn injuries using custom, articulated arm-mounted virtual reality goggles. J Cyberther Rehabil 2008;1(2):193–8. (120)	Level 4, grade C
	Miller AC et al. A distraction technique for control of burn pain. J Burn Care Rehabili 1992;22(2):144–9. (107)	Level 2b, grade B
	Miller K et al. Multi-modal distraction. Using technology to combat pain in young children with burn injuries. Burns 2010;36(5):647–58. (128)	Level 2b, grade B
	Morris LD et al. The effectiveness of virtual reality on reducing pain and anxiety in burn injury patients. Clin J Pain 2009;25(9):815–26. (127)	Level 2a, grade B
	Morris LD et al. Feasibility and potential effect of a low-cost virtual reality system on reducing pain and anxiety in adult burn injury patients during physiotherapy in a developing country. Burns 2010;36(5):659–64. (129)	Level 4, grade C
	Mott J et al. The efficacy of an augmented virtual reality system to alleviate pain in children undergoing burns dressing changes: a randomized controlled trial. Burns 2008;34(6):803–8. (118)	Level 1b, grade A
	Park E et al. The effects of relaxation breathing on procedural pain and anxiety during burn care. Burns 2013;39(6):1101–6.	Level 2c, grade B
	Schmitt YS et al. A randomized, controlled trial of immersive virtual reality analgesia, during physical therapy for pediatric burns. Burns 2011;37(1):61–8. (130)	Level 1b, grade A
	Sharar S et al. Factors influencing the efficacy of virtual reality distraction analgesia during postburn physical therapy: preliminary results from 3 ongoing studies. Arch Phys Med Rehabili 200788(12 Suppl 2):S43–9. (123)	Level 3b, grade B
	Slater M,Wibur S. A framework for immersive virtual environments (FIVE): speculations on the role of presence in virtual environments. Presence 1997;6:603–16. (131)	Level 5, grade D
	Small C et al. Virtual restorative environment therapy as an adjunct to pain control during burn dressing changes: study protocol for a randomized controlled trial. Trials 2015;16:329.	Level 4, grade C
	van Twillert B et al. Computer-generated virtual reality to control pain and anxiety in pediatric and adult burn patients during wound dressing changes. J Burn Care Res 2007;28(5): 694–702. (124)	Level 1b, grade B
Music	Ferguson SL, Voll KV. Burn pain and anxiety: the use of music relaxation during rehabilitation. J Burn Care Rehabili 2004;25(1):8–14.	Level 3b, grade B
	Fratianne RB et al. The effect of music-based imagery and musical alternate engagement on the burn debriedement process. J Burn Care Rehabil 2001;22(1):47–53.	Level 2c, grade B
	Hsu KC et al. Effect of music intervention on burn patients' pain and anxiety during dressing changes. Burns 2016;42(8):1789–96. (133)	Level 2b, grade B
	Presner JD et al. Music therapy for assistance with pain and anxiety management in burn treatment. J Burn Care Rehabil 2001;22(1):83–8.	Level 5, grade D
	Tan X et al. The efficacy of music therapy protocols for decreasing pain, anxiety, and muscle tension levels during burn dressing changes: a prospective randomized crossover trial. J Burn Care Res 2010;31(4):590–7. (134)	Level 2b, grade B
	Whitehead-Pleaux AM et al. The effects of music therapy on pediatric patients' pain and anxiety during donor site dressing change. J Music Ther 2006;43(2):136–53.	Level 2b, grade C
	Whitehead-Pleaux AM et al. Exploring the effects of music therapy on pediatric pain: phase 1. J Music Ther 2007;44(3):217–41.	Level 2c, grade C
Relaxation	Choi J et al. Aromatherapy for the relief of symptoms in burn patients: a systematic review of randomized controlled trials. Burns 2017;44(6):1395–402. (117)	Level 3a, grade B
	Knudson-Cooper MS. Relaxation and biofeedback training in the treatment of severely burned children. J Burn Care Rehabil 1981;2(2):102–110.	Level 2b, grade C
	Wernick RL et al. Pain management in severely burned adults: a test of stress inoculation. J Behav Med 1981;4(1):103–9.	Level 2c, grade C
Massage	Field T et al. Post-burn itching, pain, and psychological symptoms are reduced with massage therapy. J Burn Care Rehabil 2000;21(3):189–93.	Level 2b, grade C
	Field T et al. Burn injuries benefit from massage therapy. J Burn Care Rehabil 1998;19(3):241–4.	Level 2b, grade C
	Hernandez-Reif M et al. Childrens’ distress during burn treatment is reduced by massage therapy. J Burn Care Rehabili 2011;22:191–5. (115)	Level 2b, grade C
	Parlak Gurol A et al. Itching, pain, and anxiety levels are reduced with massage therapy in burned adolescents.” J Burn Care Res 2010;31(3):429–32. (114)	Level 2c, grade B
	Seyyed-Rasooli A et al. Comparing the effects of aromatherapy massage and inhalation aromatherapy on anxiety and pain in burn patients: a single-blind randomized clinical trial. Burns 2016;42(8):1774–80. (116)	Level 1b, grade B

Table 2.

Levels of evidence

1a	Systematic Review of Randomized Control Trials
1b	Individual Randomized Control Trials (with narrow Confidence Interval)
1c	All or none case-series
2a	Systematic review of cohort studies
2b	Individual cohort study (including low quality RCT; eg, <80% follow-up)
2c	Outcomes Research or Ecological studies
3a	Systematic review of case–control studies
3b	Individual Case–control Study
4	Case-series (and poor quality cohort and case–control studies)
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”

STANDARDS

Despite examining 10 additional years of research there are insufficient data to fully support high-level evidence-based standards of care. Nevertheless, we combine the evidence available and expert opinion to put forth several guidelines for the assessment and management of pain during acute burn hospitalization.

Recommendations for the management of acute pain in the adult burn patient (see online long version of the article for detailed explanations of the recommendations; see Table 3 for levels of recommendation).

Table 3.

Grades of recommendations

A	Consistent level 1 studies
B	Consistent level 2 or 3 studies or extrapolations from level 1 studies
C	Level 4 studies or extrapolations from level 2 or 3 studies
D	Level 5 evidence or troublingly inconsistent or inconclusive studies of any level

Pain Assessment

1. Pain assessments should be performed several times a day and during various phases of care (Level A)

2. Pain assessments should be protocolized and recorded by the physician and the nursing staff during the various stages of care to ensure consistent language when discussing pain evaluation (Level B)

3. Pain assessment tools should use patient-reported scales when able (Level C)

4. The Burn Specific Pain Anxiety Scale (BSPAS) should be included as one of the pain assessments used during an acute burn hospitalization as it is a validated tool for the burn patient population and includes evaluation of anxiety (Level C)

5. Critical Care Pain Observation Tool (CPOT) can be used when a patient is not able to interact or communicate their individual assessment of pain (Level D)

Opioid Pain Medications

• 6.When choosing opioid pain medications, decisions about choice of agent should be based on physiology, pharmacology, and physician experience given the limited amount of high-quality data available (Level C)
• 7.Opioid therapy should be individualized to each patient and continuously adjusted throughout their care due to the heterogeneity of individual responses, adverse effects, and the narrow therapeutic window of opioids (Level D)
• 8.Attempts should be made to use as few opiate equivalents as needed to achieve the desired level of pain control (Level C)
• 9.Opioid pain medications should not be used in isolation but in conjunction with nonopioid and nonpharmacological measures (Level C)
• 10.Patients should be educated about the role of opioids and other pain medications in their recovery from burn injury (Level D)

Nonopioid Pain Medications

• 11.Acetaminophen should be utilized on all burn patients, with care taken to monitor the maximal daily dose (Level D)
• 12.Nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered in all patients due to their safety profile and efficacy in other settings; however, the patient’s clinical picture including baseline comorbidities and kidney function as well as surgeon preference should be included in this decision (Level D)
• 13.Agents for the treatment of neuropathic pain (eg, gabapentin or pregabalin) should be considered as an adjunct to an opioid in patients who are having neuropathic pain or who are refractory to standard therapy (Level C)
• 14.Ketamine should be considered for procedural sedation, with appropriate training and monitoring for the physician and nursing staff who are administering (Level B)
• 15.Low-dose ketamine should be considered as an adjunct to opioid therapy in patients who could benefit from reduced opioid consumption, particularly in the postoperative period (Level D)
• 16.Dexmedetomidine and clonidine are recommended as pain management adjuncts, particularly in patients showing signs of withdrawal or prominent anxiety symptoms and dexmedetomidine as a first-line sedative in the intubated burn patient (Level D)
• 17.The use of IV lidocaine for burn pain management cannot be recommended at this time as a first-line agent, but it is a reasonable second- or third-line adjuvant agent (Level D)
• 18.Given the lack of evidence and the potential legal and political obstacles, we are unable to make a recommendation for the use of cannabinoids in the treatment of acute burn pain (Level D)

Regional Anesthesia

• 19.Regional anesthesia for burn pain management has the potential to provide improved pain relief, patient satisfaction, and opioid use reduction without serious risks or complications (Level C)

Nonpharmacologic Treatments

• 20.Every patient should be offered a nonpharmacological pain control technique, at least as an adjunctive measure to their pain control regimen. When the expertise and/or equipment is available, cognitive-behavioral therapy, hypnosis and virtual reality have the strongest evidence. (Level A)

CONCLUSIONS

The management of pain following a burn is extremely complex and the various phases of care must be considered in pain assessments as well as when choosing which treatment modalities to use. All of the various modalities of pain control discussed above have a role in pain control for the burn-injured patient and can be used to create an individualized multimodal pain plan for each patient. While there is increasing research on all of these modalities, the available studies are inadequate to support a true standard of care. Moving forward we call for more burn specific research into all modalities for burn pain control as well as research on multimodal pain control. Additionally, we call for the use of common data elements in burn pain research studies so studies and protocols created can be reliably compared.

Funding: This project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR001860. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of interest statement. No competing financial interests exist.