Paradigm-based treatment approaches for management of burn pain

INTRODUCTION — Pain management is a central component of the treatment of patients with burns. Despite advances in burn care, management of burn pain is often inadequate during the acute and chronic rehabilitation phases of burn care [1]. Pain is among the most common causes of distress during the first year after recovery and, hence, should be aggressively managed [2,3]. Burn pain management is typically based upon clinical experience and clinician and/or institutional preference, since available evidence is insufficient to clearly support one approach [4].

The approach to the management of patients with acute, background, procedural, and chronic pain secondary to burns will be discussed here. An overview of the pharmacologic and nonpharmacologic treatment options for managing burn pain is reviewed elsewhere. (See "Management of burn wound pain and itching".)

BURN PAIN PARADIGM — A burn pain paradigm guides the use of analgesics for management of the different phases and variability of burn pain [5]. This paradigm is based upon five phases of burn pain occurrence and includes:

●Background pain – Pain that is present while the patient is at rest, results from the thermal tissue injury itself, and is typically of low-to-moderate intensity and long duration.

●Procedural pain – Brief but intense pain that is generated by wound debridement and dressing changes and/or rehabilitation activities (eg, physical therapy and occupational therapy).

●Breakthrough pain – Unexpected spiking of pain levels that occurs when current analgesic effects are exceeded, either at rest, during procedures, or with anxiety.

●Postoperative pain – A predictable and temporary increase in pain that occurs after burn excision, donor skin harvesting, and grafting due to the creation of new and painful wounds in the process. The duration of pain is typically two to five days.

●Chronic pain – Pain that lasts longer than three to six months or remains after all burn wounds and skin graft donor sites have healed. The most common form of chronic pain is neuropathic pain, which is the result of damage sustained by the nerve endings in the skin.

CHALLENGES IN MANAGING BURN PAIN — Acute and chronic burn pain is challenging to treat because of multiple components that must be addressed in addition to the changing patterns of pain with time:

●Variability of pain – Burn pain is variable among patients and within each individual. Adequate pain management must be matched with the current situation and be flexible enough to allow for predictable and unpredictable changes. As an example, burn pain can be mild when the burn sites are undisturbed (background pain), become severe with dressing changes and physical therapy (predictable procedural pain), and be interspersed with periods of excruciating pain at unpredictable times (unpredictable breakthrough pain, eg, at night). Psychosocial factors, particularly those relating to the circumstances of a burn injury, may have a significant impact on the individual pain experience.

●Dosing of analgesics – Opioid analgesic dosing in pediatric patients is based on patient weight, which is variable in the burn patient due to physiologic fluid shifts. In adults, opioid response may be variable depending on existing tolerance and may be limited by side effects including respiratory depression, sedation, pruritus, and constipation. (See "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Hypermetabolic response'.)

●Pharmacokinetics – Burn injuries result in variable and often unpredictable changes in volume of distribution and clearance of anesthetics and analgesics, including morphine [6]. In addition, renal and hepatic function may be compromised in patients with burn injuries.

●Route of drug administration – Options include enteral (oral, rectal, gastric via feeding tube), intravenous, inhalational, transmucosal, transdermal, intramuscular, and perineural. The enteral route is generally preferred for management of background pain and in the outpatient setting. The intravenous route generally provides rapid onset but shorter duration of pain relief and is used for severe background pain, procedural/postoperative pain, or breakthrough pain; monitoring of vital signs is mandatory when intravenous opioids are used.

Transmucosal immediate-release fentanyl has been used for the management of procedural pain in burns patients. However, it is approved for use in the United States only for breakthrough pain in opioid tolerant patients with cancer; we no longer use it for breakthrough pain in our burn center. Transmucosal buprenorphine is used for background pain in patients with substance use disorder or in those who are sensitive to full agonists (eg, older adults). Regional anesthesia is useful for inpatients [7].

●Opioid tolerance – Tolerance to analgesic effects generally occurs after more than two weeks of opioid use. The frequency of opioid tolerance has not been objectively documented in burn patients, but clinical experience is that the majority of burn patients receiving opioids on a daily basis develop analgesic tolerance during the initial weeks of treatment [5], possibly due to pharmacodynamic changes at the opioid receptor [8]. Over time, a higher dose of medication is needed to achieve the same level of pain relief.

●Hyperalgesia – Hyperalgesia is an increased sensitivity to pain and is induced by the acute inflammatory response of a burn injury. Primary hyperalgesia occurs in the tissues directly damaged by the burn. Secondary hyperalgesia occurs in the normal tissues adjacent to the burn. Continued or repeated painful stimuli associated with background pain or repeated procedural pain can cause central nervous system sensitization that amplifies the pain experience via hyperexcitability of pain pathways [9]. Such pain may be opioid resistant and become irreversible and thus contribute to ineffective opioid analgesia [10]. Patients with a history of opioid use may experience hyperalgesia, and the pain management protocol will need to be adjusted accordingly. Opioid-induced hyperalgesia is a form of hyperalgesia caused by exposure to opioids, meaning patients receiving these drugs paradoxically become more sensitive to painful stimuli [11].

DRUGS AND DOSING — Drug options and dosing for opioids, nonopioids, benzodiazepines, and adjuvant analgesics are provided separately. (See "Pain control in the critically ill adult patient" and "Approach to the management of acute pain in adults" and "Pharmacologic management of chronic non-cancer pain in adults".)

Optimizing pharmacotherapy — The principles for optimizing opioid pharmacotherapy in burn patients are [4]:

●Treat burn pain based upon the five components of the burn pain paradigm: background, procedural, breakthrough, postoperative, and chronic. (See 'Burn pain paradigm' above.)

●Individualize doses, set a flexible dosing schedule, and use frequent dose adjustments as needed to account for variability in analgesic requirements.

●Assess and document the effectiveness of the pain regimen at regular intervals to adjust doses and dosing intervals. Assessment should use a validated, reproducible tool to measure pain intensity at rest and during movement. Tools are available for children as well as cognitively impaired adults. Additionally, assessment of pain management should focus more on comfort, function, and sleep rather than unidimensional pain scores [12].

●Monitor side effects of analgesia and take steps to prevent or treat them rather than undertreating pain. Common examples include treating epidural-induced hypotension, or switching from morphine to oxycodone in order to mitigate nausea.

●Use nonopioid drugs in conjunction with opioids to enhance analgesia and reduce risks of opioid side effects. (See "Management of burn wound pain and itching", section on 'Pharmacologic treatment options'.)

●Monitor anxiety and changes in mood and consider early psychological support or an anxiolytic for procedures, if indicated.

●Apply nonpharmacologic interventions to complement, not replace, systemic analgesia. (See "Management of burn wound pain and itching", section on 'Nonpharmacologic treatment options'.)

PARADIGM-BASED MANAGEMENT — We, and many other burn centers, advocate a structured approach to analgesia that incorporates both pharmacologic and nonpharmacologic therapies, targets the specific clinical pain settings unique to the burn patient, and is individualized to meet specific patient needs and institutional capabilities [13-15]. The sections below provide an approach to treatment of burn pain based upon the five phases of the burn pain paradigm.

Selection of an analgesic regimen is based upon the clinical setting, the effectiveness of the approach in alleviating pain and improving function, and clinician and institutional preferences. No regimen is appropriate in all settings, and there is no high-quality evidence that any particular regimen is more effective than another. (See "Management of burn wound pain and itching", section on 'Pharmacologic treatment options' and "Management of burn wound pain and itching", section on 'Nonpharmacologic treatment options'.)

In pediatric patients, in whom risks from analgesia and clinical unfamiliarity are elevated, the use of a weight-based medication worksheet (placed at the bedside and in the patient record) containing all analgesic and resuscitation drugs provides a supplemental safeguard against accidental overdose [16].

Background pain — Background pain is expected to decrease with time as the burn wound and associated donor skin graft sites heal. Titrating pain management to functional status is vital, and along with regular assessment of pain, it is important to ask about activity level and sleep. Analgesia can be tapered as the pain lessens in severity and frequency. The optimal treatment of background pain relies on regular or scheduled multimodal analgesia in order to maintain stable plasma drug concentrations and to mitigate side effects of any one agent [5].

●Pharmacologic approaches (see "Management of burn wound pain and itching", section on 'Pharmacologic treatment options'):

•Oral administration on a regular schedule of nonsteroidal anti-inflammatory agents (NSAIDs) and acetaminophen.

•Intravenous (IV) opioid administration, such as patient-controlled analgesia (PCA). This may be appropriate earlier on following a burn injury when opioid requirements are usually higher or where the enteral route is unavailable.

•Oral administration of immediate release opioids on a regular, "as required" schedule. A number of burns centers have traditionally used long-acting opioids such as methadone for background pain as it is a long-acting agent with N-Methyl-D-Aspartate (NMDA) receptor antagonist properties. However, there appears to be an association between the use of long-acting opioids and an increased risk of progression to long-term opioid use [17]. While methadone is still used for acute pain in our burns center, its use has decreased, and patients who are put on it are monitored closely.

●Nonpharmacologic approaches (see "Management of burn wound pain and itching", section on 'Nonpharmacologic treatment options'):

•Relaxation techniques including meditation, progressive muscle relaxation, deep breathing, and guided imagery

•Hypnosis

•Information provision

•Cognitive restructuring

•Enhanced coping skills

•Positioning patients for comfort and to account for areas of hyperalgesia or allodynia

Breakthrough pain — Breakthrough pain occurs when the comfort provided by background pain management is exceeded and may manifest as sudden, more intense spikes of pain [18]. Breakthrough pain can result from an increase in activity level, development of opioid tolerance, and/or changes in the burn wound that increase pain (eg, proliferation of epidermal skin buds during the spontaneous burn healing process, burn wound infection). Adjustments to the pharmacologic and/or nonpharmacologic pain management should be made after a thorough history and examination to determine the most likely cause. Questions about the site, timing, severity, and character of the pain, as well as exacerbating and alleviating factors, can aid management strategies. As an example, pain related to increased activity level may be managed by timing an extra dose of analgesia and by educating the patient about pacing themselves to avoid under- and overactivity. Opioid tolerance may be managed by a change in agent, often referred to as opioid rotation [19]. New pathology, such as wound infection, may warrant a brief increase in opioid dosing and/or addition of new analgesic modalities such as NSAIDs for inflammatory pain or gabapentinoids for neuropathic pain [20].

Postoperative pain — Increased nociceptive pain following surgery may require a short-term (approximately one to four days) increase in background opioid analgesic administration or even a switch to IV PCA. Other strategies include the use of continuous regional block techniques, IV lidocaine infusions, and 24- to 48-hour low-dose ketamine infusions [7,21-23]. (See "Approach to the management of acute pain in adults".)

Procedural pain — Anticipatory anxiety is an important issue that can develop with the repeated performance of wound care. When adequate analgesia is not provided for an initial, painful procedure, the effectiveness of analgesia for subsequent procedures is reduced, in large part due to anticipatory anxiety and heightened arousal [24,25]. Thus, efforts to provide effective procedural burn pain management should begin with the first wound care procedure.

Dressing changes produce pain that is more intense and shorter in duration than background pain and are optimally managed using a combination of sedatives, analgesics, and anxiolytics [26]. Sedation should be considered as a continuum from mild (anxiolytic only with no change in cognitive response) to moderate (depressed consciousness but responds purposely to verbal or tactile stimulation) to deep (hard to rouse, responds purposely to intense, painful stimulation) to full general anesthesia (no response attainable to stimulation). Administration of moderate or deep sedation should follow institutional guidelines developed for safety and efficacy. Such guidelines have been established by the American Society of Anesthesiologists [27] and adopted by the Joint Commission on Accreditation of Healthcare Organizations [28]. These guidelines dictate the safety monitoring requirements and specific agents that can be used for procedural analgesia, as some of the more potent opioids (eg, remifentanil) or anesthetics (eg, ketamine) may result in excessive sedation. Deep sedation and general anesthesia warrant a qualified anesthesia provider being present to administer sedative agents and safely monitor the patient. This type of sedation requires an operating room environment and is not suitable for bedside care in a ward.

Patient requirements for sedation and analgesia during dressing changes should therefore be reviewed regularly and stepped down appropriately. Full use of multimodal analgesic strategies, including nerve blocks, should be considered in order to reduce sedative requirements. Nonpharmacologic techniques (eg, information provision, distraction, relaxation) serve as an essential adjunct to pharmacologic management [29].

Pharmacologic approaches — Typical pharmacologic analgesic regimens for procedural care include opioids, benzodiazepines, and low doses of anesthetic agents such as nitrous oxide and ketamine. Any drugs used should ideally have a rapid onset and short duration of action.

Local anesthetic placed to reduce sensation to a limb or area of the trunk has an important role in managing procedural pain. Local anesthetic can be placed as a single shot to last from 12 to 24 hours, or a catheter can be placed to allow for a continuous infusion of anesthetic for several days. Placement usually requires the use of ultrasound by an anesthesia provider experienced in regional anesthetic techniques [7].

When administered by appropriately trained and experienced personnel (eg, anesthesia providers), propofol is a safe and effective alternative for managing procedural pain [30,31]. Propofol is particularly advantageous as it can be titrated to effect both in terms of level of consciousness and duration of action using continuous IV infusion techniques and has the additional benefit of a rapid awakening with a minimal risk of nausea. However, propofol is more rapidly cleared and has a higher volume of distribution in burn patients, necessitating careful increases in dose [32,33].

The following illustrate the pharmacologic approaches to procedural pain, based upon anticipated severity of pain:

●Minor procedure pain – Minor procedures may require analgesia and/or sedation, particularly for children. These procedures include removal of numerous staples from grafted sites, meticulous wound care of recently grafted sites and/or donor sites, and wound care involving the face and/or neck. A well-timed dose of oral analgesia (eg, oxycodone given 20 to 30 minutes prior) with or without IV boluses titrated during the procedure may provide adequate analgesia. Oral or intranasal ketamine is an option for pediatric burn patients without IV access [34,35]. However, ketamine use is limited by the potential risk of associated emergence delirium reactions (5 to 30 percent incidence), particularly in older adults. Intranasal dexmedetomidine has been used in pediatric patients [36].

●Mild-to-moderate procedural pain – IV and inhalation medications have a rapid onset of action and a short duration of activity, while oral agents have a prolonged onset of action and duration. Inhalation anesthetics can be used if IV access is not possible. The following oral, IV, and inhaled analgesics are used to control mild-to-moderate procedural pain [34,37-42]:

•Nonopioid analgesics, anti-inflammatory agents (eg, acetaminophen, ibuprofen)

•IV opioid analgesics (eg, fentanyl, remifentanil, hydromorphone)

•IV anesthetic agents (eg, propofol, ketamine, dexmedetomidine, lidocaine)

•Orally administered opioid analgesics (eg, oxycodone, hydromorphone)

•Oral ketamine

•Oral clonidine

•Inhaled nitrous oxide

●Severe procedural pain – General anesthesia, deep sedation, or regional anesthesia is useful for severely painful dressing changes or ones that require extreme cooperation in a noncompliant patient (eg, face debridement in a young child) [43,44].

Nonpharmacologic approaches — Nonpharmacologic approaches have included the following

●Relaxation techniques including meditation, progressive muscle relaxation, deep breathing, and guided imagery

●Hypnosis

●Distraction – media (iPad games, videos, etc.), bubbles, songs, virtual reality [45]

●Information provision

●Cognitive restructuring

●Enhanced coping skills

One of the most useful nonpharmacologic analgesic techniques in this setting is information provision, so that patients understand and anticipate both the increase and temporary nature of the postoperative pain. (See "Management of burn wound pain and itching", section on 'Information provision'.)

Chronic pain — Pain is considered chronic if it exists between three to six months after the wound has healed. Chronic pain is associated with a reduction in quality of life. The study of chronic pain and hyperalgesia in the burn patient population is in the early stages of investigation, and the pathophysiology remains poorly understood [46]. Retrospective reviews found that 33 to 50 percent of burn patients have chronic pain that persists for years after the burns are healed [47-50].

The most common form of chronic pain is neuropathic pain. Neuropathic pain is the result of damage sustained by the nerve endings in the skin. Other causes of chronic pain are likely from musculoskeletal pain associated with deconditioning. Patients report that chronic pain is exacerbated by temperature change, dependent position, or weight-bearing activities. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Pharmacologic therapy for neuropathic pain, or nociplastic or centralized pain'.)

No data from randomized trials have identified the optimal management of chronic pain in burn patients. Chronic pain is best managed with nonopioid analgesics and nonpharmacologic approaches. Extreme caution should be taken if opioids are to be used for chronic pain, with careful supervision for safety and adjustments of the doses and dosing schedule based upon response. Medication options for chronic neuropathic pain include pregabalin [51], gabapentin [52], and duloxetine [53]. NSAIDs may also be an effective nonopioid analgesic. (See "NSAIDs: Therapeutic use and variability of response in adults".)

Nonpharmacologic approaches should focus on the impact of chronic pain. These approaches include cognitive behavioral strategies, such as distraction techniques, relaxation, and mindfulness-based stress reduction that can target healthy lifestyle choices and adaptive thinking styles. (See "Management of burn wound pain and itching", section on 'Nonpharmacologic treatment options'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic pain management" and "Society guideline links: Acute pain management".)

SUMMARY AND RECOMMENDATIONS — Pain management is a central component of the treatment of patients with burns. Despite advances in various aspects of burn care, control of burn pain is often inadequate during the acute and chronic rehabilitation phases of burn care. Pain is among the most common causes of distress during the first year after recovery and, hence, should be aggressively managed.

●Burn pain management – Optimal management of burn pain requires a structured approach that incorporates both pharmacologic and nonpharmacologic therapies, targets the specific clinical pain settings unique to the burn patient, and is individualized to meet specific patient needs and institutional capabilities. A burn pain paradigm can be used to guide management of the different phases and variability of burn pain. This paradigm is based upon five phases of burn pain occurrence: background, procedural, breakthrough, postoperative, and chronic pain. (See 'Challenges in managing burn pain' above and 'Burn pain paradigm' above and 'Paradigm-based management' above.)

•Background pain and breakthrough pain – For background pain management, the combination of pharmacologic and nonpharmacologic techniques can be used. We suggest using a multimodal approach to analgesic drug therapy as detailed above. Frequent reevaluation of drug therapy to monitor for efficacy, side effects, and tolerance is recommended. When pain exceeds background pain management adjustments to the pharmacologic and/or nonpharmacologic pain management should be made after a thorough history and examination to determine the most likely cause. (See 'Background pain' above and 'Breakthrough pain' above.)

•Procedural pain – For procedural pain management (eg, dressing changes), the combination of pharmacologic and nonpharmacologic techniques can be used. The approach depends on the anticipated pain caused by the procedure. For procedures that are severely painful, we suggest general or regional anesthesia (Grade 2B). For mildly-to-moderately painful procedures, a combination of analgesic and anxiolytic drugs with rapid onset and short duration along with nonpharmacologic techniques (eg, hypnosis, information provision) may be sufficient (table 1). For procedures that cause minor pain, mild pharmacologic sedation with nonpharmacologic approaches will usually suffice. (See 'Procedural pain' above.)

•Postoperative pain – For postoperative pain management, a transient increase in dosing of opioids and the use of regional anesthetics can be added as needed. We suggest using intravenous (IV) hydromorphone or fentanyl for the critical care setting (Grade 2B). For noncritical care settings, and when IV access is not available, postoperative pain can be managed with oxycodone. Nonpharmacologic techniques that were effective prior to the operation and that matched a person's coping style should continue to be used in the postoperative period. A particularly helpful technique is information provision. (See 'Postoperative pain' above.)

•Chronic pain – For chronic and neuropathic pain management, the combination of pharmacologic and nonpharmacologic techniques may be useful in managing pain. We suggest nonopioid regimens, with adjustments of the doses and dosing schedule based upon response (Grade 2B). Nonpharmacologic options, such as cognitive distraction, mindfulness-based stress reduction, hypnosis, and relaxation techniques, should focus on decreasing the impact of chronic pain and enhancing quality of life. (See 'Chronic pain' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Sam R Sharar, MD, who contributed to an earlier version of this topic review.