Paradigm-based treatment approaches for burn pain control

Authors:
Shelley Wiechman, PhD
Sam R Sharar, MD
Section Editor:
Marc G Jeschke, MD, PhD
Deputy Editor:
Kathryn A Collins, MD, PhD, FACS
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2018. | This topic last updated: Aug 23, 2018.

INTRODUCTION — Pain management is a central component of the treatment of patients with burns. Despite advances in burn care, control 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 physician 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 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 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 and 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 directed toward the current situation. As an example, burn pain can be excruciating with dressing changes and physical
therapy but less painful when the burn sites are undisturbed (background pain).

●Dosing of analgesics – Opioid analgesic dosing is based on patient weight, which is variable in the burn patient due to physiologic fluid shifts. (See "Hypermetabolic response to severe burn injury", 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].

●Route of drug administration – Options include intravenous, inhalation, oral, transmucosal, enteral tube, or rectal. The intravenous route provides rapid onset and short duration of pain relief and is used for patients with moderate-to-severe burns,
and monitoring of vital signs is mandatory. Oral administration is ideal for the outpatient setting.

●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 [7]. 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 adaptations that amplify the pain experience (ie, windup). Such pain may be
opioid resistant and become irreversible and thus contribute to ineffective opioid analgesia [8].

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

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 dosage, 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 dosages and dosing intervals.
 ●Monitor side effects and prevent or treat them; do not undermedicate.

●Consider using nonopioids in conjunction with potent 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.

●Apply nonpharmacologic interventions to complement, not replace, 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 [9,10]. The sections below provide an approach to treatment of burn pain based upon the five phases of the burn pain paradigm. The regimens used at our institution
are illustrated in the table (table 1).

Selection of an analgesic regimen is based upon the clinical setting, the effectiveness of the approach in alleviating pain, 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 addition, the regular 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 in pediatric patients. This
is particularly important in the young pediatric age group, where risks from analgesia and clinical unfamiliarity are both elevated [11].

Background pain — Pharmacologic and nonpharmacologic management strategies relieve background pain. Background pain decreases with time as the burn wound and associated donor skin graft sites heal, and analgesics can be slowly tapered as
the pain lessens in severity and frequency. The optimal treatment of background pain is mildly to moderately potent analgesics administered so that plasma drug concentrations remain relatively constant [5].

Pharmacologic approaches:

●Continuous intravenous (IV) opioid infusions, such as patient-controlled analgesia (PCA)

●Oral administration of long-acting opioids with prolonged elimination (methadone) or prolonged enteral absorption (sustained-release morphine)

●Oral administration on a regular schedule of short-acting oral opioid analgesics or nonsteroidal anti-inflammatory agents (NSAIDs)

(See "Management of burn wound pain and itching", section on 'Pharmacologic treatment options'.)

Nonpharmacologic approaches:
 ●Relaxation techniques including meditation, progressive muscle relaxation, and guided imagery

●Hypnosis

●Information provision

●Enhanced coping skills

(See "Management of burn wound pain and itching", section on 'Nonpharmacologic treatment options'.)

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 [12,13]. 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 potent sedation, analgesia, anxiolytics, and/or general anesthesia [14]. However, it is impractical to use general
anesthesia on a daily basis. Nonetheless, the provision of deep sedation with carefully titrated inhaled or IV anesthetic agents, brief general anesthetics, and regional analgesic techniques can have a role in procedural burn pain settings.
Nonpharmacologic techniques (eg, information provision, distraction, relaxation) serve as an adjunct to pharmacologic management.

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 (ASA) [15] and adopted by the Joint Commission on
Accreditation of Healthcare Organizations (JCAHO) [16]. 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.

Typical pharmacologic analgesic regimens include moderately to highly potent opioids with a short duration of action, often in combination with anxiolytics (eg, benzodiazepines). However, nonopioid agents such as ketamine are used in some centers,
particularly in children. The use of potent opioid analgesics and anxiolytics can occur in settings with or without intravenous access, yet always requires adequate monitoring, personnel, and resuscitation equipment. For most burn wound debridement
procedures, opioid analgesia with or without the concurrent use of anxiolytic sedatives (eg, benzodiazepines) will often produce mild-to-moderate sedation.

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

●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) [17,18].

●Mild-to-moderate procedural pain – Intravenous 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
intravenous (IV) access is not possible. The following oral, IV, and inhaled analgesics are used to control mild-to-moderate procedural pain [19-25]:
 •Nonopioid analgesics, anti-inflammatory agents (eg, acetaminophen, ibuprofen)

•IV opioid analgesics (eg, fentanyl, remifentanil)

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

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

•Oral ketamine

•Oral transmucosal fentanyl

•Inhaled nitrous oxide

●Minor procedure pain – Minor procedures may also 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/ordonor
sites, and wound care involving the face and/or neck. Either ketamine or propofol can be used for minor procedures, depending on the surgeon's preference. Historically, IV or intramuscular ketamine has been used in children and adults [26,27].

•Oral ketamine is an option for pediatric burn patients without IV access [19]. However, ketamine use is limited by the potential risk of associated emergence delirium reactions (5 to 30 percent incidence), particularly in older adults.

•When administered by appropriately trained and experienced personnel (eg, anesthesia providers), propofol is a safe and effective alternative in the burn pain management setting [28] and is being evaluated as a potential drug for PCA delivery
for less aggressive wound care procedures [29]. 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 [30,31].

Nonpharmacologic approaches:

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

●Hypnosis

●Distraction – media (iPad games, videos, etc.), bubbles, songs

●Information provision
 ●Enhanced coping skills

Breakthrough pain — Breakthrough pain occurs when the comfort provided by background pain management is exceeded [32]. The cause of breakthrough pain includes inadequate background analgesic management, 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). A change in the pharmacologic and/or nonpharmacologic pain management is
based upon the correct diagnosis for the breakthrough pain. As an example, an adult patient hospitalized with a partial-thickness burn covering 10 percent total body surface area is receiving 10 mg oral methadone every 12 hours for background pain. After
one week, as painful new skin buds start to appear, the patient consistently requests (and receives) 1 to 2 doses of 10 mg oral oxycodone between methadone administration times. After confirming that the burn wound is not infected, the oral methadone
should be temporarily increased to 15 mg every 12 hours until epidermal coverage is complete.

Postoperative pain — Pharmacologic management of postoperative pain includes a temporary (approximately one to four days) increase in background opioid analgesic support. The optimal management includes the use of continuous regional block
techniques and additional opioid dosing [33]. (See "Management of acute perioperative pain".)

One of the most useful nonpharmacologic analgesic techniques in this setting is information provision, so that patients 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 — The study of chronic pain and hyperalgesia in the burn patient population is in the early stages of investigation, as most of the research has focused on acute pain. Retrospective reviews found that 33 to 50 percent of burn patients have
chronic pain that persists for years after the burns are healed [34-36].

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 "Overview of the treatment of chronic non-cancer pain", section on 'Neuropathic pain'.)

No data from randomized trials have identified the optimal management of chronic pain in burn patients. Chronic pain, like acute pain, is best managed with opioid and nonopioid analgesics, with adjustments of the doses and dosing schedule based upon
response. Medication options also include pregabalin [37] and gabapentin [38]. Nonsteroidal anti-inflammatory drugs (NSAIDs) can also be used as a nonopioid option. (See "NSAIDs: Therapeutic use and variability of response in adults".)

For patients who do not have relief of chronic pain or hyperalgesia with opioids and nonsteroidal anti-inflammatory agents, clinical experience and case studies have shown efficacy with antidepressants (eg, duloxetine) and/or anticonvulsant analgesics
(eg, gabapentin) following burn injuries [38-40]. (See "Overview of the treatment of chronic non-cancer pain", section on 'Anticonvulsants' and "Overview of the treatment of chronic non-cancer pain", section on 'Antidepressants'.)

Nonpharmacologic approaches should focus on the impact of chronic pain. These approaches include diversion techniques and relaxation techniques and can target healthy lifestyle choices and more adaptive thinking styles. (See "Management of burn
wound pain and itching", section on 'Nonpharmacologic treatment options'.)

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.
 ●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. (See 'Paradigm-based management' above.)

●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.
(See 'Burn pain paradigm' above.)

●For background pain management, the combination of pharmacologic and nonpharmacologic techniques can be used. We suggest using continuous or scheduled intravenous morphine for pain management in the critical care setting (Grade 2B).
For patients who are tolerating oral intake, the regimen can be adjusted to include scheduled methadone, extended release morphine, and eventually nonsteroidal anti-inflammatory drugs (NSAIDs)/acetaminophen. (See 'Background pain' above.)

●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 drug with rapid onset and short duration in combination with a nonpharmacologic technique (eg, information provision) may be sufficient.
Appropriate regimens are shown in the table (table 1). For procedures that cause minor pain, mild pharmacologic sedation with nonpharmacologic approaches will usually suffice. (See 'Procedural pain' above.)

●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 morphine or fentanyl for the critical care setting (Grade 2B). For noncritical
care settings, when intravenous (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.)

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

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Topic 16505 Version 12.0

GRAPHICS

University of Washington Burn Center Pain Medication Guidelines

Critical care treatment (without Non-critical care treatment (large open Non-critical care treatment (small open
Critical care treatment (with oral intake)
oral intake) areas) areas/predischarge)

Background pain Continuous morphine sulfate (IV) drip or Scheduled methadone or extended-release morphine or PCA Scheduled methadone or extended-release morphine or Scheduled NSAIDs/acetaminophen, oxycodone or
scheduled doses or PCA PCA none

Procedural pain General or regional anesthesia or deep Oxycodone, fentanyl IV, or oral transmucosal fentanyl or ketamine Oxycodone, fentanyl (IV), nitrous oxide (IH), or oral Oxycodone or ketamine or propofol
sedation for severe pain transmucosal fentanyl or ketamine or propofol
Morphine sulfate (IV), fentanyl (IV), ketamine
and dexmedetomidine (IV)

Breakthrough pain Morphine sulfate (IV) or fentanyl (IV) Oxycodone Oxycodone NSAIDs/acetaminophen or oxycodone

Postoperative pain Continuous morphine sulfate (IV) drip or Scheduled methadone or extended-release morphine or PCA Scheduled methadone or extended-release morphine or Scheduled NSAIDs/acetaminophen, oxycodone or
scheduled doses or PCA PCA none

Chronic pain Gabapentin or other nonopiods or antidepressants Gabapentin or anxiolysis or NSAIDS or

antidepressants

Anxiolysis medications for background

and/or procedure management

Background anxiolysis Scheduled lorazepam (IV) or continuous Scheduled lorazepam None or scheduled lorazepam None
 lorazepam (IV) drip

Procedural anxiolysis Lorazepam or midazolam (IV) Lorazepam None or lorazepam None

Post-hospitalization pain control

Discharge or transfer pain medications N/A For transfer to non-critical care treatment: wean drips; establish PO pain Oxycodone for procedural pain; methadone taper or Oxycodone or NSAIDs for procedural pain
medication early; anticipate dose tapering as needs decrease extended-release morphine; taper if applicable

Representative pain and sedation management guideline for adult (nonpediatric, nongeriatric) burn patients from the University of Washington Burn Center. General medication recommendations are provided for specific pain and anxiolysis needs encountered in various
intensive care units and ward-care settings. Medication options are intentionally limited (for simplicity) and do not include specific dose recommendations (to allow for individual patient variability). Complex or refractory cases are managed through special consultation with
the burn care team and/or pain specialists.

PCA: patient-controlled analgesia; IV: intravenously; NSAIDs: nonsteroidal antiinflammatory drugs; IH: inhalation.
Graphic 59472 Version 6.0

Contributor Disclosures
Shelley Wiechman, PhDNothing to discloseSam R Sharar, MDNothing to discloseMarc G Jeschke, MD, PhDNothing to discloseKathryn A Collins, MD, PhD, FACSNothing to disclose

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