Pain management in acute burns

Overview

Burn pain is uniquely challenging: it is severe, prolonged, and multidimensional, encompassing background pain from the wound itself, procedural pain during dressing changes and rehabilitation, breakthrough episodes, and chronic neuropathic pain that can persist long after wound closure ^[1]. Burn treatments themselves often inflict more pain than the initial injury, making anticipation and pre-treatment of procedural pain a clinical duty ^[1]. These four pain components vary independently across the phases of burn care, requiring continuous reassessment and adjustment of the analgesic strategy ^[13].

Effective burn pain management rests on multimodal analgesia: combining opioids with non-opioid adjuncts (NSAIDs, acetaminophen, ketamine, gabapentinoids), regional techniques, anxiolytics, and nonpharmacologic interventions ^[1][13]. No single agent or technique is sufficient. Burn-specific alterations in pharmacokinetics further complicate dosing, as expanded volume of distribution, hypoalbuminemia, and augmented renal clearance change the behavior of nearly every analgesic drug class ^[15].

Undertreated pain has downstream consequences including impaired wound healing, post-traumatic stress disorder, and chronic pain syndromes. Only 11% of burn inpatients report having received enough pain information, compared to 50% of outpatients ^[4].

Classification

Burn pain has four recognized components:

• Background pain: Continuous pain from the wound at rest.
• Procedural pain: Pain during dressing changes, wound care, debridement, and rehabilitation.
• Breakthrough pain: Episodic exacerbations superimposed on background pain.
• Neuropathic pain: Chronic pain from nerve damage that can persist long after wound closure ^[9].

Pain management must address each component across different phases of burn injury, accounting for burn-induced alterations in pharmacokinetics ^[1][13].

Altered Pharmacokinetics in Burns

Major burn injury produces physiologic changes that alter the pharmacokinetics of virtually every analgesic class. Understanding these mechanisms is essential for effective dosing ^[15][16].

Hypoalbuminemia. Serum albumin falls rapidly after major burns due to capillary leak, dilutional effects of resuscitation, and decreased hepatic synthesis. Drugs that are highly protein-bound to albumin (diazepam, phenytoin, many NSAIDs) have an increased free fraction, resulting in greater pharmacologic effect per dose and higher apparent volume of distribution ^[15].

Increased alpha-1 acid glycoprotein (AAG). AAG is an acute-phase reactant that rises after burn injury. Drugs primarily bound to AAG (fentanyl, methadone, lidocaine) have a decreased free fraction, potentially requiring higher doses to achieve therapeutic effect ^[15].

Expanded volume of distribution (Vd). Aggressive fluid resuscitation, capillary leak, and third-spacing expand the Vd for hydrophilic drugs. Loading doses may need to be increased to achieve target plasma concentrations ^[15][16].

Augmented renal clearance. Hyperdynamic circulation after major burns increases glomerular filtration rate, accelerating the clearance of renally eliminated drugs. Morphine glucuronides, gabapentin, and many antibiotics are affected ^[15].

Hepatic blood flow changes. The hyperdynamic state increases hepatic blood flow, potentially increasing the clearance of drugs with high hepatic extraction ratios (fentanyl, morphine, ketamine) ^[15].

These alterations are dynamic: they evolve across the phases of burn care and vary with burn size, fluid status, and recovery trajectory. Frequent reassessment and dose adjustment are required rather than adherence to fixed protocols ^[13][15].

Pharmacologic Management

Opioids

Opioids remain the cornerstone of burn pain management for both background and procedural pain ^[1][13]. The principal agents include:

Morphine is the most widely used opioid in burn care. It is hydrophilic, with an expanded Vd after major burns, and its active metabolite (morphine-6-glucuronide) accumulates with renal impairment. Continuous infusions provide stable background analgesia; patient-controlled analgesia (PCA) allows patient-driven titration for background pain with demand dosing for breakthrough episodes ^[13][16].

Hydromorphone is approximately 5-7 times more potent than morphine, with less histamine release. It is preferred when morphine produces excessive pruritus or when dose escalation is needed for procedural pain ^[13].

Fentanyl is highly lipophilic with rapid onset, making it useful for procedural pain. Because it is bound primarily to AAG (which rises in burn patients), fentanyl may require higher doses than expected in the postacute phase. Its short duration makes it less suitable for continuous background analgesia without infusion ^[13][15].

Methadone has theoretical advantages for chronic burn pain due to its dual mechanism: mu-opioid receptor agonism and NMDA receptor antagonism, which may counteract central sensitization and opioid-induced hyperalgesia ^[21]. Its long and variable half-life (8-59 hours), complex CYP2B6-dependent metabolism, and QTc prolongation risk require experienced prescribers ^[21]. Methadone lacks burn-specific dosing studies but is increasingly used in burn centers for patients with escalating opioid requirements or neuropathic pain components.

Dosing principles. Background pain should be treated with scheduled long-acting opioids or continuous infusions. Procedural pain requires additional short-acting opioids timed to peak effect before the procedure. Equianalgesic conversion requires awareness of altered pharmacokinetics in burns: augmented renal clearance accelerates morphine elimination, while elevated AAG may blunt fentanyl's free fraction ^[13][15]. Opioid-induced hyperalgesia should be suspected when escalating doses produce paradoxically increasing pain, particularly in patients on prolonged high-dose infusions ^[13].

Non-Opioid Analgesics

Acetaminophen is the foundation of multimodal analgesia. Scheduled dosing (oral 1g every 6 hours or IV 1g every 6 hours in adults) provides baseline analgesia and reduces opioid requirements ^[16]. IV acetaminophen offers reliable bioavailability when enteral access is limited or absorption uncertain. Hepatic considerations are important in burn patients: transaminase elevations are common after major burns, and the total daily dose should not exceed 3g in patients with hepatic compromise ^[13].

NSAIDs. Ibuprofen and ketorolac provide effective anti-inflammatory analgesia and are particularly useful for donor site pain and musculoskeletal pain during rehabilitation. The historical concern that NSAIDs increase surgical bleeding risk in burn patients has limited their perioperative use. Manasyan et al. evaluated scheduled ibuprofen in 53 burn patients undergoing skin grafting and found no association with elevated bleeding risk (perioperative transfusion: 3.2 vs 4.6 units pRBCs, P = .207), no increase in skin graft failure, and no difference in hematoma, seroma, or infection rates ^[14]. These findings suggest that withholding ibuprofen from burn surgery patients based on bleeding concerns alone is not supported by available evidence. Ketorolac (15-30 mg IV every 6 hours) is useful for short-term perioperative analgesia but should be limited to 5 days due to renal and GI risks ^[16]. NSAIDs should be used cautiously in patients with renal impairment, coagulopathy, or active GI pathology.

Ketamine

Ketamine is a dissociative anesthetic with analgesic properties at sub-dissociative doses, making it uniquely versatile for burn pain management ^[16][17][18].

Sub-dissociative dosing (0.1-0.3 mg/kg IV) provides analgesia through NMDA receptor antagonism without loss of consciousness. At these doses, ketamine reduces opioid requirements, may attenuate opioid-induced hyperalgesia, and provides some anxiolysis ^[13][16].

Dissociative dosing (1-2 mg/kg IV) produces profound analgesia and amnesia suitable for painful procedures. Brennan et al. studied 50 IV ketamine cases for burn wound care (median dose 1.2 mg/kg) and found that opioids were needed in only 26% of cases, 92% of patients denied unpleasant recall, and dysphoric reactions occurred in only 6% ^[17]. Cardiopulmonary complications were absent.

Oral ketamine is an emerging option for burn dressing changes. Lintner et al. found that oral ketamine (median 2.5 mg/kg) significantly decreased opioid requirements compared to dressing changes without ketamine (50 vs 75 mg IV morphine equivalents, P = .0097) and improved patient satisfaction ^[18].

Ketamine maintains spontaneous ventilation, which is particularly valuable during dressing changes performed outside the operating room where airway management resources may be limited ^[16]. Co-administration of a benzodiazepine (midazolam 0.5-2 mg IV) is standard practice to reduce emergence dysphoria.

Gabapentinoids

Gabapentin and pregabalin are first-line pharmacologic agents for neuropathic burn pain and post-burn pruritus ^[19]. Both bind the alpha-2-delta subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release. Post-burn neuropathic pain and pruritus share underlying mechanisms of peripheral and central sensitization, and both respond to gabapentinoids when conventional treatments are inadequate ^[19].

Gabapentin is typically started at 100-300 mg three times daily and titrated to effect (usual range 900-3600 mg/day). It is renally cleared, requiring dose adjustment in patients with renal impairment or augmented renal clearance ^[15]. Common side effects include sedation and dizziness, which may be additive with opioids.

Pregabalin has more predictable oral bioavailability and faster onset than gabapentin. Starting doses of 50-75 mg twice daily are titrated to 150-300 mg twice daily. Pregabalin may be preferred when rapid titration is needed or gabapentin absorption is unreliable ^[19].

Gabapentinoids should be initiated early when neuropathic pain or pruritus is anticipated, particularly in patients with deep partial-thickness or full-thickness burns involving nerve-rich areas.

Anxiolytics

Anxiety amplifies pain perception, and burn patients frequently report anxiety as a major contributor to their pain experience ^[4][13]. Benzodiazepines serve a specific role in procedural pain management:

Midazolam (0.5-2 mg IV) provides rapid anxiolysis and amnesia for short procedures. Its short duration of action makes it suitable for dressing changes. It is the standard co-agent with ketamine for procedural sedation ^[16][17].

Lorazepam (0.5-2 mg IV or oral) has a longer duration and is useful for scheduled anxiolysis in patients with persistent anxiety between procedures. It lacks active metabolites, making it preferable to diazepam in burn patients with hepatic stress.

Benzodiazepines are adjuncts to analgesia, not substitutes. They should not be used in place of adequate pain control, as sedation without analgesia masks rather than treats pain ^[20].

Regional Anesthesia

A "regional-first" approach engages anesthesiology and pain medicine in the burn center workflow ^[2]. Relevant techniques include:

• Infraclavicular/supraclavicular blocks for upper extremity coverage
• Erector spinae plane and quadratus lumborum blocks for the trunk
• Fascia iliaca and sciatic blocks for lower extremity donor and recipient sites

Regional anesthesia reduces opioid requirements while facilitating early therapy and mobility ^[2]. In pediatric burn reconstructive surgery, ultrasound-guided regional anesthesia with continuous catheters provided sustained comfort benefit through postoperative day 2 ^[10].

Regional Anesthesia for Enzymatic Debridement

Regional anesthesia was used in 96% of 112 bromelain-based enzymatic debridement cases, with pain control achieved in 61% during the first 48 hours and opioids required in only 12.5% ^[12]. A separate study of 32 patients found no significant increase in pain scores during enzymatic debridement across anesthetic modalities ^[11].

Nonpharmacologic Interventions

A systematic review of 15 randomized controlled trials found nonpharmacologic procedural pain management (virtual reality, distraction devices, child life therapy, music therapy, hypnosis) reduced mid-procedure pain by 19.7% and post-procedure pain by 20.1% compared to controls ^[5]. Virtual reality during adult burn dressing changes showed effective distraction, high satisfaction, and patient desire for future use, though some noted reduced nurse communication and headset-related discomfort ^[6].

Nonpharmacologic interventions are adjuncts to pharmacologic therapy, not replacements. They are most effective when integrated into a multimodal protocol that includes adequate background analgesia, procedural pre-medication, and anxiolysis ^[5][20].

Pediatric Considerations

Children pose unique challenges due to physiologic, psychologic, and anatomic differences compounded by burn-induced alterations in medication response and elimination ^[3][20]. Age-appropriate pain assessment tools are essential: the FLACC scale (Face, Legs, Activity, Cry, Consolability) for preverbal children, the Wong-Baker Faces scale for children aged 3-8, and numeric rating scales for older children.

Pharmacologic management follows the same multimodal principles as adults, but weight-based dosing, developmental pharmacokinetics, and the psychological impact of repeated painful procedures require careful attention ^[3][20]. Ketamine is particularly useful in pediatric procedural sedation because it maintains airway reflexes and spontaneous ventilation ^[20]. Nonpharmacologic techniques (child life therapy, directed play, virtual reality, cartoon distraction) have the strongest evidence base in the pediatric burn population ^[5].

Patient Education

Patients specifically requested more education on sleep and pain medications, alternative treatments, weaning and addiction risk, and recovery timelines. Written pamphlets were the most desired education format ^[4].

Discharge Opioid Stewardship

While 90% of patients received opioids at discharge, most discontinued by day 30. High morphine equivalent doses at discharge significantly increased long-term use risk (OR 6.06 at 60 days), as did pre-injury drug use (OR 7.67) ^[7]. These data support minimizing discharge opioid doses, establishing tapering plans before discharge, and scheduling early outpatient follow-up for pain reassessment.

Substance Use Disorders

Stimulant-positive patients (16.8% of admissions) had longer stays (17.7 vs 10.7 days) and higher complication rates, yet only 12.6% received addiction medicine consultation ^[8]. Systematic integration of addiction services into burn care is needed. Screening for substance use at admission and early involvement of addiction medicine for positive screens should be standard practice ^[8].

Chronic Neuropathic Pain

When pharmacologic management with gabapentinoids fails to control chronic neuropathic burn pain, surgical options include evaluation with diagnostic nerve blocks followed by nerve decompression, neuroma excision, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) ^[9]. Surgical management should be considered a second-line approach after pharmacologic therapy has been optimized.

Controversies and Evidence Gaps

Opioid dosing protocols for burn patients lack standardization despite the known pharmacokinetic alterations that affect drug behavior. Whether augmented renal clearance-based dosing adjustments improve outcomes has not been prospectively studied. Ketamine dosing protocols for procedural pain vary widely across centers, from sub-dissociative doses for analgesia to dissociative doses for dressing changes, without consensus guidelines ^[17][18]. Methadone has theoretical advantages for chronic burn pain (NMDA antagonism, long half-life) but lacks burn-specific dosing studies ^[21]. The role of IV acetaminophen as a standard component of the multimodal burn pain protocol has not been evaluated in a burn-specific randomized trial. Gabapentinoid dosing for burn neuropathic pain is extrapolated from other neuropathic pain populations; burn-specific titration protocols do not exist. Virtual reality shows promise as a nonpharmacologic adjunct ^[5][6], but optimal content, session duration, and integration with pharmacologic therapy remain undefined. The transition from acute to chronic pain management is poorly protocolized, and the risk of opioid dependence at discharge is real ^[7]. Regional anesthesia adoption in burn centers remains limited by anesthesiology workforce availability and the logistical challenges of placing blocks in patients with extensive wounds ^[2].

References

[1] Griggs C et al. "Sedation and Pain Management in Burn Patients." Clin Plast Surg 2017;44(3):535-540. PMID: 28576242. [2] Sheckter CC et al. "Techniques and strategies for regional anesthesia in acute burn care -- a narrative review." Burns Trauma 2021;9:tkab015. PMID: 34285927. [3] Fagin A, Palmieri TL. "Considerations for pediatric burn sedation and analgesia." Burns Trauma 2017;5:28. PMID: 29051890. [4] Duchin ER et al. "Burn patients' pain experiences and perceptions." Burns 2021;47(7):1627-1634. PMID: 33642121. [5] Gillum M et al. "Nonpharmacologic Management of Procedural Pain in Pediatric Burn Patients: A Systematic Review of Randomized Controlled Trials." J Burn Care Res 2022;43(2):368-373. PMID: 34534314. [6] Goruc R, Oztekin SD. "Virtual Reality During Burn Dressing: Are Patients Satisfied With Their Experiences?" PMID: 41188116. [7] Yenikomshian HA et al. "Outpatient opioid use of burn patients: A retrospective review." Burns 2019;45(8):1737-1742. PMID: 31229299. [8] Stanton EW et al. "Integrating Addiction Medicine Into Burn Care: Optimizing Pain Management in Stimulant-Positive Patients." J Burn Care Res 2025;46(4):725-729. PMID: 40814752. [9] Ku YC et al. "Surgical Management of Chronic Neuropathic Burn Pain." Clin Plast Surg 2024;51(3):419-434. PMID: 38789151. [10] 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. PMID: 25412051. [11] Buta MR et al. "Pain Management during Bromelain-Based Enzymatic Debridement (NexoBrid) in a USA Adult Burn Center." PMID: 39600009. [12] Acevedo ML et al. "Pain Management in Burned Patients Treated with Bromelain-Based Enzymatic Debridement." PMID: 40095533. [13] James DL, Jowza M. "Principles of Burn Pain Management." Clin Plast Surg 2017;44(4):737-747. PMID: 28888299. [14] Manasyan A et al. "Ibuprofen is Not Associated With an Elevated Bleeding Risk or Transfusion Requirement in Skin Grafting for Patients With Burn Injuries." J Burn Care Res 2025;46(3):642-645. PMID: 40036242. [15] Jaehde U, Sörgel F. "Clinical pharmacokinetics in patients with burns." Clin Pharmacokinet 1995;29(1):15-28. PMID: 7586895. [16] Gregoretti C et al. "Analgo-sedation of patients with burns outside the operating room." Drugs 2008;68(17):2427-43. PMID: 19016572. [17] Brennan PG et al. "Intravenous Ketamine as an Adjunct to Procedural Sedation During Burn Wound Care and Dressing Changes." J Burn Care Res 2019;40(2):246-250. PMID: 30189001. [18] Lintner AC et al. "Oral Administration of Injectable Ketamine During Burn Wound Dressing Changes." J Pharm Pract 2019;34(3):423-427. PMID: 31537149. [19] Chung BY et al. "Post-Burn Pruritus." Int J Mol Sci 2020;21(11):3880. PMID: 32485929. [20] Bayat A et al. "Analgesia and sedation for children undergoing burn wound care." Expert Rev Neurother 2010;10(11):1747-59. PMID: 20977331. [21] Kreutzwiser D, Tawfic QA. "Methadone for Pain Management: A Pharmacotherapeutic Review." CNS Drugs 2020;34(8):827-839. PMID: 32564328.