James Hwang

Catechol-O-Methyltransferase Genotype Predicts Pain Severity in Hospitalized Burn Patients

Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-methyltransferase (COMT), may predict pain severity after thermal burn injury. The authors evaluated the association between COMT genotype and pain intensity in 57 individuals hospitalized after thermal burn injury. Consenting participants at four burn centers were genotyped and completed daily 0 to 10 numeric rating scale pain assessments on 2 consecutive days including evaluation of waking, least, and worst pain. The association between COMT genotype and individual pain outcomes was calculated using a linear mixed model adjusting for sociodemographic and burn injury characteristics. Overall pain (combination of least, worst, and waking pain scores) was significantly higher in patients with a COMT pain vulnerable genotype (6.3 [0.4] vs 5.4 [0.4], P = .037). Individuals with a COMT pain vulnerable genotype also had significantly higher “least pain” scores (3.8 [0.5] vs 2.6 [0.4], P = .017) and significantly higher pain on awakening (6.8 [0.5] vs 5.3 [0.4], P = .004). Differences in worst pain according to genotype group were not significant. COMT pain vulnerable genotype was a stronger predictor of overall pain severity than burn size, burn depth, or time from admission to pain interview assessment. These findings suggest that genetic factors influencing stress system function may have an important influence on pain severity after burn injury. Further studies of genetic predictors of pain after burn injury are needed.

Results of a pilot multicenter genotype-based randomized placebo-controlled trial of propranolol to reduce pain after major thermal burn injury.

Background:Results of previous studies suggest that &bgr;-adrenoreceptor activation may augment pain, and that &bgr;-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high-activity haplotype. Materials and Methods:Consenting patients admitted for thermal burn injury at participating burn centers were genotyped; those who were not high-activity COMT homozygotes were randomized to propranolol 240 mg/d or placebo. Primary outcomes were study feasibility (consent rate, protocol completion rate) and pain scores on study days 5 to 19. Secondary outcomes assessed pain and posttraumatic stress disorder symptoms 6 weeks postinjury. Results:Seventy-seven percent (61/79) of eligible patients were consented and genotyped, and 77% (47/61) were genotype eligible and randomized. Ninety-one percent (43/47) tolerated study drug and completed primary outcome assessments. In intention-to-treat and per-protocol analyses, patients randomized to propranolol had worse pain scores on study days 5 to 19. Conclusions:Genotype-specific pain medication interventions are feasible in hospitalized burn patients. Propranolol is unlikely to be a useful analgesic during the first few weeks after burn injury.

Chest high-frequency oscillatory treatment for severe atelectasis in a patient with toxic epidermal necrolysis.

Atelectasis is a significant risk factor for the development of pneumonia, especially in pediatric populations more prone to alveolar collapse or those who may have weakened muscular tone. The Metaneb system is a pneumatic, noninvasive physiotherapy technique that delivers chest high-frequency oscillations. Chest high-frequency oscillations have been shown to enhance mucociliary clearance of secretions and help resolve patchy atelectasis. This report describes the case of a 17-year-old female patient who developed significant left-sided atelectasis after extubation and was effectively managed with complete resolution of her atelectasis with the Metaneb system, obviating the need for reintubation.

Chronic Pain and Itch are Common, Morbid Sequelae Among Individuals Who Receive Tissue Autograft After Major Thermal Burn Injury

Objective: Pain and itch symptoms are common after major thermal burn injury (MThBI)—requiring tissue autografting. To our knowledge, no prospective longitudinal studies have characterized pain and itch outcomes after tissue autografting and associations between and functional interference caused by such symptoms. Materials and Methods: We prospectively evaluated burn graft site and tissue donor site pain and itch severity (0 to 10, numeric rating scale) over 1 year among a representative cohort of MThBI survivors (n=96) who received tissue autografting within 14 days of MThBI. Results: Nearly all participants had moderate or severe burn pain at the time of enrollment. Most individuals experienced an upper extremity burn with donor tissue taken from thigh. Persistent moderate or severe burn graft site pain declined thereafter, but remained common, with 25/90 (28%), 24/77 (31%), and 17/82 (21%) experiencing moderate or severe pain at 6 weeks, 3 months, and 6 months, respectively. Although there was improved function after immediate postinjury decline in all participants, those who had moderate or severe pain showed worse functional outcomes at each timepoint. Significant correlations were present between itch and pain burden over time at the same site (ie, autograft site r=0.629, P<0.01) and also across sites (ie, autograft and donor site itch r=0.552, P<0.01). Discussion: Pain and itch are common after MThBI, are temporally and spatially concordant and cause significant impact on daily function. Further studies are needed to better understand pain and itch symptom pathogenesis after MThBI, to reduce the tremendous suffering and decline.

Hypertrophic Scar Severity at Autograft Sites Is Associated with Increased Pain and Itch after Major Thermal Burn Injury

Approximately three quarters of major thermal burn injury (MThBI) survivors suffer from hypertrophic scarring (HTS) and over half experience chronic pain or itch. In survivors of MThBI, HTS and chronic pain or itch are considered one of the greatest unmet challenges of postburn injury care and psychosocial reintegration. Although scarring, itch, and pain have been clinically associated, there are no prospective, multisite studies examining tissue autograft site pain or itch and scar outcomes. The authors collected a representative cohort (n = 56) of MThBI survivors who received autografting within 14 days of injury and evaluated graft-site pain or itch severity (0-10 Numeric Rating Scale) and HTS using a validated scar photograph assessment scale 6 months following MThBI. Given that stress is known to influence wound healing, the authors also assessed the relationship between previous trauma exposure, peritraumatic stress, preburn overall health (SF-12), scarring, and chronic pain or itch severity using Spearmans correlation. Association between HTS and chronic pain or itch was significant in a linear regression model adjusted for age, sex, and ethnicity (β = 0.2, P = .033 for pain, β = 0.2, P = .019 for itch). Results indicate that prior trauma exposure is inversely correlated (r = -.363, P = .030) with scar severity, but not pain or itch severity 6 months after MThBI. Study results suggest that preburn chronic pain or itch is associated with pathological scarring 6 months following MThBI. Results also indicate that stress may improve scarring after MThBI. Further work to understand the mechanisms that underlie both HTS and chronic pain or itch and their relationship to chronic stress is critical to the development of novel therapies to assist burn survivors recover.

Pain and itch outcome trajectories differ among European American and African American survivors of major thermal burn injury.

Abstract More than half of individuals experiencing major thermal burn injury (MThBI) receive an autologous skin graft (autograft), in which skin is removed from a healthy “donor” site and transplanted to the burn site. Persistent pain and itch at the graft site are major causes of suffering and disability in MThBI survivors. African Americans have a higher risk of MThBI, and in other clinical settings African Americans experience a greater burden of pain and itch relative to European Americans. However, to our knowledge, ethnic differences in skin graft site pain and itch outcomes after MThBI have not been assessed. We evaluated skin graft site pain and itch severity (0-10 Numeric Rating Scale [NRS]) over 1 year in a prospective multicenter cohort sample of African Americans and European Americans. In adjusted linear mixed models, African Americans experienced a slower rate of pain resolution in the acute phase of recovery (&bgr; = −0.05 vs −0.08 NRS points per day, P < 0.001), which resulted in a higher pain severity in the persistent phase of recovery (NRS mean difference = 1.21, 95% confidence interval [0.12-2.29]), although not statistically significant after correction for multiple comparisons. African Americans also experience greater itch severity in 6 weeks to 12 months after burn injury compared with European Americans (NRS mean difference = 1.86 [0.80-2.93]), which results from a faster rate of itch development in African Americans in the acute recovery phase after burn injury. Future studies may improve outcomes in African Americans and lead to new pathogenic insights that benefit all burn injury survivors.