Interventions for postburn pruritus.

BACKGROUND: Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are. OBJECTIVES: To assess the effects of interventions for treating postburn pruritus in any care setting. SEARCH METHODS: In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies. AUTHORS' CONCLUSIONS: There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.

Adult Human Dermal Progenitor Cell Transplantation Modulates the Functional Outcome of Split-Thickness Skin Xenografts.

Following full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound "closure" in patients is autologous split-thickness skin grafting (STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.

Epidemiological analysis of pediatric burns in the Dominican Republic reveals a demographic profile at significant risk for electrical burns.

OBJECTIVE: Pediatric burns are preventable with legislative and infrastructural changes. Although retrospective audits of many low- and middle-income countries have aided preventative efforts, the epidemiological status of burns in the Caribbean is not known. This study characterizes pediatric burns in the Dominican Republic (DR) and compares these to age-matched North American records captured by the National Burn Repository. METHODS: A retrospective audit of 1600 patients admitted to the Unidad de Niños Quemados Dra. Thelma Rosario Hospital, the island's only major pediatric burn center, between January 2010 to March 2017 was performed. Epidemiological variables analyzed included age, gender, burn mechanism, year, month, city, admission duration, nationality, mortality, and %TBSA. RESULTS: Pediatric burn patients in the DR sustained larger burns (8.2% vs. 6.5% TBSA) and spent more days in the hospital (10 vs. 6 days). Females were overrepresented (M:F=1:1.5) and mortality amongst admitted patients was 4-fold higher (2.8% vs. 0.7%). Electrical burns were significantly overrepresented in DR (21%) compared to age-matched North American patients (2%). Although electrical burns were smaller (4% TBSA), compared to scald (14% TBSA), and flame (19% TBSA), these burns preferred hands and had a high mortality rate (3%). No significant seasonality in burn mechanisms were observed. Finally, we report geographical and age group differences in the distribution of burn mechanisms and highlight particularly vulnerable subpopulations. CONCLUSION: This investigation identifies a demographical profile where electrical burns account for a significant percentage of the burn population. This provides a basis for concentrating preventative efforts in vulnerable populations.

Burns from illegal cannabis oil manufacturing: a case series.

BACKGROUND: The increasing consideration of cannabis legalization in Canada and the United States has motivated physicians to assess its prospective impact on the health care system. Health care providers in the burns community are concerned about injuries sustained as a result of the illegal manufacturing of cannabis oil because it involves highly flammable reagents. METHODS: We report a retrospective case series of patients with cannabis oil burns (identified by evidence of combustion during cannabis oil manufacturing) treated from April 2012 to March 2014 at the Foothills Medical Centre in Calgary, Alberta, Canada. We compare the characteristics of these patients with those of patients admitted over the same period with any burns. RESULTS: We found that 12 (out of 161 patients) admitted over the review period sustained burns from cannabis oil manufacturing. Compared with patients in the total burn group, patients with cannabis oil burns were younger (75% and 48% were younger than 41 years in the group with cannabis oil burns and the total burn group, respectively), were more likely to be male (83% in the group with cannabis oil burns v. 74% in the total burn group) and sustained burns over a larger percentage of their total body surface area (24% v. 9%). Patients with cannabis oil burns also required extensive surgical management (skin grafting in 75% of cases) and spent a substantial amount of time (mean 32 d) in the burn unit. INTERPRETATION: Burns from illegal cannabis oil manufacturing are large, require extensive management and involve younger patients than burns in general. Given that the frequency of cannabis oil burns may increase in Canada after legalization, Canadian burn centres are encouraged to monitor and report on cases with this injury mechanism.

Burn clinical trials: A systematic review of registration and publications.

BACKGROUND: Randomized controlled clinical trials (CTs) are gold standard tools for assessing interventions. Although burn CTs have improved care, their status, publication frequency, and publication quality are not known. OBJECTIVES: (1) Characterize burn CTs by analyzing location, completion status, temporal trend, and funding sources. (2) Assess quality of trial reporting. DATA SOURCES: CT records were obtained from ClinicalTrials.gov and WHO's CT Registry (searched May 2017). Publications were obtained from PubMed, Google Scholar, OVID MEDLINE, and ClinicalTrials.gov (searched June 2017). PUBLICATION APPRAISAL: 23-item rubric adapted from CONSORT and ICH E3 guidelines. RESULTS: 738 burn CTs were identified globally, of which majority were publically-funded (77%), ongoing (52%), and assessed behavioral, pharmacological, device-based, dietary-based, and biological/procedural interventions. Amongst the ended trials, 69 (28%) published their findings. Significantly fewer industry-funded trials published findings (14% vs 33% publically-funded). Quality of reporting was suboptimal, and most underreported categories were trial phase, severity, and sample size estimation. LIMITATIONS: Incomplete, outdated, and non-registered CTs which are difficult to track. CONCLUSIONS: Burn trials are proliferating in number, location, and interventions assessed. Only a small proportion are published and quality of reporting is suboptimal. IMPLICATIONS OF KEY FINDINGS: Burn researchers should aim to register and report on all clinical trials regardless of outcome. Superior a priori design can reduce precocious termination and mandatory reporting of data fields can improve quality of reporting. Systematic review registration number: CRD42017068549.

Treating pain on skin graft donor sites: Review and clinical recommendations.

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

Response of human skin to esthetic scarification.

This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development.