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Meta-Analysis
. 2024 Jun 5;6(6):CD013468.
doi: 10.1002/14651858.CD013468.pub2.

Interventions for postburn pruritus

Sarthak Sinha  1 , Vincent A Gabriel  2 , Rohit K Arora  1 , Wisoo Shin  1 , Janis Scott  3 , Shyla K Bharadia  2 , Myriam Verly  4 , Waleed M Rahmani  1 , Duncan A Nickerson  5 , Frankie Og Fraulin  4   6 , Pallab Chatterjee  7 , Rajeev B Ahuja  8 , Jeff A Biernaskie  1
Affiliations
Meta-Analysis

Interventions for postburn pruritus

Sarthak Sinha et al. Cochrane Database Syst Rev. .

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00731367 NCT00859547 NCT01214980 NCT00324311 NCT03777891.

PubMed Disclaimer

Conflict of interest statement

Sarthak Sinha: I have authored/co‐authored primary and opinion articles that relate to potential treatments for wound healing and tissue fibrosis.

Vincent Gabriel: works as a health professional and was involved in two studies that were eligible for inclusion in this review. Vincent did not make eligibility decisions, extract data from, or carry out risk of bias or GRADE assessment for either of these studies.

Duncan Nickerson: works as a health professional.

Frankie Fraulin: works as a health professional.

Wisoo Shin: none known.

Waleed Rahmani: works as a health professional.

Pallab Chatterjee: works as a health professional.

Rohit K Arora: none known.

Janis Scott: works as a health professional.

Shyla K Bharadia: none known.

Myriam Verly: works as a health professional.

Rajeev Ahuja: I have performed prospective randomised controlled trials assessing the efficacy of cetirizine, gabapentin (Ahuja 2011), and pregabalin (Ahuja 2013) for postburn pruritus. These trials were found to be eligible for inclusion in this review. Risk of bias assessment, decision to include or exclude, data extraction, and checking were all performed by members of the review team not associated with these trials.

Jeff Biernaskie: I have received consultancy fees (stock options) from Quthero Inc. and consultancy fees from Reveille Inc. I hold the Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration. Funds from this have been used to support trainee stipends during the course of this review.

Figures

1
1
PRISMA flow diagram
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Doxepin cream vs oral antihistamine, Outcome 1: Change in burn‐related pruritus
1.2
1.2. Analysis
Comparison 1: Doxepin cream vs oral antihistamine, Outcome 2: Adverse events
2.1
2.1. Analysis
Comparison 2: Doxepin cream vs placebo cream, Outcome 1: Change in burn‐related pruritus
2.2
2.2. Analysis
Comparison 2: Doxepin cream vs placebo cream, Outcome 2: Adverse events
3.1
3.1. Analysis
Comparison 3: Gabapentin vs cetirizine (antihistamine), Outcome 1: Change in burn‐related pruritus
3.2
3.2. Analysis
Comparison 3: Gabapentin vs cetirizine (antihistamine), Outcome 2: Adverse events (somnolence)
4.1
4.1. Analysis
Comparison 4: Pregabalin vs cetirizine plus pheniramine maleate (antihistamines), Outcome 1: Change in burn‐related pruritus
4.2
4.2. Analysis
Comparison 4: Pregabalin vs cetirizine plus pheniramine maleate (antihistamines), Outcome 2: Adverse events (somnolence)
5.1
5.1. Analysis
Comparison 5: Ondansetron vs diphenhydramine (antihistamine), Outcome 1: Change in burn‐related pruritus
6.1
6.1. Analysis
Comparison 6: CQ‐01 (hydrogel) vs control, Outcome 1: Change in burn‐related pruritus (visual analogue JW pruritic score)
7.1
7.1. Analysis
Comparison 7: Silicone gel vs placebo, Outcome 1: Change in burn‐related pruritus
7.2
7.2. Analysis
Comparison 7: Silicone gel vs placebo, Outcome 2: Pain
8.1
8.1. Analysis
Comparison 8: Enalapril ointment vs placebo, Outcome 1: Change in burn‐related pruritus
9.1
9.1. Analysis
Comparison 9: Provase moisturiser vs control moisturiser, Outcome 1: Change in burn‐related pruritus
9.2
9.2. Analysis
Comparison 9: Provase moisturiser vs control moisturiser, Outcome 2: Adverse events
11.1
11.1. Analysis
Comparison 11: Massage therapy vs standard care, Outcome 1: Change in burn‐related pruritus
11.2
11.2. Analysis
Comparison 11: Massage therapy vs standard care, Outcome 2: Pain
12.1
12.1. Analysis
Comparison 12: Therapeutic touch vs nursing presence, Outcome 1: Change in burn‐related pruritus
12.2
12.2. Analysis
Comparison 12: Therapeutic touch vs nursing presence, Outcome 2: Pain
13.1
13.1. Analysis
Comparison 13: Extracorporeal shock wave therapy vs sham, Outcome 1: Change in burn‐related pruritus
13.2
13.2. Analysis
Comparison 13: Extracorporeal shock wave therapy vs sham, Outcome 2: Pain
13.3
13.3. Analysis
Comparison 13: Extracorporeal shock wave therapy vs sham, Outcome 3: Participant health‐related quality of life
14.1
14.1. Analysis
Comparison 14: Enhanced education on silicone gel sheeting vs conventional education, Outcome 1: Change in burn‐related pruritus
14.2
14.2. Analysis
Comparison 14: Enhanced education on silicone gel sheeting vs conventional education, Outcome 2: Pain
15.1
15.1. Analysis
Comparison 15: Pulsed dye laser vs non‐treated controls, Outcome 1: Change in burn‐related pruritus
16.1
16.1. Analysis
Comparison 16: Fractional CO2 laser vs untreated control, Outcome 1: Change in burn‐related pruritus
16.2
16.2. Analysis
Comparison 16: Fractional CO2 laser vs untreated control, Outcome 2: Pain
17.1
17.1. Analysis
Comparison 17: Pulsed high‐intensity laser vs placebo laser, Outcome 1: Change in burn‐related pruritus
17.2
17.2. Analysis
Comparison 17: Pulsed high‐intensity laser vs placebo laser, Outcome 2: Pain
17.3
17.3. Analysis
Comparison 17: Pulsed high‐intensity laser vs placebo laser, Outcome 3: Participant health‐related quality of life
18.1
18.1. Analysis
Comparison 18: Transcutaneous electrical nerve stimulation vs standard care, Outcome 1: Change in burn‐related pruritus
19.1
19.1. Analysis
Comparison 19: Transcranial direct current stimulation vs sham stimulation, Outcome 1: Change in burn‐related pruritus
19.2
19.2. Analysis
Comparison 19: Transcranial direct current stimulation vs sham stimulation, Outcome 2: Pain
20.1
20.1. Analysis
Comparison 20: Cetirizine/cimetidine combination vs diphenhydramine/placebo combination, Outcome 1: Change in burn‐related pruritus
21.1
21.1. Analysis
Comparison 21: Lemon balm tea vs standard care, Outcome 1: Change in burn‐related pruritus (VAS)
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References

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Caruso 2009 {published data only}
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Chi 2015 {published data only}
    1. Chi YF, Chai JK, Luo HM, Zhang QX, Feng R. Safety of recombinant human granulocyte-macrophage colony-stimulating factor in healing pediatric severe burns. Genetics and Molecular Research 2015;14(1):2735-41. [DOI: 10.4238/2015.March.31.3] [PMID: ] - DOI - PubMed
Cho 2012 {published data only}
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Cuignet 2004 {published data only}
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Cuignet 2015 {published data only}
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Demling 2001 {published data only}
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De Oliveira 2018 {published data only}
    1. De Oliveira RA, Boson LL, Portela SM, Maia Filho AL, De Oliveira Santiago D. Low-intensity LED therapy (658 nm) on burn healing: a series of cases. Lasers in Medical Science 2018;33(4):729-35. [PMID: ] - PubMed
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    1. Gardien KL, Olde Damink LH, Heschel I, Vloemans AF, Tempelman FR, Van Zuijlen PP, et al, Euroskingraft Study Group. A novel dermal substitute in combination with a split-thickness skin autograft for burn wound treatment: preliminary results of a safety trial. Wound Repair and Regeneration 2014;22(5):A80. [DOI: 10.1111/wrr.12242] [PMID: ] - DOI - PubMed
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Goutos 2010 {published data only}
    1. Goutos I, Eldardiri M, Khan AA, Dziewulski P, Richardson PM. Comparative evaluation of antipruritic protocols in acute burns. The emerging value of gabapentin in the treatment of burns pruritus. Journal of Burn Care & Research 2010;31(1):57-63. [PMID: ] - PubMed
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Greenhalgh 1994 {published data only}
    1. Greenhalgh DG, Rieman M. Effects of basic fibroblast growth factor on the healing of partial‐thickness donor sites: a prospective, randomized, double‐blind trial. Wound Repair and Regeneration 1994;2(2):113-21. [DOI: 10.1046/j.1524-475X.1994.20205.x] [PMID: ] - DOI - PubMed
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Hernández 2011 {published data only}
    1. Hernández R, Garibay M. Silver sulfadiazine cream versus topical application in second degree burns [Sulfadiazina de plata en crema versus suspensión tópica en quemaduras de segundo grado]. Revista Mexicana de Pediatría 2011;78(2):56-9.
Heydarikhayat 2018 {published data only}
    1. Heydarikhayat N, Ashktorab T, Rohani C, Zayeri F. Effect of post-hospital discharge follow-up on health status in patients with burn injuries: a randomized clinical trial. International Journal of Community Based Nursing and Midwifery 2018;6(4):293. [PMC6226610] [PMID: ] - PMC - PubMed
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Hultman 2014 {published data only}
    1. Hultman CS, Friedstat JS, Edkins RE, Cairns BA, Meyer AA. Laser resurfacing and remodeling of hypertrophic burn scars: the results of a large, prospective, before-after cohort study, with long-term follow-up. Annals of Surgery 2014;260(3):519-29. [DOI: 10.1097/SLA.0000000000000893] [PMID: ] - DOI - PubMed
Ioannovich 2003 {published data only}
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Issler‐Fisher 2020 {published data only}
    1. Issler‐Fisher AC, Fisher OM, Haertsch P, Li Z, Maitz PK. Ablative fractional resurfacing with laser‐facilitated steroid delivery for burn scar management: does the depth of laser penetration matter? Lasers in Surgery and Medicine 2020;52(2):149-58. [DOI: 10.1002/lsm.23166] [PMID: ] - DOI - PubMed
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    1. Johansen AM, Sorensen B. After-treatment of burns-grafted and spontaneously healed--in particular a trial of aliderm leo ointment. Scandinavian Journal of Plastic and Reconstructive Surgery 1970;4(1):41-4. [DOI: 10.3109/02844317009038442] [PMID: ] - DOI - PubMed
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    1. Joo SY, Cho YS, Cho SR, Kym D, Seo CH. Effects of pain Scrambler therapy for management of burn scar pruritus: a pilot study. Burns 2017;43(3):514-9. [DOI: 10.1016/j.burns.2016.09.028] [PMID: ] - DOI - PubMed
Joo 2018b {published data only}
    1. Joo SY, Kim JB, Cho YS, Cho YS, Seo CH. Effect of cold pack therapy for management of burn scar pruritus: a pilot study. Burns 2018;44(4):1005-10. [PMID: ] - PubMed
Jung 2009 {published data only}
    1. Jung SI, Seo CH, Jang K, Ham BJ, Choi IG, Kim JH, et al. Efficacy of naltrexone in the treatment of chronic refractory itching in burn patients: preliminary report of an open trial. Journal of Burn Care & Research 2009;30(2):257-60. [DOI: 10.1097/BCR.0b013e318198a282] [PMID: ] - DOI - PubMed
Kemp‐Offenberg 2015 {published data only}
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    1. Ki SH, Ma SH, Choi JH, Sim SH, Kim HM. Treating skin graft donor sites: a comparative study between remnant skin use and polyurethane foam. Journal of Wound Care 2019;28(7):469-77. [DOI: 10.12968/jowc.2019.28.7.469] [PMID: ] - DOI - PubMed
Kisch 2021 {published data only}
    1. Kisch T, Stang FH, Mailaender P, Schleusser S, Michel D, Trieb R, et al. Smart Scar Care - Industry 4.0 in individualized compression garments: a randomized controlled crossover feasibility study. Plastic and Reconstructive Surgery Global Open 2021;9(7):1-10. - PMC - PubMed
Kono 2005 {published data only}
    1. Kono T, Erçöçen AR, Nakazawa H, Nozaki M. Treatment of hypertrophic scars using a long-pulsed dye laser with cryogen-spray cooling. Annals of Plastic Surgery 2005;54(5):487-93. [DOI: 10.1097/01.sap.0000155276.93061.93] [PMID: ] - DOI - PubMed
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Lee 2021 {published data only}
    1. Lee JH, Seo CE, Song WJ, Kwon MJ, Park YS, Ko JH, et al. Combination treatment utilizing fractional ablative and continuous wave CO2 lasers for hypertrophic burn scars. Burns 2021;47(5):1084-93. [DOI: 10.1016/j.burns.2020.10.015] [PMID: ] - DOI - PubMed
Li 2015 {published data only}
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Li 2018 {published data only}
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Li‐Tsang 2006 {published data only}
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Lv 2019 {published data only}
    1. Lv K, Liu H, Xiao S, Xia Z. 318 Efficacy of whole scar ablative fractional carbon dioxide laser treatment in patients with large area of burn scar: a prospective cohort study. Journal of Burn Care & Research 2019;40:S136-7. [DOI: 10.1093/jbcr/irz013.231] - DOI
Lv 2021 {published data only}
    1. Lv K, Liu H, Xu H, Wang C, Zhu S, Lou X, et al. Ablative fractional CO2 laser surgery improving sleep quality, pain and pruritus in adult hypertrophic scar patients: a prospective cohort study. Burns & Trauma 2021;9:1-11. [PMID: ] - PMC - PubMed
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Matheson 2001 {published data only}
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    1. Memon AR, Tahir SM, Khushk IA, Memon GA. Therapeutic effects of honey versus silver sulphadiazine in the management of burn injuries. Journal of Liaquat University of Medical & Health Sciences 2005;4:100-4.
Mileski 2003 {published data only}
    1. Mileski WJ, Burkhart D, Hunt JL, Kagan RJ, Saffle JR, Herndon DN, et al. Clinical effects of inhibiting leukocyte adhesion with monoclonal antibody to intercellular adhesion molecule-1 (enlimomab) in the treatment of partial-thickness burn injury. Journal of Trauma and Acute Care Surgery 2003;54(5):950-8. [DOI: 10.1097/01.TA.0000030626.84680.11] [PMID: ] - DOI - PubMed
Miletta 2019 {published data only}
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Mohammadi 2017 {published data only}
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Moortgat 2015 {published data only}
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Mumtaz 2008 {published data only}
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Namviriyachote 2012 {published data only}
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Nasiri 2016 {published data only}
    1. Nasiri E, Hosseinimehr SJ, Hosseinzadeh AZ, Azadbakht M, Akbari J, Azadbakht M. The effects of Arnebia euchroma ointment on second-degree burn wounds: a randomized clinical trial. Journal of Ethnopharmacology 2016;189:107-16. [DOI: 10.1016/j.jep.2016.05.029] [PMID: ] - DOI - PubMed
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Nedelec 2020 {published data only}
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Parlak 2010 {published data only}
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Patiño 1999 {published data only}
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Sheridan 1997 {published data only}
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Tawfic 2019 {published data only}
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Wang 2017 {published data only}
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References to ongoing studies

IRCT20170609034406N7 {published data only}
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IRCT20180609040016N2 {published data only}
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IRCT20210306050596N1 {published data only}
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ISRCTN10393098 {published data only}ISRCTN10393098
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References to other published versions of this review

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