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Open Access

Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis

Christopher McGovern, Tara Quasim, Kathryn Puxty, Martin Shaw, Wijnand Ng, Charlotte Gilhooly, Nikolaos Arkoulis, Michael Basler, Alan Macfarlane, Lia Paton
DOI: 10.1136/tsaco-2021-000810 Published 25 October 2021
Christopher McGovern
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
2Anaesthesia & Critical Care, Glasgow Royal Infirmary, Glasgow, UK
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  • ORCID record for Christopher McGovern
Tara Quasim
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
2Anaesthesia & Critical Care, Glasgow Royal Infirmary, Glasgow, UK
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Kathryn Puxty
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
2Anaesthesia & Critical Care, Glasgow Royal Infirmary, Glasgow, UK
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Martin Shaw
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
3Department of Clinical Physics and Bioengineering, NHS Greater Glasgow and Clyde, Glasgow, UK
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Wijnand Ng
4Medical Student, University of Glasgow, Glasgow, UK
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Charlotte Gilhooly
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
2Anaesthesia & Critical Care, Glasgow Royal Infirmary, Glasgow, UK
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Nikolaos Arkoulis
5Plastic and Burn Surgery, Glasgow Royal Infirmary, Glasgow, UK
6Honorary Clinical Senior Lecturer (Medicine), University of Glasgow, Glasgow, UK
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Michael Basler
7Anaesthesia and Pain Medicine, Glasgow Royal Infirmary, Glasgow, UK
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Alan Macfarlane
1Anaesthesia, Critical Care and Peri-operative Medicine, University of Glasgow, Glasgow, UK
7Anaesthesia and Pain Medicine, Glasgow Royal Infirmary, Glasgow, UK
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Lia Paton
2Anaesthesia & Critical Care, Glasgow Royal Infirmary, Glasgow, UK
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  • Figure 1
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    Figure 1

    Forest plot showing the reduction in mean VAS (Visual Analog Scale) in each treatment arm, comparing gabapentinoids with controls. 95% CI, 95% confidence interval.

  • Figure 2
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    Figure 2

    Forest plot showing the reduction in mean VAS (Visual Analog Scale) in each treatment arm, comparing topical doxepin with controls. 95% CI, 95% confidence interval.

Tables

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  • Table 1

    Randomized controlled trials of gabapentinoids

    StudyYearSetting/designInclusion criteriaPatient numberAge (years)Intervention groupsGabapentinoid dosing regimenOutcomesFollow-up
    Zheng et al302015Single center RCT>5% TBSA, second degree burn, >80% healed or healed within 3 months5818 to 60
    1. Gabapentin

    2. Cetirizine

    3. Placebo

    Gabapentin 300 mg twice dailyPruritus VAS28 days
    Ahuja et al222013Single center RCT>5% TBSA, 80% epithelialized or healed within 1 month8018 to 60Four groups:
    1. Antihistamine

    2. Pregabalin and antihistamine

    3. Placebo

    4. Pregabalin

    Pregabalin varied with severity of pruritus:
    Mild—75 mg twice daily
    Moderate—75 mg three times a day
    Severe—150 mg twice daily
    Pruritus VAS28 days
    Ahuja et al212011Single center RCT>5% TBSA, 80% epithelialized or healed within 1 month6012 to 70Three groups:
    1. Cetirizine

    2. Gabapentin

    3. Combination cetirizine and gabapentin

    Gabapentin varied with severity of pruritus:
    Mild—300 mg once daily
    Moderate— 300 mg twice daily
    Severe—300 mg three times a day
    Pruritus VAS28 days
    Gray et al242011Single center RCTAdmitted to burn unit, >5% TBSA9018 to 65
    1. Pregabalin

    2. Placebo

    Pregabalin 75 mg twice daily, titrated up to 150 mg twice daily or 300 mg twice daily based on clinical responseNPS (includes itch score 0 to 10)
    Procedural pain score 0 to 10
    4-point side effect scale
    28 days
    • NPS, Neuropathic Pain Scale; QOL, quality of life; RCT, randomized controlled trial; TBSA, total body surface area.

  • Table 2

    Observational studies of gabapentinoids

    StudyYearSetting/designInclusion criteriaPatient numberAge (years)Intervention groupsDosing regimenOutcomesFollow-up
    Kneib et al262019Single center retrospective cohort studyAdmitted to burn unit, complained of itch411>14Use of neuropathic pain protocol.
    Analyzed by group:
    1. Gabapentin at <72 hours

    2. Gabapentin >72 hours

    3. No gabapentin

    Gabapentin 300 mg once daily increased every 2 days if NRS≥5 to max 900 mg three times a dayMorphine equivalent dose
    Total gabapentin use
    Pain and itch NRS
    Short Form-12 survey
    24 months
    Nieuwendijk et al282018Single center prospective observational studyIn burn ward or outpatient clinic, complained of itch413<13Not protocolized. Mixture of no treatment, gabapentin, and antihistamineGabapentin 5 mg/kgItch Man Scale 0 to 4
    Itch NRS (0 to 10)
    1 week to 3 months
    Kaul et al252018Single center retrospective observational studyPruritus or neuropathic pain on gabapentinoid1360 to 20Gabapentin only or in combination with pregabalinVarious gabapentin doses used from 50 mg three times a day to 1200 mg three times a day. Pregabalin 50 mg to 100 mg three times a day added if inadequate response to gabapentin.Retrospective review to describe effective dose of drugsUnclear
    Zachariah et al112012Single center prospective observational studyBurn 6 weeks to 2 years old, pruritus with failure of cetirizine and emollients234 to 60Gabapentin added if cetirizine inadequateAdults—gabapentin 100 mg twice daily, increased to max 300 mg three times a day
    Children—5 mg/kg twice daily to max 5 mg/kg three times a day
    Itch severity scale (7 to 21 points)6 months
    Goutos et al142010Single center prospective observational studyWithin 72 hours of injury, admitted to burn unit, sense of itch and urge to scratch91Adults and childrenTwo consecutive protocols. Gabapentin introduced early or late, compared with pre-protocol data.Adult 300 mg once daily titrated to 300 mg three times a day over 3 days
    Children 5 mg/kg once daily titrated to 5 mg/kg three times a day over 3 days
    Itch Man Scale 0 to 4Unclear. Only inpatient data.
    Mendham et al272004Single center prospective observational studyItching burn wound, admitted to burns unit35ChildrenGabapentin (no comparator or control)5 mg/kg three times a day to max 5 mg/kg twice daily plus 10 mg/kg nocteStaff or parent reporting of itch reductionUnclear. Some followed up for 18 months.
    • NRS, Numeric Rating Scale.

  • Table 3

    Studies of topical doxepin

    StudyYearSetting/designInclusion criteriaPatient numberInterventionControlOutcomesFollow-up
    Kwa et al332020Multicenter cross-over RCTHealed burn, itch VAS≥3, pruritic area <10%27Doxepin creamPlacebo creamPruritus VAS
    BIQ at week 2 and week 5
    5 weeks
    Kwa et al322019Multicenter RCTHealed burn, itch VAS≥331Doxepin cream and placebo tabletPlacebo cream and antihistamine tabletPruritus VAS
    BIQ
    QOL SF-36
    Somnolence
    Erythema
    12 weeks
    Demling et al342003Single center RCTHealed, <35% TBSA partial thickness burn, pruritic area <20%31DoxepinStandard carePruritus VAS
    Erythema (Vancouver Scar Scale)
    12 weeks
    Demling et al312002Single center RCTHealed burn, pruritic area <15%41DoxepinStandard carePruritus VAS
    Erythema (Vancouver Scar Scale)
    12 weeks
    • BIQ, Burn Itch Questionnaire; QOL SF-36, Quality of Life Short Form-36 questionnaire; VAS, Visual Analog Scale.

Supplementary Materials

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    [tsaco-2021-000810supp001.pdf]

Additional Files

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    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    • Data supplement 1
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Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis
Christopher McGovern, Tara Quasim, Kathryn Puxty, Martin Shaw, Wijnand Ng, Charlotte Gilhooly, Nikolaos Arkoulis, Michael Basler, Alan Macfarlane, Lia Paton
Trauma Surg Acute Care Open Oct 2021, 6 (1) e000810; DOI: 10.1136/tsaco-2021-000810

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Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis
Christopher McGovern, Tara Quasim, Kathryn Puxty, Martin Shaw, Wijnand Ng, Charlotte Gilhooly, Nikolaos Arkoulis, Michael Basler, Alan Macfarlane, Lia Paton
Trauma Surg Acute Care Open Oct 2021, 6 (1) e000810; DOI: 10.1136/tsaco-2021-000810
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Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis
Christopher McGovern, Tara Quasim, Kathryn Puxty, Martin Shaw, Wijnand Ng, Charlotte Gilhooly, Nikolaos Arkoulis, Michael Basler, Alan Macfarlane, Lia Paton
Trauma Surgery & Acute Care Open Oct 2021, 6 (1) e000810; DOI: 10.1136/tsaco-2021-000810
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