A comparative analysis of cetirizine, gabapentin and their combination in the relief of post-burn pruritus☆
Introduction
Itch is a skin sensation leading to a desire to scratch [1]. Even though the incidence of post-burn pruritus is not known it inflicts an overwhelming number of patients who are hospitalized for burn management or where the burn wound takes more than three weeks to heal [2], [3], [4], [5]. Published studies report the incidence of post-burn itching between 80 and 100% [2], [3], [4], [5]. Itching can start a few days after burn injury and does not necessarily stop when wound healing is complete, continuing for up to 2 years in some patients [6]. The presence of an itch specific neuronal pathway has been established with a specific class of dorsal horn neurons projecting to the thalamus, which is distinct from the pain pathway [7], [8]. Yet, there is a complex interaction between pain and itch pathways [7], [8]. The inhibition of itch by pain is well known (the antipruritic effect of scratching) and conversely, inhibition of pain processing (by opioids) generates itch [7], [8]. Thus, the itch sensation is based on both increased activity in the itch pathway and a low level of activity in the pain pathway [8].
Histamines are released during the inflammatory process and as a byproduct of collagen production [9]; and increased amounts are also seen in granulation tissue [10]. As wound healing may be protracted in deep burns, requiring extensive collagen replacement, histamines are released for longer periods of time, which leads to persistent itch [9]. Infection can also prolong wound healing, and hypertrophic scarring also increases the levels of histamine released [9]. Other pharmacological mediators of itching in inflamed skin have been proposed viz. PGE2, tachykinins (calcitonin gene related peptide (CGRP) and substance P), opioid peptides, 5 hydroxytryptamine (5HT), interleukin-2 etc. [1]. Specific inhibitors of these mediators have been shown to alleviate itch, representing the targets for newer antipruritic therapy. The most commonly recommended therapy for post-burn itch has been with antihistaminics [4]. It is generally accepted that treatment with diphenhydramine, chlorpheniramine or hydroxyzine does not relieve post-burn itch effectively in a large number of patients and the medication also leads to sedation [2], [11].
With our current understanding of pathophysiology of post-burn itch a variety of agents like gabapentin [12], ondansetron [13] and naltrexone [14] have been used recently to relieve this distressing symptom. Of these agents, gabapentin is emerging as a ‘break through’ drug with favorable reports on its efficacy in relieving all kinds of pruritus [12], [15], [16], [17], [18]. Although, the interest in using gabapentin is increasing, the reports on its use in relieving post-burn pruritus are sparse, and there is no direct comparative evaluation of gabapentin and antihistaminics in such patients. Although, a recent study by Goutos et al. [18] compares two antipruritic protocols involving a combination of moisturizers, antihistaminics and gabapentin in a ‘ladder’ pattern, our current study not only compares the two drugs directly in management of acute pruritis [5], but also studies if their combination could be more effective, since the mechanisms of actions of the two drugs are completely different; gabapentin acting centrally and antihistaminics acting peripherally.
Section snippets
Materials and methods
The study was conducted from July’09 to October’09 in the Department of Burns, Plastic, Maxillofacial and Microvascular Surgery at Lok Nayak Hospital and associated Maulana Azad Medical College, New Delhi. Prior approval for the study was taken from the Ethics Committee of Lok Nayak Hospital.
Sixty adult patients in the post-burn healing phase (wounds healed less than one month back – in early remodeling phase) with complaints of itching were allocated, equally (20 each), to either of the three
Results
There was no significant difference in all the three groups with respect to mean age, sex distribution, mean percentage of TBSA burn and mean VAS score on day 0 (Table 4).The base values on day 0 being; mean age: Group A – 26.75 years, Group B – 28.65 years, Group C – 29.1 years; sex distribution (male to female): Group A – 12:8, Group B – 10:10, Group C – 9:11; mean percentage of total body surface area burn—Group A: 28%, Group B: 26%, Group C: 29%; and mean VAS score on day 0—Group A: 6.6,
Discussion
Burn patients in our hospital are treated primarily on conservative lines due to excessive burn load [20]. Because of a high mean TBSA burns and protracted healing, itch is a major problem amongst our burn patients in their rehabilitative stage. Vitale et al. [2] documented these factors to be the main reasons for severe post-burn itch. Standard therapies of itch management have included antihistaminics and emollients [11]. Cetirizine, a metabolite of hydroxyzine, is a selective antihistaminic
Conflict of interest
None of the authors has any conflict of interest with the drugs tested, or their manufacturers and distributors.
References (25)
- et al.
Pathophysiology of itching
Lancet
(1996) Burns pruritus—a study of current practices in the UK
Burns
(2010)- et al.
Itch
Lancet
(2003) - et al.
Scratching the surface—managing the itch associated with burns: a review of current knowledge
Burns
(2008) Gabapentin for the treatment of itching produced by burns and wound healing in children: a pilot study
Burns
(2004)- et al.
Naltrexone for the management of post burnpruritus: a preliminary report
Burns
(2008) - et al.
Gabapentin treatment for brachioradial pruritus
J Eur Acad Dermatol Venerol
(1999) - et al.
Cross-cultural adaptation and validation of the questionnaire for pruritus assessment for use in the French Canadian burn survivor population
Burns
(2008) - et al.
An analysis of 11196 burn admissions and evaluation of conservative management techniques
Burns
(2002) - et al.
Severe itching in the patient with burns
J Burn Care Rehabil
(1991)
Management of post burnitching and dryness
J Burn Care Rehabil
Itching following burns: epidemiology and predictors
Br J Dermatol
Cited by (53)
Pain Management in Burn Patients: Pharmacologic Management of Acute and Chronic Pain
2024, Clinics in Plastic SurgeryBurn Injury Complications Impacting Rehabilitation
2023, Physical Medicine and Rehabilitation Clinics of North AmericaPrescribing of Gabapentinoids with or without opioids after burn injury in the US, 2012–2018
2022, BurnsCitation Excerpt :In their study of pruritus control in the period after burn, Ahuja et al. conducted two randomized trials comparing pregabalin and gabapentin with cetirizine. Both centrally acting agents were found to significantly improve itching scores compared to cetirizine or placebo [12,13]. While more research is needed, it appears that gabapentinoids are likely to benefit a subset of burn patients; those that experience neuropathic pain, are resistant to standard therapy or receive prolonged opioid treatment.
Burn survivors’ perception of recovery after injury: A Northwest Regional Burn Model System investigation
2020, BurnsCitation Excerpt :However, many factors contribute to a burn survivor’s poor sleep, including itching [15], indicating that sleep hygiene alone might not be an adequate solution. Each patient-reported barrier to recovery represents an opportunity for clinical intervention, potentially involving multimodal or combination therapy [26–28]. In addition to identifying pain, itch, range of motion and sleep as barriers to recovery, non-whites and Hispanics shared the alarming message that access to medical care, wound care supplies, and information about their burn injuries were barriers.
Cultural adaptation of the 5-D itch scale and its reliability for Brazilian burn survivors
2019, BurnsCitation Excerpt :Apart from its high incidence, the literature has described how pruritus has a negative effect on the quality of life of burn patients [6]. Different scales have been used to assess pruritus in adult and child burn survivors, such as the Itch Man Scale [7], the 5-D itch scale [8], the visual analog scale [7,9–11], and the Questionnaire to Assess Pruritus [12]. The visual analog scale has been used the most to assess pruritus in different medical conditions, but does not address the impact of pruritus on quality of life and may fail to detect the severity of pruritus [8].
- ☆
Presented at the 15th World Congress of International Confederation of Plastic, Reconstructive & Aesthetic Surgery from 29 November to 3rd December 2009 at Delhi.