Elsevier

Burns

Volume 37, Issue 2, March 2011, Pages 203-207
Burns

A comparative analysis of cetirizine, gabapentin and their combination in the relief of post-burn pruritus

https://doi.org/10.1016/j.burns.2010.06.004Get rights and content

Abstract

Post-burn pruritis is a very distressing symptom having a reported incidence between 80 and 100%. The mainstay of management of post-burn itch has been with antihistaminics and emollients but the treatment is ineffective in a very large percentage of patients. With the recognition of a distinct itch specific neuronal pathway, which has a complex interaction with pain pathway, a fresh approach to itch management has surfaced with the use of gabapentin. Gabapentin is an antiepileptic drug which has been successfully used to manage neuropathic pain, and is reporting to be successful in management of all forms of itch. With a paucity of randomized trials evaluating the role of gabapentin in post-burn itch management the current study was undertaken to individually evaluate gabapentin, cetirizine and their combination in relieving itch. Twenty patients were randomly recruited in each of the three groups and administered the respective drug(s) in doses determined by initial VAS (visual analog scale) scores. 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. VAS scores were evaluated over next 28 days (days 3, 7, 14, 21 and 28), and no emollients were prescribed for the study period. The initial mean VAS score reduced 95% in gabapentin group compared to 52% for the cetirizine group, which was highly significant (p < 0.01). There was a 94% reduction in mean VAS score in the combination group which was comparable to the relief observed with gabapentin alone (p > 0.05). Even the onset of action with gabapentin was significantly faster than the cetirizine group as evident from the mean VAS scores on day 3, which decreased 74% in gabapentin group compared to 32% in cetirizine group (p < 0.01). Whereas all patients receiving gabapentin (either as monotherapy or in combination with cetirizine) reached an itch free status (VAS score 0–1) by day 28 only 3/20 patients reached this level with cetirizine alone. It is quite evident from this study that gabapentin is significantly better than cetirizine as monotherapy in relieving post-burn itch and it also has a faster action. The hypothetical combination of a centrally acting drug with a peripherally acting agent did not result in any better control of post-burn itch than monotherapy with gabapentin. No side effects were reported with gabapentin administration but all patients receiving cetirizine reported sedation. There is now a need to relook at the antipruritic protocols in burn management.

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.

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