pregabalin and Burns

Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus.

Topics: Animals; Antipsychotic Agents; Burns; Gabapentin; Histamine Antagonists; Humans; Inflammation; Keratinocytes; Narcotic Antagonists; Neuropeptides; Ondansetron; Pregabalin; Pruritus; Receptors, Opioid; Wound Healing

The primary objective of the study was to evaluate the efficacy of 300 milligrams (mg) and 600 mg of pregabalin compared to placebo in the reduction of pain in patients with noncritical partial and full thickness burn injuries.. A prospective, randomized, double-blinded, single center, placebo-controlled trial was conducted. Simple randomization method was used in this trial. After subjects met all the inclusion and none of the exclusion criteria, they were randomized and assigned to 1 of the 3 18-day treatments groups: Pregabalin 300 group, Pregabalin 600 group, or Placebo group. Demographics and clinical characteristics were recorded. The severity of pain was assessed by using the visual analog scale for pain intensity at baseline on day 3, day 9 ± 3, day 25 ± 7, day 90 ± 6, and day 180 ± 12.. A total of 54 subjects were randomly assigned, and 51 were included in the data analysis. Demographics and clinical characteristics did not differ significantly between the 3 groups. There was a statistically significant difference in pain between the Pregabalin 300 and Pregabalin 600 groups (P-value = .0260). The Pregabalin 300 group had 17.93 units (95% confidence interval: 1.83-34.04) higher pain scores on average than the Pregabalin 600 group, regardless of time. The adjusted P-value comparing 0 to 300 was .1618, while the adjusted P-value for 0 versus 600 was .5304. There was an overall difference in pain across time regardless of study group (P-value = <.0001). An overall difference in opioid consumption (P-value = .0003) and BSHS (P-value = .0013) across time regardless of study group was noted.. Pregabalin could be part of a promising multimodal analgesic regimen in noncritical burn population. Future placebo-controlled studies assessing the use of pregabalin in burn victim patients may further endorse our findings.

Topics: Adult; Analgesics; Analgesics, Opioid; Burns; Combined Modality Therapy; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebos; Pregabalin; Prospective Studies; Treatment Outcome; Visual Analog Scale

Post-burn itch is a distressing symptom in burns rehabilitation and its treatment often proves frustrating for the patient and the multidisciplinary burns team. Traditionally, the mainstay of antipruritic therapy for decades has been antihistamines and massage with emollients. With a better understanding of the neurophysiology of itch emerged a new dimension in the treatment of post-burn pruritus. Gabapentin, a centrally modulating anti-epileptic agent and α2δ ligand, proved in clinical trials to be immensely better in the treatment of post-burn pruritus. Pregabalin is a newer structural analog of gabapentin. It has a much better anxiolytic effect and pharmacokinetic profile as compared to gabapentin. The current study was initiated to specifically study the role of pregabalin in relieving post-burn itch as this has never been investigated before. This double blind, randomized and placebo controlled study had four arms and was carried out on 80 adult patients (20 each). The four arms were: pregabalin, cetirizine with pheniramine maleate, combination of pregabalin, cetirizine and pheniramine maleate, and placebo (vit. B comp.). Massage with coconut oil was integral to all groups. Drug dosage was determined by initial VAS (visual analog scale) scores. All groups matched in demographic data and initial VAS scores. VAS scores were evaluated over next 28 days (days 3, 7, 14, 21 and 28). In patients with mild itch (VAS scores 2-5) or moderate itch (VAS scores 6-8) near complete remission of itch was seen in combination group and pregabalin group where the response was comparable and close to 95%. This was significantly better response than antihistaminic combination or massage alone. However, massage alone was sufficient in decreasing mean scores in mild itch, in a large percentage of patients. Amongst the patients with severe itch (VAS scores 9-10), 3/6 and 6/7 patients dropped out of trial in the antihistaminic and placebo groups, respectively. Combination therapy and pregabalin alone had exactly similar decrease in itch scores by day 28 (78.9%). This far exceeded the response in the antihistaminic and placebo groups (23.9% and 9.2% respectively). We conclude that moderate to severe pruritus (VAS 6-10) should be treated with a systemic, centrally acting agent like pregabalin or gabapentin to eliminate itch or bring it down to tolerable limits. Patients with mild itch having VAS scores between 4 and 5 may be better served with addition of pregabalin even if ma

Topics: Adult; Analgesics; Anti-Allergic Agents; Burns; Cetirizine; Coconut Oil; Double-Blind Method; Female; gamma-Aminobutyric Acid; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Pain Measurement; Pheniramine; Plant Oils; Pregabalin; Pruritus; Severity of Illness Index; Young Adult

This randomised, double-blind, placebo-controlled trial assessed the efficacy and tolerability of pregabalin to alleviate the neuropathic component of moderate to severe burn pain. Patients aged 18 to 65 years admitted to a burns unit with a 5% or greater total body surface area burn injury were screened to participate in the trial. Using the Neuropathic Pain Scale (NPS), patients scoring 4 or higher on 'hot' pain or 'sharp' pain were invited to participate. Consenting patients were randomly assigned to receive pregabalin or placebo for 28 days with individual dose titration commencing at 75 mg twice daily to a maximum pregabalin dose of 300 mg twice daily. The primary outcome measure was the patients' daily response to the sharp and hot pain of the NPS. Secondary outcome measures included the remaining elements of the NPS, daily opioid requirement, length of hospital stay, pain at 6 months, and side effects of nausea, vomiting, drowsiness and giddiness. For patients administered pregabalin, the primary outcome measures hot (P = .01) and sharp (P = .04) pain were significantly reduced compared with those in patients administered placebo. Secondary outcome measures of itch, unpleasantness, surface pain, and procedural pain were significantly lower (P < .05) in the pregabalin group. Adverse effects were uncommon, with no difference between the treatment groups. There was no significant difference between the pregabalin and placebo treatment groups with respect to opioid consumption, duration of hospital stay, or pain at 6 months. Pregabalin was efficacious and well tolerated in patients after severe burn injury and whose pain was characterised by features of acute neuropathic pain. In this study, pregabalin was well tolerated and significantly reduced several elements of the neuropathic pain scale including hot pain, unpleasantness of the pain, surface pain, and itch, and also significantly reduced procedural pain.

Topics: Adolescent; Adult; Aged; Analgesics; Analgesics, Opioid; Burns; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Time Factors; Treatment Outcome; Young Adult

Severe burn patients undergo prolonged administration of sedatives and analgesics for burn care. There are currently no guidelines for the dose adaptation of sedation-analgesia in severe burn patients.. We performed a before-after 2-center study to demonstrate the feasibility and efficacy of a sedation-analgesia scale-based protocol in severely burned patients receiving ≥24h of invasive mechanical ventilation. Before the intervention, continuous infusion of hypnotic and morphine derivatives was continued. During the Intervention phase, general anesthesia was relayed from day 1 by RASS/BPS-titrated continuous infusion of hypnotic and morphine derivatives and with short half-life drugs adminstered for daily burn dressings. The primary outcome was the duration of invasive mechanical ventilation in the ICU.. Eighty-seven (46.2%) patients were included in the Control phase and 101 (53.7%) in the Intervention phase. The median burned cutaneous surface was 20% [11%-38%] and median ABSI was 7 [5-9]. The durations of hypnotic and opioid infusions were not statistically different between the 2 phases (8 days [2-24] vs. 6 days [2-17] (P=0.3) and 17 days [4-32] vs. 8 days [3-23] (P=0.06), respectively). The duration of mechanical ventilation was 14 days [3-29] in the Control phase and 7 days [2-24] in the Intervention phase (P=0.7). When taking into account the competition between mortality and weaning from mechanical ventilation, we found no significant difference between the 2 phases (Gray test, P=0.4). The time-series analysis showed no difference for the duration of mechanical ventilation in the Intervention phase (P=0.6). Eighteen (20.7%) patients died in the Control phase, and 18 (18%) in the Intervention phase (P=0.6).. Scale-based lightening of continuous sedation-analgesia with repeated short general anesthesia for dressing is feasible in severe burn patients but failed to demonstrate a decrease in the duration of invasive mechanical ventilation.

Topics: Adult; Analgesics, Opioid; Burns; Clinical Protocols; Controlled Before-After Studies; Dose-Response Relationship, Drug; Feasibility Studies; Female; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Ketamine; Male; Midazolam; Middle Aged; Nurses; Oxycodone; Pain; Pain Management; Pain Measurement; Pain, Procedural; Pregabalin; Remifentanil; Respiration, Artificial; Time Factors; Ventilator Weaning

Pruritis after burn is one of the most common chronic complaints in burn survivors. Pruritus is often indistinguishable from neuropathic pain. There is a paucity of studies reporting the use of gabapentin and pregabalin to treat both pruritus and neuropathic pain. The purpose of this current study is to explore and document the effect of gabapentin and pregabalin in children and adolescent burn survivors.. A retrospective review of charts and pharmacy records of gabapentin and pregabalin dispensed to control pruritus and/or pain was conducted for burn survivors up to 20 years of age. Data collected included medication doses, age and weight of patients, presence of neuropathic pain and pruritus, reported response to medication, and side effects of these medications. 136 individuals who received gabapentin, pregabalin, or both medications are included in the study. 112 received only gabapentin, none received only pregabalin, and 24 received both. All results are documented in mean±standard deviation (s.d.) dose/kg/day. 104 individuals experienced pruritus exclusively, two experienced neuropathic pain exclusively, and 30 experienced both. Use of medications was considered effective if the individuals reported pruritus or pain relief from the medication. The medication was considered safe if the individuals did not experience adverse side effects warranting discontinuation of the drugs. Medications were continued with dose adjustments if an individual reported minor side effects such as sedation or hyperactivity.. The average effective dose mg/kg/day for gabapentin and pregabalin was calculated for each of the three age groups (≤5years, 6-12 years, and >12years). The average effective dose of gabapentin was 23.9±10.3mg/kg/day for children ≤5years, 27.0±15.3mg/kg/day for children 6-12 years, and 34.1±15.7mg/kg/day for children >12years. The average effective dose of pregabalin was 6.5±3.5mg/kg/day for children 6-12 years and 4.7±1.6mg/kg/day for children >12years. One 5-year-old child received 3.7mg/kg/day of pregabalin. Note that for all patients in this study, pregabalin was added after an inadequate response to gabapentin. For individuals receiving both gabapentin and pregabalin, the maximum gabapentin failure dose for pruritus was 32.8±18.0mg/kg/day and for both pain and pruritus was 28.1±18.3mg/kg/day. For individuals treated with only gabapentin, 91.4% had an adequate response for pruritus, 100% for neuropathic pain, and 43.3% for both pruritus and pain. 100% of individuals treated with both gabapentin and pregabalin had an adequate response for pruritus and 88.2% had an adequate response for both pruritus and pain. Gabapentin was associated with hyperactivity in two individuals, and sedation in one individual. One individual reported nausea, vomiting, and headaches when taking both medications; this resolved when gabapentin was discontinued. One individual reported sedation while taking both medications.. Gabapentin and pregabalin are effective in relieving pruritus and neuropathic pain in most burn survivors. In some instances, these medications can be given together. Few individuals reported side effects.

Topics: Adolescent; Analgesics; Burns; Child; Child, Preschool; Female; Gabapentin; Humans; Infant; Male; Neuralgia; Pain Measurement; Pregabalin; Pruritus; Retrospective Studies; Young Adult

Burn survivors have described a type of pain, usually after wound healing, that has characteristics of neuropathic pain. This pain is not well treated with conventional medications. Pregabalin has had reported success in treating diabetic and post-herpetic neuropathic pain. We report our experience with pregabalin for the treatment of post-burn neuropathic pain. A retrospective review of patients treated with pregabalin in a burn outpatient clinic was undertaken. A numerical pain scale was administered to each patient prior to and after treatment to determine efficacy. Side effects and reasons for discontinuation were noted. Out of 24 patients 4 patients were lost to followup, 5 patients discontinued taking pregabalin and 2 patients had incomplete data for evaluation. Of the remaining 13 patients, 69% (11) had a reduction in pain score after treatment. In addition, 2 of the patients who discontinued use had a pain score which decreased to 0. Pregabalin is a well-tolerated, effective means of treating post-burn neuropathic pain. Time to achieve effective dosing is relatively quick and there is a range of dosing available. The mechanism, pharmacokinetic benefits, and potential benefits are discussed. Further studies will be needed to look effects on quality of life and reduction of opioid use.

Topics: Analgesics; Burns; Dose-Response Relationship, Drug; Female; gamma-Aminobutyric Acid; Humans; Male; Neuralgia; Pain Measurement; Pregabalin

Gabapentin is an anticonvulsant that may represent a novel class of drugs, which has novel spinal antihyperalgesic activity. We sought to characterize this spinal action in a model of hyperalgesia that involves a mild thermal injury to the hind paw of the rat. Rats were prepared with chronic spinal catheters. Under brief halothane anesthesia, a thermal injury was induced by applying the left hind paw to a thermal surface (52.5 degrees C) for 45 s. This exposure results in mild erythema but no blistering. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus with which response latencies of the injured and uninjured (normal) paw could be obtained. Thirty minutes after thermal injury, the response latency in all groups decreased from 10-12 s to 5-7 s. Uninjured paw withdrawal latency was unaltered. The intrathecal injection of gabapentin (30-300 microg) produced a dose-dependent reversal of the hyperalgesia but had no effect on the response latency of the normal hind paw, even at the largest doses. A similar reversal was observed after intrathecal delivery of the structural analog S(+)-3-isobutyl gamma-aminobutyric acid (GABA) (30-300 microg), but not after the largest dose of its stereoisomer R(-)-3-isobutyl GABA (300 microg). The effects of both intrathecal gabapentin and S(+)-3-isobutyl GABA were reversed by intrathecal D-serine, but not L-serine. All effects were observed at doses that had no significant effect on motor function. These observations, in conjunction with the accumulating data on binding and transmitter release, emphasize that these gabapentinoids can selectively modulate the facilitation of spinal nociceptive processing otherwise generated by persistent small afferent input generated by tissue injury.. Gabapentin and its analog, 3-isobutyl gamma-aminobutyric acid, given spinally, produce a dose-dependent, D-serine-sensitive reversal of the thermal hyperalgesia evoked by mild thermal injury.

Topics: Acetates; Amines; Animals; Anticonvulsants; Burns; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Gabapentin; gamma-Aminobutyric Acid; Hyperalgesia; Injections, Spinal; Male; Pain; Pregabalin; Rats; Rats, Sprague-Dawley; Reflex; Serine; Stereoisomerism; Structure-Activity Relationship

Gabapentin (GBP) and S(+)-3-isobutyl-gamma-aminobutyric acid (IBG) are anticonvulsant agents which are effective against many clinical and experimental neuropathic pain states. We examined the efficacy of these agents in a new rat model of secondary mechanical hyperalgesia generated by a mild thermal injury. Under brief halothane anesthesia, an injury was induced by applying one heel to a hot surface (52.5 degreesC) for 45 s. GBP, IBG or saline was injected i.p. just prior to the injury. Mean mechanical withdrawal threshold (MWT) was determined using von Frey hairs before and at 30 min intervals for 3 h following the injury. MWT outside the injury area decreased post-injury (secondary hyperalgesia, allodynia), but primary (site of injury) mechanical hyperalgesia was not observed. Secondary hyperalgesia exhibited a tendency toward recovery over time. Time to onset of the anti-allodynic effect of GBP was 30-60 min. The minimum effective GBP dose was 100 mg/kg; 300 mg/kg GBP totally inhibited the drop in MWT, but was accompanied by pronounced sedation. Anti-allodynic effects of IBG were apparent at the first post-injury measure of MWT (30 min). Thirty milligrams per kilogram was the minimum effective dose; 100 mg/kg IBG totally blocked the allodynia with minimal side effects. Our findings demonstrate a dose-dependent blockade of the mechanical sensitivity caused by a mild thermal injury by both GBP and IBG. Results indicate that IBG is more effective than GBP in this model at doses which do not cause sedation. These observations support the suggested use of these or related gamma-amino acid analogues as an effective treatment for post-operative pain.

Topics: Acetates; Amines; Animals; Anticonvulsants; Burns; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Gabapentin; gamma-Aminobutyric Acid; Hyperalgesia; Injections, Intraperitoneal; Male; Pain Threshold; Pregabalin; Rats; Rats, Sprague-Dawley