Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial.

Since 1970 surgeons have managed deep burns by surgical debridement and autografting. We tested the hypothesis that enzymatic debridement with NexoBrid would remove the eschar reducing surgery and achieve comparable long-term outcomes as standard of care (SOC). In this Phase 3 trial, we randomly assigned adults with deep burns (covering 3-30% of total body surface area [TBSA]) to NexoBrid, surgical or nonsurgical SOC, or placebo Gel Vehicle (GV) in a 3:3:1 ratio. The primary endpoint was complete eschar removal (ER) at the end of the debridement phase. Secondary outcomes were need for surgery, time to complete ER, and blood loss. Safety endpoints included wound closure and 12 and 24-months cosmesis on the Modified Vancouver Scar Scale. Patients were randomized to NexoBrid (n = 75), SOC (n = 75), and GV (n = 25). Complete ER was higher in the NexoBrid versus the GV group (93% vs 4%; P < .001). Surgical excision was lower in the NexoBrid vs the SOC group (4% vs 72%; P < .001). Median time to ER was 1.0 and 3.8 days for the NexoBrid and SOC respectively (P < .001). ER blood loss was lower in the NexoBrid than the SOC group (14 ± 512 mL vs 814 ± 1020 mL, respectively; P < .0001). MVSS scores at 12 and 24 months were noninferior in the NexoBrid versus SOC groups (3.7 ± 2.1 vs 5.0 ± 3.1 for the 12 months and 3.04 ± 2.2 vs 3.30 ± 2.76 for the 24 months). NexoBrid resulted in early complete ER in >90% of burn patients, reduced surgery and blood loss. NexoBrid was safe and well tolerated without deleterious effects on wound closure and scarring.

Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.

A Comparison of Topical Agents for Eschar Removal in a Porcine Model: Bromelain-enriched vs Traditional Collagenase Agents.

Surgical excision and grafting of deep partial-thickness (DPT) and full-thickness (FT) burns is a cornerstone of wound care. The use of commercially available topical enzymatic agents has been limited due to slower and less complete eschar removal than surgical excision. Using a porcine model of DPT and FT burns, we compared the eschar removal efficacy of a bromelain-enriched enzymatic agent derived from the stems of pineapple plants and a commercially available collagenase. We created 40 DPT and 40 FT burns on four anesthetized Yorkshire pigs. Eschar removal was initiated 24 hours later. Two pigs each were randomly assigned to collagenase or the bromelain-enriched agent. The bromelain-enriched agent was applied topically once for 4 hours followed by a 2-hour soaking. The collagenase was applied topically daily until complete removal of eschar or for up to 14 days. All bromelain-enriched treated FT burns underwent complete removal of the eschar after a single application while none of the collagenase-treated FT burns underwent complete removal of the eschar even after 14 days of treatment. All bromelain-enriched treated DPT burns had complete eschar removal after the single application. None of the collagenase-treated DPT burns experienced complete removal of eschar after 10 days; by day 14, 35% had complete eschar removal, 30% had >50% eschar removed, and 35% had <50% eschar removed. We conclude that eschar removal is quicker and more complete with the bromelain-enriched compared with collagenase debriding agent.

An open-label, proof-of-concept study assessing the effects of bromelain-based enzymatic debridement on biofilm and microbial loads in patients with venous leg ulcers and diabetic foot ulcers.

BACKGROUND: Most chronic wounds contain biofilm, and debridement remains the centerpiece of treatment. Enzymatic debridement is an effective tool in removing nonviable tissue, however, there is little evidence supporting its effect on planktonic and biofilm bacteria. OBJECTIVE: This study evaluated the effects of a novel BBD agent on removal of nonviable tissue, biofilm, and microbial loads in patients with chronic ulcers. MATERIALS AND METHODS: Twelve patients with DFU or VLU were treated with up to 8 once-daily applications of BBD and then followed for an additional 2 weeks. Punch biopsy specimens were collected and analyzed for biofilm, and fluorescence imaging was used to measure bacterial load. RESULTS: Ten patients completed treatment, and 7 achieved complete debridement within a median of 2 applications (range, 2-8). By the end of the 2-week follow-up period, the mean ± SD reduction in wound area was 35% ± 38. In all 6 patients who were positive for biofilm at baseline, the biofilm was reduced to single individual or no detected microorganisms by the end of treatment. Red fluorescence for Staphylococcus aureus decreased from a mean of 1.09 cm² ± 0.58 before treatment to 0.39 cm² ± 0.25 after treatment. BBD was safe and well tolerated. CONCLUSION: Preliminary data suggest that BBD is safe and that it can be used to effectively debride DFU and VLU, reduce biofilm and planktonic bacterial load, and promote reduction in wound size.

Development of a porcine hard-to-heal wound model: evaluation of a bromelain-based enzymatic debriding agent.

AIMS: We describe the development of a novel porcine eschar model and compare the debridement efficacy of various concentrations of a novel bromelain-based enzymatic agent with collagenase. METHODS: Full thickness excisional wounds were created on pigs and injected intradermally with various doses of doxorubicin. Wounds were monitored for a period of 46 days for the development of eschar and wound closure. After determining the optimal concentration and dose of doxorubicin resulting in non-healing eschars, these conditions were used to create additional wounds on another set of animals. The resulting eschars were treated with various concentrations of a novel bromelain-based enzymatic agent (EscharEx-02) or collagenase. The primary endpoint was greater than 95% removal of the central eschar. RESULTS: Consistent eschars composed of two distinct areas (a central area of exudate and slough representing the hard-to-heal wound bed, and a peripheral area of full-thickness mummified necrosis) were seen after injection of doxorubicin (0.5 ml/cm2 of stock solution 0.75mg/ml) at one and six days after wound creation. Complete removal of the central eschar was achieved in all wounds after five and eight treatments with 5% and 2% EscharEx-02 respectively. Complete removal of the central eschar with collagenase was achieved in 0% and 82% of the wounds after 10 and 16 treatments respectively. CONCLUSIONS: We describe a porcine model for creating eschars similar to hard-to-heal wounds in humans. A novel bromelain-based enzymatic debridement agent was more effective than a commercially available collagenase in removing eschars in this wound model.

Reducing the hospital burden associated with the treatment of pulmonary embolism.

Pulmonary embolism (PE) is the most feared clinical presentation of venous thromboembolism (VTE). Patients with PE have traditionally been treated in hospital; however, many are at low risk of adverse outcomes and current guidelines suggest outpatient treatment as an option. Outpatient treatment of PE offers several advantages, including reduced risk of hospital-acquired conditions and potential cost savings. Despite this, patients with low-risk PE are still frequently hospitalized for treatment. This narrative review summarizes current guideline recommendations for the identification of patients with low-risk PE who are potentially suitable for outpatient treatment, using prognostic assessment tools (e.g. the Pulmonary Embolism Severity Index [PESI] and simplified PESI) and clinical exclusion criteria (e.g. Hestia criteria) alone or in combination with additional cardiac assessments. Treatment options are discussed along with recommendations for the follow-up of patients managed in the non-hospital environment. The available data on outpatient treatment of PE are summarized, including details on patient selection, anticoagulant choice, and short-term outcomes in each study. Accumulating evidence suggests that outcomes in patients with low-risk PE treated as outpatients are at least as good as, if not better than, those of patients treated in the hospital. With mounting pressures on health care systems worldwide, increasing the proportion of patients with PE treated as outpatients has the potential to reduce health care burdens associated with VTE.

Emergency Department Discharge of Pulmonary Embolus Patients.

BACKGROUND: Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = -$2,999 to -$2,151). CONCLUSIONS: Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.

Development of a contaminated ischemic porcine wound model and the evaluation of bromelain based enzymatic debridement.

OBJECTIVES: There are no well accepted animal models of chronic wounds, limiting advances in understanding and treatment of chronic ulcers. We developed a porcine wound model which combines multiple factors involved in chronic wounds to create a contaminated necrotic eschar and evaluated the debriding efficacy of a novel bromelain based enzymatic debriding agent (EscharEx). METHODS: Contaminated ischemic wounds were created on the flanks of domestic pigs by 'sandwiching' the skin between 2 'O' rings (1 placed on the surface of the skin and the other underneath the skin) for 24h prior to dermatomal excision of the necrotic eschar and its contamination with Staphylococcus aureus and Candida albicans. After confirming the development of infected eschars, additional animals were used to compare the effects of daily application of topical EscharEx or its hydrating vehicle on eschar debridement as a control. RESULTS: In all cases, application of the 'O' rings resulted in full thickness necrotic ecshars with invasive infections, which did not reepithelialize and sloughed off spontaneously within 14-21 days. All wounds reepithelialized within 28-42 days forming contracted scars. All EscharEx treated eschars were completely debrided within 7-9 days, while no debridement was evident in eschars treated with the control gel. CONCLUSIONS: Our model simulates the initial phase of chronic wounds characterized by a contaminated necrotic eschar allowing evaluation of wound debriding agents, and that a bromelain-based debriding agent completely debrides the contaminated necrotic eschars within one week in this model.

A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT.

OBJECTIVES: Excisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC. METHODS: We conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4h) or SOC, which included surgical excisional or non-surgical debridement. RESULTS: NXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P<0.0001), need for surgery (24.5% vs. 70.0%, P<0.0001), the area of burns excised (13.1% vs. 56.7%, P<0.0001) and the need for autografting (17.9% vs. 34.1%, P=0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events. CONCLUSIONS: Enzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns. TRIAL REGISTRATION: Clinical Trials.gov NCT00324311.

Selectivity of a bromelain based enzymatic debridement agent: a porcine study.

BACKGROUND: Debridement of the burn eschar is a cornerstone of burn wound care. Rapid enzymatic debridement with a bromelain-based agent (Debriding Gel Dressing-DGD) has recently been investigated. The current study was designed to further investigate the selectivity of DGD to burned eschar in a larger number and more varied types of wounds. METHODS: A systematic animal experiment was conducted to determine the effects of DGD on normal, non-injured skin, burns, exposed dermis of donor sites, and skin punch biopsy wells. Partial thickness dermal burns and partial thickness skin graft donor sites were created on a pig and treated with a 4-h application of DGD or its control hydrating vehicle that does not have any activity except hydration. Punch biopsy samples were taken before and after treatment and microscopically assessed for evidence of tissue viability and its respective components thickness. RESULTS: Rapid dissolution of the burn eschar was noted in all DGD but not vehicle treated burns. There was no apparent damage to the underlying sub eschar dermis, donor sites, normal skin or punch biopsy wells after exposure to DGD. While the thickness of the treated tissues slightly increased due to edema, the increase in dermal thickness was similar after treatment with DGD or its vehicle. The increase in the cross section surface area of the treated punch biopsy wells was similar after treatment with DGD and its control vehicle. CONCLUSIONS: Exposure of the burn eschar to DGD results in its rapid dissolution. Exposure of normal skin or non-burned dermis to DGD has no effects demonstrating its selectivity to eschar.

Comparison of purified olive oil and silver sulfadiazine in the treatment of partial thickness porcine burns.

INTRODUCTION: Burns are widespread in the developed world, and expensive burn dressings are not universally available. Most burn patients suffer from a partial thickness burn that can be treated conservatively. Nevertheless, the ideal dressing for the burn wound has not been identified. We performed an animal experiment to compare the healing of partial thickness burns treated with silver sulfadiazine (SSD) and olive oil. METHODS: A randomized controlled animal experiment was conducted on 3 anesthetized domestic pigs in which 51 partial thickness burns were created using a metal bar heated to 400°C and applied to the dorsum of the animals for 20 seconds. The burns were treated every other day with SSD cream (n = 16), purified olive oil (n = 20), or no topical therapy at all (n = 15). Assessment of wound healing was done by drawing and scanning the margins of the wound at the endpoint of the experiment. The remaining open wound area was then calculated using Scion Image version beta 4.0.2 (Scion, Frederick, Md), and the results were analyzed using a 1-way ANOVA test. RESULTS: Burns treated with SSD healed faster than control burns (P < .05). There were no differences in the healing rates of wounds treated with olive oil versus controls or SSD. There were no wound infections in any of the 3 study groups. CONCLUSIONS: Treatment of partial thickness burns with purified olive oil did not result in faster healing when compared with SSD or dry gauze in a porcine model.

Reepithelialization of mid-dermal porcine burns after rapid enzymatic debridement with Debrase®.

Reepithelialization of mid-dermal burns is delayed by the presence of a layer of necrotic eschar. The authors hypothesized that rapid selective debridement using an enzymatic bromelain-based preparation, Debrase®, would speed reepithelialization. Forty mid-dermal burns (2.5 × 2.5 cm) were created on the back and flanks of two anesthetized domestic pigs (25 kg) using an aluminum bar (150 g) preheated in hot water (80°C) and applied for 20 seconds. The burns were randomized to a 4-hour topical application of Debrase® (n = 20) or its vehicle (n = 20) followed by daily application of a petrolatum-based triple antibiotic. Wounds were visualized and photographed daily for evidence of reepithelialization. Reepithelialization was considered complete when the entire wound was opaque and dry when blotted with tissue paper. 4-mm full-thickness biopsies were obtained for histological analysis using hematoxylin and eosin staining by a board-certified dermatopathologist masked to the burn therapy at 7, 9, 11, and 13 days after injury. The primary outcome was time to complete reepithelialization of the burns. Secondary outcomes were the percentage of burns that were reepithelialized at days 7, 11, and 13 and the mean percentage reepithelialization on microscopic analysis. A sample of 20 burns in each group had 80% power to detect a 2-day difference in the time to complete reepithelialization (two-tailed, P < .05). Application of Debrase®, but not the control vehicle, resulted in dissolution of the necrotic upper dermis in all treated burns. The mean time to complete reepithelialization was faster for Debrase®-treated (7.4 ± 0.8 days) than control-treated (9.1 ± 2.1 days) burns: difference, 1.7 days (95% confidence interval, 0.5-2.9). The percentage of completely reepithelialized Debrase®- and control-treated burns were day 7, 65.0 vs 25.0% (P = .02); day 9, 80.0 vs 40.0% (P = .02); and day 11, 100.0 vs 92.0% (P = .45). Treatment of mid-dermal porcine burns with a single topical application of Debrase® results in earlier wound reepithelialization.

The effects of rapid enzymatic debridement of deep partial-thickness burns with Debrase on wound reepithelialization in swine.

Reepithelialization of deep burns requires spontaneous or active removal or debridement of the necrotic eschar, as recently defined by the American Burn Association. Debrase is a bromelain-derived enzymatic preparation that has been shown to result in rapid and selective debridement of human and animal burns. The authors hypothesized that rapid debridement of deep dermal burns with Debrase would result in earlier reepithelialization of the remaining dermis in a porcine model. Eighty deep dermal contact burns measuring 10 by 20 mm were created on the back and flanks of anesthetized domestic pigs (25 kg) using a brass template preheated in boiling water (100 degrees C) that was applied to the skin for a period of 30 seconds. The template was applied using a spring-loaded device designed to control the amount of pressure applied to the skin by the template. Burns were randomized to a 4-hour topical application of Debrase (lyophilized dry enzyme dissolved and activated in a hydrating vehicle) (n = 40) or its hydrating vehicle (n = 40) followed by daily application of a petrolatum-based antibiotic ointment. Wounds were visually assessed and photographed daily. Four-millimeter full-thickness punch biopsies were obtained for histological analysis using hematoxylin and eosin staining by a board-certified dermatopathologist masked to burn therapy at 7, 11, 13, and 15 days after injury. The primary outcome was the percentage of the burns that were completely reepithelialized at each time point. Secondary outcomes were time to complete reepithelialization and the mean percentage of reepithelialization on microscopic analysis. A sample of 40 burns in each group had 80% power to detect a 20% difference in the percentage of completely reepithelialized burns (two tailed, P < .05). The percentage of completely reepithelialized burns was higher for Debrase than control burns at days 11 (40.9% vs 3.1%; P = .002), 13 (87.5% vs 50%; P = .007), and 15 (97.5% vs 77.5%, P = .018). The mean (SD) percentage reepithelialization of Debrase-treated burns at 7 days was higher than of control burns (47.6% [3.2] vs 0% [0]; P < .001). A larger number of cells in the epidermis and dermis of debrided burns stained positive for the proliferation antigen Ki-67. There was no evidence of any adverse events in the normal skin adjacent to the Debrase-treated burns. Rapid enzymatic debridement of deep partial-thickness burns with Debrase results in earlier reepithelialization and cellular proliferation in swine, when compared with carrier and topical antibiotic dressings alone.

Heat or cold packs for neck and back strain: a randomized controlled trial of efficacy.

OBJECTIVES: Acute back and neck strains are very common. In addition to administering analgesics, these strains are often treated with either heat or cold packs. The objective of this study was to compare the analgesic efficacy of heat and cold in relieving pain from back and neck strains. The authors hypothesized that pain relief would not differ between hot and cold packs. METHODS: This was a randomized, controlled trial conducted at a university-based emergency department (ED) with an annual census of 90,000 visits. ED patients >18 years old with acute back or neck strains were eligible for inclusion. All patients received 400 mg of ibuprofen orally and then were randomized to 30 minutes of heating pad or cold pack applied to the strained area. Outcomes of interest were pain severity before and after pack application on a validated 100-mm visual analog scale (VAS) from 0 (no pain) to 100 (worst pain), percentage of patients requiring rescue analgesia, subjective report of pain relief on a verbal rating scale (VRS), and future desire for similar packs. Outcomes were compared with t-tests and chi-square tests. A sample of 60 patients had 80% power to detect a 15-mm difference in pain scores. RESULTS: Sixty patients were randomized to heat (n = 31) or cold (n = 29) therapy. Mean (+/-standard deviation [SD]) age was 37.8 (+/-14.7) years, 51.6% were female, and 66.7% were white. Groups were similar in baseline patient and pain characteristics. There were no differences between the heat and cold groups in the severity of pain before (75 mm [95% CI = 66 to 83] vs. 72 mm [95% CI = 65 to 78]; p = 0.56) or after (66 mm [95% CI = 57 to 75] vs. 64 mm [95% CI = 56 to 73]; p = 0.75) therapy. Pain was rated better or much better in 16/31 (51.6%) and 18/29 (62.1%) patients in the heat and cold groups, respectively (p = 0.27). There were no between-group differences in the desire for and administration of additional analgesia. Twenty-five of 31 (80.6%) patients in the heat group and 22 of 29 (75.9%) patients in the cold group would use the same therapy if injured in the future (p = 0.65). CONCLUSIONS: The addition of a 30-minute topical application of a heating pad or cold pack to ibuprofen therapy for the treatment of acute neck or back strain results in a mild yet similar improvement in the pain severity. However, it is possible that pain relief is mainly the result of ibuprofen therapy. Choice of heat or cold therapy should be based on patient and practitioner preferences and availability.

Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis.

Deep burns are associated with the formation of an eschar, which delays healing and increases the risk of infection. Surgical debridement of the eschar is, at present, the fastest means to achieve an eschar-free bed, but the process can not differentiate between the viable tissue and the eschar and follow the minute irregularities of the interface between the two. We evaluated the efficacy and selectivity of a novel enzymatic bromelain-based debriding agent, Debrase Gel Dressing (Debrase), in a porcine comb burn model. We hypothesized that Debrase would result in rapid debridement of the eschar without adverse effects on the surrounding uninjured skin. This is a prospective, controlled, animal experiment. Five domestic pigs (20-25 kg) were used in this study. Sixteen burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20 mm full-thickness burns and separated by three 5 x 20 mm unburned interspaces representing the zone of stasis. The burned keratin layer (blisters) was removed, and the burns were treated with a single, topical, Debrase or control vehicle application for 4 hours. The Debrase/control was then wiped off using a metal forceps handle, and the burns were treated with a topical silver sulfadiazine (SSD). The wounds were observed, and full-thickness biopsies were obtained at 4 and 48 hours for evidence of dermal thickness, vascular thrombosis, and burn depth, both within the comb burns and the unburned interspaces in between them. Chi-square and t tests are used for data analysis. A single 4-hour topical application of Debrase resulted in rapid and complete eschar dissolution of all the burns in which the keratin layer was removed. The remaining dermis was thinner (1.1 +/- 0.7 mm) than in the control burns (2.1 +/- 0.3 mm; difference 0.9 mm [95% confidence interval: 0.3-1.4]) and was viable with no injury to the normal surrounding skin or to the unburned interspaces between the burns, which represents the zone of stasis. In control burns, the entire thickness of the dermis was necrotic. At 48 hours, Debrase-treated areas were found partially desiccated under SSD treatment. The unburned interspaces demonstrated partial-thickness necrosis in two third and full-thickness necrosis in one third of wounds. In contrast, full-thickness necrosis was noted in all control interspaces (P = .05). In a porcine comb burn model, a single, 4-hour topical application of Debrase resulted in rapid removal of the necrotic layer of the dermis with preservation of unburned tissues. At 48 hours, SSD treatment resulted in superficial tissue damage and partial preservation of the unburned interspaces.

Combined ultrasonic and enzymatic debridement of necrotic eschars in an animal model.

Several methods are used to debride burn eschars, however, most are ineffective for ischemic eschars. We investigated a novel combination of enzymatic and ultrasonic debridement for ischemic eschars. A previously described ischemic flap model in rats was used to compare the time to flap debridement or perforation of enzymatic (Debrase, a derivative of bromelain), ultrasonic, or combined debridement (Hybrid Debridement Technology). We also evaluated the effects of ultrasonic intensity, probe size, probe housing, and operation mode (pulsatile vs. continuous) on the time to full eschar perforation. Ultrasonic and enzymatic debridement alone did not result in flap perforation even after 15 minutes. Combined ultrasonic and enzymatic debridement resulted in flap perforation within 2 to 5 minutes in the four flap zones (P < 0.001 for all four flap zones compared with ultrasound alone). The most rapid debridement was observed with an ultrasonic intensity of 3.2 W/cm, applied using a 4.9 cm probe. The temperature elevation associated with ultrasonication was controlled by perfusion of fresh Debrase solution and alternating the ultrasound energy. Combination of ultrasonic and enzymatic debridement of ischemic flap eschars in rats with Debrase is more rapid and effective than either method alone.

Warm lidocaine/tetracaine patch versus placebo before pediatric intravenous cannulation: a randomized controlled trial.

STUDY OBJECTIVE: We compare the pain of intravenous (IV) cannulation in pediatric emergency department (ED) patients after applying a topical lidocaine/tetracaine patch versus placebo. We hypothesized that application of the active patch would reduce the pain of IV cannulation by at least 15 mm. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in a suburban academic ED. Patients aged 3 to 17 years who required nonemergency IV cannulation were eligible for enrollment. At triage, a nurse placed a commercially available topical lidocaine/tetracaine patch or an identical-looking placebo patch over the antecubital or hand vein in patients for whom an IV catheter was anticipated. After IV cannulation by the treating nurse, the pain of cannulation was measured on a validated 100-mm visual analogue scale or Wong Baker scale. Outcomes were compared between groups with Mann-Whitney U, Student t, and chi(2) tests. A sample of 40 patients had 80% power to detect a 13-mm difference in pain scores. RESULTS: Forty-five patients were randomized to lidocaine/tetracaine patch (22) or placebo (23), and IV cannulation was attempted in 40 of these patients. Mean age was 10 years (SD=4.3), 35% were female patients. The median pain of IV cannulation in the active treatment group (18 mm [interquartile range (IQR) 1 to 40 mm]) was significantly lower than in the placebo group (35 mm [IQR 20 to 59 mm]; P=.04). Adequate pain relief was more common in the active treatment group (75% [95% confidence interval (CI) 53% to 89%] versus 35% [95% CI 18% to 57%]; difference 40% [95% CI 6% to 64%]). The number of successful IV cannulations after the first attempt was similar in both the lidocaine/tetracaine and the placebo groups (90% [95% CI 70% to 97%] versus 85% [95% CI 64% to 95%]; difference 5% (95% CI -21% to 30%). CONCLUSION: Application of a topical lidocaine/tetracaine patch resulted in a modest reduction in the pain of IV cannulation in pediatric ED patients and did not alter the rate of successful cannulations.

Curcumin reduces burn progression in rats.

OBJECTIVES: Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. METHODS: This was a randomized controlled experiment. Twenty Sprague-Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20-mm full-thickness burns separated by three 5 x 20-mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full-thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi-square tests. RESULTS: Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full-thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. CONCLUSIONS: Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.

Digital versus local anesthesia for finger lacerations: a randomized controlled trial.

OBJECTIVES: To compare the pain of needle insertion, anesthesia, and suturing in finger lacerations after local anesthesia with prior topical anesthesia with that experienced after digital anesthesia. METHODS: This was a randomized controlled trial in a university-based emergency department (ED), with an annual census of 75,000 patient visits. ED patients aged > or = 8 years with finger lacerations were enrolled. After standard wound preparation and 15-minute topical application of lidocaine-epinephrine-tetracaine (LET) in all wounds, lacerations were randomized to anesthesia with either local or digital infiltration of 1% lidocaine. Pain of needle insertion, anesthetic infiltration, and suturing were recorded on a validated 100-mm visual analog scale (VAS) from 0 (none) to 100 (worst); also recorded were percentage of wounds requiring rescue anesthesia; time until anesthesia; percentage of wounds with infection or numbness at day 7. Outcomes were compared by using Mann-Whitney U and chi-square tests. A sample of 52 patients had 80% power to detect a 15-mm difference in pain scores. RESULTS: Fifty-five patients were randomized to digital (n = 28) or local (n = 27) anesthesia. Mean age (+/-SD) was 38.1 (+/-16.8) years, 29% were female. Mean (+/-SD) laceration length and width were 1.7 (+/-0.7) cm and 2.0 (+/-1.0) mm, respectively. Groups were similar in baseline patient and wound characteristics. There were no between-group differences in pain of needle insertion (mean difference, 1.3 mm; 95% confidence interval [CI] = -17.0 to 14.3 mm); anesthetic infiltration (mean difference, 2.3 mm; 95% CI = -19.7 to 4.4 mm), or suturing (mean difference, 7.6 mm; 95% CI = -3.3 to 21.1 mm). Only one patient in the digital anesthesia group required rescue anesthesia. There were no wound infections or persistent numbness in either group. CONCLUSIONS: Digital and local anesthesia of finger lacerations with prior application of LET to all wounds results in similar pain of needle insertion, anesthetic infiltration, and pain of suturing.

Laser-assisted anesthesia reduces the pain of venous cannulation in children and adults: a randomized controlled trial.

OBJECTIVES: Application of topical anesthetics before intravenous (IV) cannulation is effective yet limited by delayed transdermal absorption. The authors evaluated a handheld laser device to enhance topical anesthetic absorption by ablating the stratum corneum, the major barrier to drug absorption through the skin. The hypothesis was that laser-assisted anesthesia would reduce the pain of IV cannulation in emergency department (ED) patients. METHODS: This was a blinded, randomized, controlled trial. ED patients aged 1 year and older requiring nonemergent IV cannulation were included. Patients were randomized to pretreatment of the skin with laser or sham laser, and standardized venous cannulation was performed on the dorsum of the patients' hands or antecubital fossa. In the experimental group, the area over the target vein was pretreated with a lightweight, portable Er:YAG unit, with a fluence of 3.5 J/cm2, a pulse width of 600 microseconds, and a spot diameter of 6 mm. Lidocaine 4% cream was applied to the area immediately after laser application. Five minutes later, the cream was wiped off and a trained nurse inserted an IV catheter. In the control group, a sham laser and lidocaine were used. Pain of laser application and IV cannulation was recorded on age-appropriate pain scales; presence of infection or abnormal pigmentation was determined at one week. Pain of cannulation was compared using parametric and nonparametric tests. RESULTS: Sixty-one patients were randomized to laser (30) and sham (31) pretreatment. Mean (+/- SD) age was 27 (+/- 21) years, 49% were female, and one half were children younger than 18 years. The mean pain of IV cannulation was significantly less (mean difference, 28.3 mm; 95% confidence interval = 17.9 to 38.7) in patients pretreated with the laser (10.0 mm; 95% confidence interval = 4.4 to 15.6) than with sham laser (38.3 mm; 95% confidence interval = 29.3 to 42.2). The difference in children was also significant. Application of the laser was painless in most patients. No patient developed infection or abnormal pigmentation. CONCLUSIONS: Pretreatment of the skin with a laser device followed by a five-minute topical lidocaine 4% application reduces the pain of IV cannulation in ED adult and pediatric patients.