Lasers in Wound Healing

Introduction This month we will examine the evidence on laser stimulation of healing. While the conclusions may not all be “goodness and light,” there are areas where efficacy seems promising and some where evidence of efficacy is clearly lacking. Come with me, into the realm of “light wave amplification by stimulated emission of radiation.” We shall explore together evidence of what lasers do and may not do and which of their effects remain to be “enlightened” by properly powered, blinded, randomized, controlled, scientific studies. For those of you who wish to read full text of the articles cited, you may access them online through www.ncbi.nlm.nih.gov/PubMed/, the PubMed site for searching MEDLINE and other reference databases. Full text of these two publications can be read or printed after displaying a search on “wound clinical controlled study laser.” Select the articles that interest you by clicking on the box near the reference number. From the “Display” drop down box, select “Abstract” then click “Display.” If full text of the abstract’s article is available, the journal logo or “Full Text” link will appear above the article title. Click this with Adobe Acrobat (available free online) enabled and follow instructions at the journal site to download the PDF version of the article. This is one of many sites where the evidence “lives.” Laser Stimulation of Healing: A Systematic Cochrane Review Reference: Cullum N, Nelson EA, Flemming K, Sheldon T. Systematic reviews of wound care management: (5) beds; (6) compression; (7) laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy. Health Technol Assess 2001;5(9):1–221. Rationale: A systematic review of the literature was conducted as part of the Cochrane initiative to encourage evidence-based medical practice. Objective: Determine the conditions and indications for which laser stimulation is an effective wound therapy. Methods: A systematic literature review of 19 electronic databases, including MEDLINE, CINAHL, and EMBASE databases, was conducted pre- and including 2001. The search was supplemented to include references from additional journals, conference proceedings, and the Cochrane Controlled Trials Register. Results: All but four of the 30 studies identified were excluded from the review, due to methodology issues, such as unconcealed assignment to treatment groups, nonblinded outcomes assessment, and failure to measure outcomes. All four studies qualifying for systematic review were on venous ulcers: two on HeNe laser (both 4 J/cm2), one on GaAs (1.9 J/cm2), and one, which failed to report baseline ulcer characteristics, used an unspecified laser stimulation source combined with infrared light stimulation. None of the three trials applying laser stimulation alone, taken singly, or pooled supported a significant effect of lasers on venous ulcer healing. In the fourth study, laser plus infrared light healed 12 of 15 patients (80%), significantly more than the 5 of 15 (33%) healed in the four-week stimulation period using noncoherent red light. A third arm of the study applying laser alone reported 10 of 15 (66%) healed but did not differ from either of the other two groups, so the contribution of laser stimulation to the effect is not clear. Conclusions: The authors concluded that there is generally insufficient reliable evidence to draw conclusions about the effect of laser therapy on chronic wound healing. Laser-Assisted Penetration of Topical Anesthetic Reference: Baron E, Harris L, Redpath WS, et al. Laser-assisted penetration of topical anesthetic in adults. Arch Dermatol 2003;139:1288–90. Rationale: Erbium:YAG (Er:YAG) lasers wavelength (2940nm) is near the absorption peak of water (3000nm). As a result, its stimulation is readily absorbed by the epidermis, rendering it useful in removing target areas of stratum corneum while leaving the rest of the epidermis intact. Since the stratum corneum is the primary barrier to percutaneous penetration of topical anesthetics, its laser removal may provide a simple, painless technique for enhancing delivery of topical anesthetics. Objective: Determine the efficacy and safety of Er:YAG laser ablation of skin stratum corneum followed by topical application of four-percent lidocaine cream in reducing needle-stick pain. Methods: Two independent, multicenter, randomized, cross-over, controlled trials of 160 patients each explored the comparative efficacy and safety of laser ablation of the stratum corneum followed by 0.5mL topical four-percent lidocaine cream on one arm versus laser ablation followed by placebo on the other arm (double-blind Trial 1) or a study of laser treatment followed by topical four-percent lidocaine cream on one arm versus four-percent lidocaine cream alone on the other arm (nonblind Trial 2). Laser ablation consisted of a single, painless 250mJ pulse with the Er:YAG laser delivered to an area of 3 mm2 on the deltoid area of the arm, followed by placebo or anesthetic cream in Trial 1, then wiped off after five minutes. Patient-reported pain was measured using a 100mm visual analogue scale to rate the pain of inserting a 5/8-inch, 25-gauge needle. Side effects were evaluated 48 hours later by telephone interview. Results: Laser pretreatment significantly reduced pain of needle insertion and increased anesthesia induction versus placebo topical anesthetic in Trial 1 and versus four-percent lidocaine alone without pretreatment in Trial 2. Ten patients reported mild pain or erythema 48 hours post treatment, with no association observed between Er:YAG laser use and self-reported adverse events. Conclusions: Ablation of the stratum corneum with an Er:YAG laser in preparation for topical application of anesthetic appears to be a safe, effective means to reduce pain from needle sticks. Clinical Perspective Laser ablation of the stratum corneum enhances penetration of medications, such as topical anesthetics, but direct use of lasers to heal wounds or alleviate pain has not proven effective. A PubMed MEDLINE search of the more recent literature revealed several small trials reporting significant effects of low-level lasers stimulation on keloid or hypertrophic scar regression,1 increased forefoot skin temperature in diabetic patients with microangiopathy,2 and reduced carpal tunnel syndrome pain.3 A Cochrane systematic review of laser pain reduction for lateral elbow pain or tennis elbow concluded that higher powered, more methodologically sound trials are necessary before the conclusion can be justified that lasers are efficacious in directly relieving pain.4 An additional Cochrane review of laser therapy for venous ulcers was just published5 confirming the conclusion of the first article reviewed in this Evidence Corner that more research is needed to support a conclusion of healing efficacy for venous ulcers. In conclusion, though laser use to remove the skin’s stratum corneum may enhance penetration of medication through the skin, direct effects on wound healing or pain relief require more and better evidence for their support.