Key Insights On Using Medications In Wound Care

When it comes to patients with wounds, medications and supplements may help abate the pain and spur healing. These expert panelists discuss key considerations with the use of supplements and pharmaceuticals for wound pain and neuropathic wounds.

Q: What medications or supplements do you use for wound pain?

A: For Kazu Suzuki, DPM, CWS, appropriate wound debridement and applying a moist wound dressing are the most important keys in managing wound pain. For wound pain associated with debridement, Lee C. Rogers, DPM, suggests applying topical lidocaine gel or lidocaine soaked gauze. If this is insufficient, he says injecting an anesthetic in the periulcerative area or performing debridement in the OR can mitigate the pain.

   If the wound pain results from a dressing change, Dr. Rogers uses a non-adherent dressing such as Mepilex or Mepitel (Molnlycke) with Safetac silicone technology. He says an alternative would be soaking the dressing with an anesthetic prior to removal. For patients with pain due to VAC therapy (KCI) dressing changes, he notes one can turn off the suction, infiltrate the foam with lidocaine and let it set for a few minutes.

   Kathy Satterfield, DPM, says there is often a misperception that all wound patients are insensate but notes this is obviously not always the case. She treats patients’ wound pain “very aggressively,” often doing so in concert with physicians at pain clinics.

   If patients do not have pain relief with a hydrocodone/acetaminophen tablet (Vicodin, Abbott Laboratories) on a TID to QID basis, Dr. Satterfield refers them to a pain clinic. If the patient needs an additional modality such as a fentanyl patch for pain management, she defers to the pain management specialist.

   “It is good for referrals. It is good practice. It is just good medicine,” she notes.

   When it comes to pain medication, Dr. Suzuki uses an escalating approach that he learned from a pain management doctor. He will start with acetaminophen (Tylenol, McNeil) 1,000 mg four times a day. If this is not effective, Dr. Suzuki will consider hydrocodone/acetaminophen 5/500, 7.5/750, 10/660. If the pain continues unabated, he will consider oxycodone/acetaminophen (Percocet, Endo Pharmaceuticals) 5/325, 10/650.

   Sometimes Dr. Suzuki might prescribe extended-release oxycodone (Oxycontin, Purdue Pharma) if the patient has chronic pain and has been on opioid medications for a long time. If that is not enough, he will not hesitate to send patients to the pain management clinic as they may benefit from a transdermal pain patch or spinal injections of anesthetic/steroid medication.

Q: What drugs do you use to treat neuropathic pain?

A: Although there are several drugs that physicians may utilize for painful diabetic neuropathy (PDN), Dr. Rogers notes only two drugs have a FDA indication for this type of pain. These drugs are duloxetine (Cymbalta, Eli Lilly) and pregabalin (Lyrica, Pfizer). Dr. Suzuki mostly prescribes pregabalin 50 mg (starting with qhs and titrating up to TID) and duloxetine 30 mg (starting with QD for one week and then titrating up to 60 mg QD). He may add acetaminophen and opioid pain medications if the pain is severe but Dr. Suzuki says opioids should be a last resort.

   Dr. Rogers says other drugs that are commonly used without specific PDN indications are amitriptyline (Elavil, AstraZeneca), gabapentin (Neurontin, Pfizer), tramadol (Ultram, Ortho-McNeil) and oxycodone.

   Dr. Rogers notes that reviews of drug efficacies using the number needed to treat (NNT) can provide some guidance. He emphasizes caution when it comes to ensuring proper dosing. Dr. Rogers points out that dosing used in clinical trials is often higher than the dosing noted in the indications for the given drug, and dosing can vary depending upon what you are treating.

   For example, Dr. Rogers says the dosing for gabapentin in the Physicians Desk Reference is 100 to 300 mg/day but he cautions that this dosing is for the drug’s approved epilepsy indication, not painful neuropathy. Research has shown that one must prescribe gabapentin in excess of 1,800 mg/day (divided TID) in order for the medication to be effective for neuropathic pain, according to Dr. Rogers.1 Dr. Suzuki has found gabapentin frustrating given its gradual upward tapering and pain relief that can be hit or miss.

   Dr. Suzuki formerly prescribed tricyclic antidepressants for neuropathy but says the side effects can be harsh and intolerable for many patients. When it comes to painful diabetic neuropathy, Dr. Satterfield notes she has had less than 30 percent of patients achieving pain relief with amitriptyline. When she has combined this with acetaminophen, patients had 60 percent achieving pain relief at night. Dr. Satterfield notes that some physicians add diphenhydramine (Benadryl) to help patients with DPN get through the night.

   Although advances in medicine have gone beyond this “neuropathy pain cocktail” combination, Dr. Satterfield says this can still be “a good option” for patients who do not have good insurance and cannot afford the newer generation drugs.

   Dr. Satterfield reminds DPMs of the transient nature of diabetic neuropathy. She notes that it can be painful at times and patients can have no sensation from this at other times.

   “It is those painful episodes we have to treat,” maintains Dr. Satterfield.

Q: Do you have a supplement of choice for neuropathic pain?

A: Dr. Suzuki has found some success treating neuropathic pain adjunctively with Metanx (Pamlab), a supplement comprised of folic acid and vitamin B complex, which reverses the endothelial dysfunction and increases the nitric oxide release. He cites a recent study indicating increased cancer incidence and mortality after treatment with folic acid and vitamin B12.2 Although the study may not be completely applicable with Metanx, Dr. Suzuki says it is something to consider.

   Dr. Suzuki notes clinical evidence that some antioxidant supplements, such as alpha lipoic acid, may slow down the progression of diabetic neuropathy. The SYDNEY 2 trial showed that 600 mg of alpha-lipoic acid once a day PO improved neuropathic symptoms and deficits in patients with diabetic neuropathy as early as four weeks of treatment.3 The NATHAN 1 trial also showed that alpha-lipoic acid was well-tolerated and improves some neuropathic deficits and symptoms in mild to moderate neuropathy.4

   Dr. Satterfield has used “the whole gamut of supplements” for painful diabetic neuropathy. While she believes some supplements have a positive effect, she calls for more randomized, controlled studies to prove their efficacy. To date, Dr. Rogers says no randomized, controlled trial has shown dietary supplements to be effective for neuropathic pain.

   “I refuse to use a dietary supplement for neuropathic pain and consider it cruel if it were the sole treatment,” says Dr. Rogers.

   Furthermore, Dr. Rogers notes the etiology of diabetic neuropathy is not a vitamin deficiency but likely a hypoxic nerve injury from microvascular damage. He compares diabetic neuropathic pain to the pain of the foot falling asleep and waking up.

   “Now imagine that the only treatment your doctor offered you for this pain was a vitamin. How satisfied would you be with this treatment?” he asks. “There is also a lack of sound evidence to use supplements for non-painful sensory neuropathy but it probably does no harm to use them adjunctively.”

   Dr. Rogers is an Associate Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a Fellow of the American College of Foot and Ankle Orthopedics and Medicine.

   Dr. Satterfield is an Adjunct Associate Professor at the Western University College of Podiatric Medicine. She is a Fellow and President-Elect of the American College of Foot and Ankle Orthopedics and Medicine.

   Dr. Suzuki is the Medical Director of Tower Wound Care Center at the Cedars-Sinai Medical Towers. He is also on the medical staff of the Cedars-Sinai Medical Center in Los Angeles and is a Visiting Professor at the Tokyo Medical and Dental University in Tokyo, Japan.

References:

1. Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther 2003 Jan;25(1):81-104. 2. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009 Nov 18;302(19):2119-26. 3. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 2006; 29(11):2365-2370. 4. Ziegler D, Low PA, Boulton AJ, et al. Effect of 4-year antioxidant treatment with α-lipoic acid in diabetic polyneuropathy: the NATHAN 1 Trial. American Diabetes Association meeting Poster presentation, 2007. 5. Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. 6. MacKay D, Miller AL. Nutritional support for wound healing. Altern Med Rev. 2003 Nov;8(4):359-77. 7. Magalhães MS, Fechine FV, Macedo RN, et al. Effect of a combination of medium chain triglycerides, linoleic acid, soy lecithin and vitamins A and E on wound healing in rats. Acta Cir Bras. 2008 May-Jun;23(3):262-9. 8. Alleva R, Nasole E, Di Donato F, et al. Alpha-lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy. Biochem Biophys Res Commun. 2005 Jul 29;333(2):404-10. 9. Robbins WR, Staats PS, Levine J, et al. Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg. 1998 Mar;86(3):579-83. 10. Williams JZ, et al. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg 2002; 236(3):369-375.