Chronic pain serves an indicator of wound pathology and may be a barrier to timely and aggressive care of chronic wounds. Pain management, as in all care settings, presents a unique set of challenges for the clinician in the outpatient clinic. Pain is subjective and complex, and multiple factors contribute to a patient’s perception of pain, including one’s gender,1 genetics, comorbid anxiety and/or depression, and social and environmental context. A patient’s expectations and mood can also directly impact perception of pain. Thus, no two individuals will have the exact same perception to the same pain stimulus.2 The need for pain management in the wound clinic may be due to acute pain or chronic pain. Patients living with chronic wounds may develop chronic pain due to the wound conditions themselves and/or due to comorbid conditions, such as diabetic peripheral neuropathy. Patients may also experience acute pain (sometimes overlaid on chronic pain) due to debridement and other wound-management procedures. When faced with acute on chronic pain, a careful assessment of the patient’s home medication regimen is important, particularly if an assessment is made that results in the patient requiring opioids for acute pain during procedures. Consideration for pain management should involve a strategic, holistic approach utilizing various modalities, including opioids, adjuvants such as NSAIDs, antiepileptics, topical analgesics, and nonpharmacologic treatment modalities. Careful pain assessment is key to uncovering which treatment modalities will be most therapeutic for a patient’s pain. When considering a patient for opioid therapy, a risk assessment for the risks of misuse, abuse, and diversion should be conducted prior to prescribing, per numerous published guidelines.3-5 The discussion on conducting risk assessment is outside the scope of this article, but numerous professional guidelines and resources exist on this specific subject.
To illustrate these scenarios, this article will offer a series of five case studies that portray different aspects of pain-related problems commonly encountered in the wound clinic.
MANAGEMENT OF PAIN DIRECTLY DERIVED FROM WOUNDS
“DB,” a 69-year-old retired Air Force officer, developed painful ulceration of both lateral low legs over a period of several months, which she attributed to a reaction to a bug bite. She states that the wounds developed spontaneously, gradually increased in size, and were constantly aching. On examination, she presented as a slender, fit, woman, who appeared younger than her stated age. The wounds on her lateral calves were quite extensive, measuring on the left approximately 18 cm x 8 cm by a maximum depth of 0.4 cm, and on the right 14 cm x 7 cm with a maximum depth of 0.4 cm. Both wounds were filled with slough, black necrotic tissue, and some exposed deeper structures without granulation. The wound margins were purpuric, appeared inflamed, and surrounded by erythema, as well as what appeared to be a reticular pattern on the skin. There was no significant peripheral edema on either of the low legs. She did, however, exhibit extensive venous varicosities in the low legs. Noninvasive vascular testing modalities, including ankle-brachial index (ABI) and transcutaneous oximetry, were normal. Cultures performed at the time of initial evaluation showed no growth.
Initially, she underwent sequential debridements under topical anesthesia, over three weeks, as well as single-layer compression bandaging. The presumptive diagnosis was “venous leg ulcers, in spite of minimal edema.” Paradoxically, the wounds began to grow larger, deeper, and with increasing periwound inflammatory response. The patient also continued to experience significant pain, both with attempts at debridement and on an ongoing basis, in spite of leg elevation and compression. Ultimately, a biopsy was performed, revealing only chronic inflammation. Laboratory studies for autoimmune disease revealed elevated antinuclear antibodies, although titers were normal for rheumatoid arthritis (RA) factor and lupus. By exclusion, the presence of pyoderma gangrenosum was determined, although the patient was among the considerable proportion of those who had no other definable autoimmune disease.6
No further procedures or debridement were performed, in hopes of avoiding additional pathergy. Referral was made to a rheumatologist, who started high doses of prednisone, which failed to alleviate the pain or reduce the dimensions and severity of the ulceration, and unfortunately led to hospitalization for a bleeding gastric ulcer. Even after some positive response to newer biologic agents, healing was not achieved. The patient had been undergoing monthly treatment in the wound center for the eight years, and at times requested prescriptions for opioids. Most recently, she was started on tofacitinib (Xeljanz®), an immune system modulator indicated for treatment of RA not responsive to disease-modifying antirheumatic drugs. After starting this treatment, the ulcers appeared to be markedly less inflamed and progressing towards closure. This overall improvement in dimension and physical appearance seemed to result in a marked decrease in the consumption of opioids.
• Avoidance of procedures/instrumentation:
Although weekly debridement has been shown to enhance healing rates7, clearly there are conditions that obviate the use of surgical instruments to aggressively remove necrotic tissue from the wound bed. Autoimmune ulceration, including p. gangrenosum and vasculitis, radiation soft tissue necrosis, and arterial ulcers associated with critical limb ischemia (CLI), should not be treated with extensive debridement.8,9 Pathergy and exacerbation of pain often ensue.10
• Analgesia choices:
In the current environment, wound care clinicians may be hesitant and fearful of prescribing opioids for pain control. Patients should always be carefully evaluated for appropriateness of prescribing any medication, and opioids are no exception. Nevertheless, there are cases that warrant oral opioids. Initially, NSAIDs may be used, however, patients may be at risk for side effects and drug interactions, including gastrointestinal effects and interaction with anticoagulants. In the case of this patient, with a history of bleeding gastric ulcer NSAIDs would be contraindicated. If opioids are prescribed, individualization of therapy may help to target the agent that would be most effective in alleviating chronic wound pain, balanced with individual risk.
• Pharmacogenetic testing as an adjunct to optimal analgesic selection:
Pharmacogenetic testing may be a useful adjunct to optimal analgesic selection and is now commercially available.11 Many commonly prescribed opioids are metabolized via the cytochrome P450 (CYP) 2D6 pathway, including codeine, hydrocodone, oxycodone, and tramadol. Patients who have variation in the CYP2D6 gene may not have the desired analgesic effect to these medications, or may experience toxicity leading to respiratory depression or other adverse events. Guidelines are available for the use of CYP2D6 genetic testing results in prescribing opioids.12 Moreover, variation in other genes has also been associated with response to opioids, and genetic variation has been shown to impact response to other analgesics, such as celecoxib.13
• Treatment of the underlying condition to alleviate pain:
In this case, treatment of the autoimmune process provided progression toward healing of long-standing wounds, and consequently, relief of chronic pain. Although the patient has been taking opioids most days for at least 10 years, her need for opioids to manage pain decreased in parallel to the improvement in her wounds. The wound clinician may be challenged to distinguish the type of pain (painful neuropathy versus pain from wounds versus ischemic pain). The ultimate source of reported pain dictates the best interventions to provide relief. Neuropathic pain may require antiepileptics, such as gabapentin or pregabalin. Ischemic pain may be intractable to systemic analgesics and may need to be relieved with urgent revascularization.
• Integrative medicine approaches — acupuncture:
Alternatives to analgesia with medications include nonpharmacologic interventions. Acupuncture, for example, has been documented to be effective in some patients for management of direct pain in a wound or for neuropathic pain.14,15 Whose job is it (primary care versus wound care versus pain management)? Some wound clinicians are comfortable with prescribing analgesics, especially if the pain appears to emanate directly from the wound. Nevertheless, to maintain consistency, to deal with non-wound-related pain issues, and to include the primary provider as part of the healthcare team, it may be wise to relegate long-term prescribing to the patient’s “medical home.” For those patients who seem to have intractable issues or who solicit opioids from multiple providers, it may be best to refer to a pain specialist.
STRATEGIES FOR MANAGEMENT OF ACUTE PROCEDURAL PAIN
“TP” is a 26-year-old old, unemployed construction worker who sustained a comminuted fracture of the right calcaneus during a crash on his dirt bike. He was not adherent to leg elevation and developed extensive hemorrhagic fracture blisters, which became infected, requiring hospitalization for several weeks. He was referred to the wound clinic for debridement and long-term management of the open wounds on his lateral and medial proximal foot and ankle. Assessment revealed an anxious young man. The wounds on the right foot and ankle were about 20 cm2 combined, at minimum full-thickness, and with a minimum depth of 2 cm. Physical examination revealed minimal granulation and extensive necrotic tissue, including both eschar and slough, obscuring the base of the ulcers. There was not significant local edema.
After vascular evaluation, the patient consented to sharp debridement, and topical 4% lidocaine-soaked 4x4s were layered onto the wound bed. After 15 minutes, the gauze was removed and the provider initiated debridement, utilizing a 4-mm bone curette. After the first pass of the instrument, the patient began crying in pain and withdrew his foot from the procedural field due to the pain being “unbearable” and refusing further attempts at debridement without additional pain control. When the staff suggested local anesthetic injection, he also refused, citing a fear of needles (this despite his extensive tattoos, which extend from his lower legs to his feet). After coaxing, he agreed to an attempt at debridement utilizing a 10-blade scalpel and forceps, with supplementation of topical anesthesia (4% lidocaine liquid on gauze). He was able to tolerate removal of the preponderance of the necrotic tissue in the wound.
• Choice of analgesia/anesthesia:
Topical/Injectable/Inhalation/psycho- prophylaxis: Discussion: The patient represents a relatively more difficult individual regarding pain management who could present to an outpatient center. Although topical anesthetics (with lidocaine most commonly used) are the mainstay of pain management during most outpatient bedside procedures, at times it proves inadequate relief. This can be the result of poor penetration through necrotic tissue present in the wound bed, as well as patient factors including psychological and genomic differences in perception of pain, hyperalgesia due to chronic reinjury, or even genetic predisposition for attenuated response to lidocaine and related anesthetics.16 Although infiltration of local anesthetics will more than likely overcome problems with penetration, some patients, as in this case, are severely phobic regarding injection. In some centers, mixed gas nitrous oxide and oxygen-delivery systems are available. Although the patient remains conscious, this system can provide up to five minutes of mild to moderate analgesia, as well as anxiolytic effects after few inhalations. Although not commonplace, there are outpatient centers where extensive debridements are performed utilizing intravenous propofol under the supervision of an anesthesiologist or nurse anesthetist. Anesthetic and analgesic choices notwithstanding, setting expectations by demystifying the process through preprocedural discussion with the patient in order to help alleviate anxiety is advised.
• Choice of instrument to minimize pain: Curette, scalpel, scissors, or “tissue nippers.”
Wound clinicians will be well served by being flexible in their choice of surgical instruments to perform debridement and other potentially painful procedures. As illustrated previously, sometimes the use of a scalpel, accompanied by forceps with teeth to lift nonviable tissue, is preferable to a curette, because a scalpel can be wielded more delicately and selectively. Curettes don’t have a particularly sharp edge and require significant pressure on the wound bed to break up dense fibrosis, slough, or necrosis. The downside of debridement with a scalpel versus a curette is that it may take longer to complete the procedure. Alternatives to the use of a scalpel, scissors, and forceps, or tissue nippers (resembling miniature nail clippers), can be effective in trimming hyperkeratotic, fibrotic, or rolled wound margins, both more effectively and with far less discomfort than would be affected by the use of a curette.
• Clinic versus operating room: Where to perform the procedure?
In extreme cases of hyperalgesia or inability to tolerate bedside procedure, debridement might be required at a surgery center or in the hospital’s surgical suite, under minimum-conscious sedation or general anesthesia. Given that this greatly increases the cost of care, it normally cannot be done weekly, as is the standard in the outpatient clinic, and puts the patient at significantly increased risk. This is to be avoided unless there is no other viable option.
NONPHARMACOLOGIC MANAGEMENT OF PAINFUL LEG WOUNDS & SEVERE EDEMA
“MJ” is a 48-year-old hairstylist who presented to the wound center with extensive full-thickness leg ulceration on the left lateral calf. Her wound is associated with significant pain, especially after being on foot for several hours, as well as severe leg swelling occurring daily while at work. The ulcer has persisted for several months and she has been self-treating with topical dry dressings. Physical examination reveals a slightly obese, tall woman. The wound on her left lateral calf measures approximately 35 cm² with a depth of about 3 cm. Copious fibrin is present in the wound bed as well as a minimal degree of granulation. There is copious serous drainage. Wound margins are irregular, thickened, and somewhat rolled. There are hyperpigmented areas of somewhat-fibrotic skin surrounding the wound with 3+ pitting edema present on both legs. Noninvasive vascular assessment reveals an ABI of 1.1 in both legs. After topical application of 4% lidocaine liquid on gauze pads, debridement is attempted through the use of forceps and scalpel. In spite of adequate duration to allow penetration of the topical anesthetic, the patient was unable to tolerate the procedure. The clinician decided to defer debridement until a subsequent visit. Antimicrobial dressings were placed on the wound bed, zinc oxide-based barrier cream was placed on the periwound area, and multilayer compression bandaging was applied. The patient noted significant relief of discomfort after application of the multilayer compression bandage. Two days after the initial visit, she returned for reapplication of the multilayer compression bandage and reported a significant decrease in overall pain (especially when on foot) and the edema was well-controlled. Debridement was reattempted successfully, and the patient noted only minimal discomfort during the procedure.
• Edema = pain:
This patient exemplifies a significant issue encountered in wound clinics: Edema causes and contributes to pain. From a purely mechanistic viewpoint, it is logical to consider that when tissue is distended by interstitial fluid structures within that tissue will undergo traction or stretch. The neurons that generate pain are delicate structures, which when subjected to stretch are more likely to “fire.” An apt analogy is that a taut rubber band will vibrate, while a lax or flaccid one will not. The clinician has the luxury of knowing there are very few wound emergencies, and there is no rush to immediately perform a debridement when a noninfected wound is surrounded by tense edematous tissue. It is perfectly reasonable to defer a potentially painful procedure to a time when the patient will be more comfortable. In the case of this patient, delaying the instrumentation until the second visit yielded a satisfactory outcome.
• Compression as pain control:
Compression therapy to reduce overall pain response in patients living with edema is often unrecognized. A far greater proportion of patients will report reduction or absence of pain after undergoing compression therapy, especially with multilayer bandaging.17,18 There may be some patients who experience confinement anxiety, are concerned with daily bathing, or have uncontrolled itching with long-term compression, however, the majority seems to tolerate the treatment without significant difficulty. A common practice, without a basis in evidence, among clinicians is to start patients on single-layer compression and to eventually escalate to multilayer bandaging to see if compression is tolerated. The inherent flaws in this approach are that edema control is less effective with single-layer bandaging due to patient adherence, as well as application competency issues, and that the extra padding in multilayer compression provides additional comfort over single-layer bandaging. Assuming that a patient has adequate macro-arterial circulation in the affected extremity, the first line of compression treatment should involve multilayer bandages.19-21 Those fastidious patients who balk at the prospect of multiday compression due to their desire to shower daily can be directed to purchase a low leg cast protector, which is available in most pharmacies. Single-layer compression should be used at the lowest level (20-30 mmHg) and should be limited to patients living with potential CLI or those who simply cannot tolerate the confinement of multiday bandaging.22,23
• Leg elevation as pain control:
Those patients living with leg ulcers, edema, and pain who are unable to tolerate any type of compression bandaging and do not have resting arterial pain can be managed as much as possible through leg elevation. Elevation of the lower leg above the level of the heart is the only effective intervention. Patients must be counseled that sitting up with their leg extended and parallel to the floor does not constitute effective edema control.
• Management of ischemic pain:
As briefly discussed previously, ongoing or resting pain in a patient with suspected or documented arterial disease is an urgent medical issue. Persistent aching pain associated with low leg or foot ulceration, with or without edema, in the setting of vascular compromise is analogous to an acute coronary syndrome. This is a potentially limb-threatening condition and should be approached as such. Immediate referral either directly for hospital admission or to an interventional vascular specialist is the critical action that should be undertaken. Resolution of the pain might only be achieved with revascularization.
Case Study No. 4: PAIN MANAGEMENT AS A SOURCE OF CHRONIC WOUNDS
“LM” is a 70-year-old female living with severe bronchiectasis, severe migraines, and intractable nausea as a side effect of long-term opioid therapy and frequent courses of antibiotics. She was largely bedbound, homebound, and cared for by her adult children. Her daughter is trained in intramuscular injection, and to avoid frequent and exhausting trips to the emergency department (ED) or the primary physician’s office, the patient received daily (or more frequent) shots of hydromorphone and promethazine. As the bronchiectasis progressed, the patient became cachectic and had little muscle mass or subcutaneous fat on the buttocks, her preferred location of injection. Also, after nearly 10 years of intramuscular injections, almost all of the surface area of the posterior pelvis had become scarred and fibrotic, rendering intramuscular infiltration problematic. She presented to the wound clinic with multiple nonhealing, full-thickness wounds to both buttocks and upper thighs. On examination, she was revealed to be emaciated with extensive interconnected and undermined fibrotic ulcers. There was almost no granulation in these wounds, and probing revealed fascia or ligament at the base. All ulcers had rolled margins and almost appeared to be narrow tracts without roofs. There was minimal serosanguineous drainage, no pus, and no redness indicating infection. Ultimately, it was obvious that these wounds were sterile abscesses, most likely secondary to repeated infiltration with promethazine. Cultures for pathogens were essentially unremarkable, and biopsy of the walls of one of the ulcers revealed chronic inflammation only. Debridement of these ulcers was largely avoided because the patient had such severe protein calorie malnutrition that healing was unlikely. Additionally, episodes of chronic pain and nausea were recurrent and ongoing, and both the patient and her daughter were unwilling to relinquish the intramuscular injections. The patient agreed to be admitted to a long-term acute care hospital for failure to thrive, where she had placement of a percutaneous endoscopic gastrostomy tube and an implantable port in her chest wall for intravenous injection. After some improvement in nutritional status, as indicated by weight gain and rising prealbumin levels, she also underwent excision of the tracts with flap closure, leading to successful healing.
• Management of wounds caused by injection:
Sterile abscesses, as well as infected abscesses caused by injection, are frequently encountered in the wound clinic. In most cases, management is standard, including debridement and topical absorbent antimicrobial dressings. This was an extreme case. The patient’s severe muscle-wasting and loss of subcutaneous fat, as well as repeated injury through daily injection of irritant medications, rendered her very difficult to manage. Her placement into an acute care hospital was the definitive action in bringing about healing.
• How to prevent recurrence:
Prevention of recurrence of sterile abscesses may involve cessation of injection. Unfortunately, the patient could not discontinue the pain- and nausea-management regimen. Placement of a permanent injection port would appear to be an aggressive solution to this case. Clearly, an intravenous injection port is fraught with potential complications, including local infection or sepsis. Placement of the port is not to be undertaken lightly. Fortunately, the patient’s daughter was medically competent to manage the port and the administration of medications.
• Referral for pain management:
Most patients with injection ulcers from analgesics and/or antiemetics do not require the intervention applied to this patient. Wound care in such cases is normally standard, however, provision of alternative analgesia and nausea abatement are beyond the scope of the wound clinic. Outpatient referral to a pain-management specialist is indicated in these cases.
Case Study No. 5: WOUND PAIN MANAGEMENT FOR PALLIATIVE CARE AT END OF LIFE
“LD,” a 63-year-old woman living with fungating breast cancer, was referred to the wound clinic for management of drainage, odor, and bleeding to the left breast. She has chosen not to undergo surgery, chemotherapy, or radiation and has pursued a palliative course of care. She has made several ED visits in the last several months, with episodes of moderate hemorrhage that would not stop with simple sustained pressure at home. Her main complaints are concerns regarding bleeding and the ongoing aching pain related to the progressive distension of surrounding tissues.
Physical examination revealed a healthy-looking female (aside from the left breast being almost twice the size of the right, with tissue obviously replaced by tumor mass). The overlying skin was taut and erythematous, and there was ulceration and a nodular mass protruding from the medial base of the breast adjacent to the sternum. This mass measured about 6 cm x 8 cm and was necrotic, malodorous, and draining serosanguinous fluid. The tissue was friable and would bleed from light contact with gauze or even paper rulers. Based on the patient’s desire for palliative care only, the clinician formulated a treatment plan comprised of silver alginate to reduce odor, absorb drainage, and control hemorrhage. To prevent inevitable adherence of the absorbent antimicrobial dressing, a contact layer of oil emulsion gauze was to be applied prior to the alginate. The patient was counselled on bleeding management and when to seek urgent or emergent medical intervention. Since debridement was to be avoided, weekly visits were not indicated, so follow up was scheduled to occur every two weeks. Prior to being discharged, the patient said she was only taking acetaminophen currently for pain management. Her primary care physician was contacted, and he requested that, if indicated, the wound clinician prescribe opioids and manage opioid therapy.
• Avoidance of procedures:
The patient had a malignancy and a high risk of life-threatening hemorrhage. It was obvious that the wound clinician should not perform debridement. There are other patients for whom debridement might not be high risk but would be of little benefit given that they are either close to the end of life or have elected a palliative course of care (with goals of care being wound management versus healing). The wound provider can exercise judgement in deciding not to perform potentially painful procedures with little potential for changing outcomes.
• Choice of dressings:
The need for control of odor, bleeding, and drainage indicated the use of a topical absorbent antimicrobial dressings that had hemostatic capacity for this patient.
The treatment required further customization to avoid adherence of the alginate, since its removal at dressing change could put traction on friable vascularized tissue and trigger hemorrhage. For other palliative patients, the goal should be to avoid dressings that require frequent, painful changes. Products that can be applied for several days are preferred over daily dressings. Customization of treatment protocols is essential in end-of-life wound management.
There is no single solution to the varied issues of pain management in the outpatient wound clinic. The healthcare team must individualize pain-control modalities to the patient’s unique physical presentation, psychological perception of pain, and underlying etiology. Additionally, the subset of patients for whom the goal is palliation can present unique cases where the goals of care are maximization of comfort as opposed to “healing.” n
Roger B. Schechter is medical director for wound management at Palomar Health, North San Diego County, CA, and is a consultant for the DxWound molecular diagnostic test offered by Millennium Health LLC and its genetics brand CogenDx.
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