Mitigating the Opioid Crisis for Wound Care Providers Using Opioid Stewardship

Opioids are an effective form of analgesia for pain treatment during wound treatment. Overprescribing of opioid agents has become detrimental to the public health of the United States. One of the most difficult challenges for any wound care prescriber is to balance the potential benefits versus the potential risks of opioid prescribing. Addressing the opioid crisis requires an interprofessional team approach. The utilization of an opioid stewardship program provides the necessary framework to identify gaps in the quality and development in the implementation of a change of long-standing opioid culture and practice. These programs address opioid prescribing, treatment for opioid use disorder, educational initiatives, and the use of information technology. A few acronyms have been created to assist providers to guide them when prescribing opioids. The purpose of this article is to explore the central theme of responsible opioid pain management. It will introduce, define, and defend with clinical-based evidence a proposed acronym, “MORPHINE,” to assist and help shape prescription opioid strategies used for wound care treatment. Implications for practicing wound care specialists need to acknowledge the potential harm that prescribing opioids may cause to their patients.

Bechert and Abraham¹ reported that pain is often an overlooked factor in wound care and wound healing that affects wound care practice, and the nature of pain a patient experiences is directly related to the type of wound sustained. They,¹ along with others,² assert that pain is multidimensional and involves both physiological and psychological components. At the physiological level, wound pain develops from tissue damage or dysfunction of the nervous system. Chronic wound pain may be born of both nociceptive and neuropathic elements.³ Wound pain is an individualized experience and differs from patient to patient based on their personal, familial, and cultural backgrounds, thereby leading to variations in a patient’s experience and expression of pain. The wound care specialist may heed that pain is whatever the patient reports, and it needs to be addressed accordingly.

The World Union of Wound Healing Society’s consensus document³ categorizes wound pain as follows: (1) background pain or basal or baseline pain¹ is the continuous or intermittent pain felt by the patient even at rest, which includes pain associated with an infection; (2) incident pain or breakthrough pain¹ is described as pain that occurs during the patient’s day-to-day activities, including during patient mobilization and even when the patient is coughing; (3) procedural pain is described as pain that results from routine procedures, such as dressing or ostomy pouch changes or wound cleaning; and (4) operative pain is described as the pain associated with significant wound interventions, including wound debridement and wound biopsy. Operative pain may be severe enough to require anesthesia.³

The National Institutes of Health Interagency Pain Research Coordinating Committee has asserted that “when opioids are used as prescribed and appropriately monitored, they can be safe and effective for acute, postoperative, and procedural pain, as well [as] for patients near the end of life who desire more pain relief.”⁴ Opioids are an effective form of analgesia for pain treatment. Overprescribing of opioids due to the prescriber’s lack of knowledge about different opioid molecules and available technologies has become rampant in the United States. One of the most difficult challenges for medical providers is balancing the potential benefits and risks of opioid prescribing. An interprofessional team approach is required to curtail the opioid crisis. The adoption of an opioid stewardship program (OSP) provides the necessary framework to identify gaps in quality, development, and implementation to alter the long-standing opioid culture and practice.^5-7 Sandbrink and Uppal⁵ assert in their commentary the need for an opioid stewardship model as presented and detailed by Weiner et al.⁷  First, the program should encourage the use of non-opioids as first-line treatment programs.⁶ Subsequently, these programs should provide pathways for safer opioid use when opioids are indicated.⁶  Lastly, these programs should identify patients with opioid use disorders and engage them in treatment.⁶

These programs address opioid prescriptions, treatment for opioid use disorder, educational initiatives, and the use of information technology. The wound care specialist can appreciate the concept of opioid stewardship, the origins and principles of which are in currently established antimicrobial stewardship accepted across practices. The following 7 fundamental actions support the practice of opioid stewardship within the interprofessional health care arena: (1) promotion by leadership to commit to change in the existing culture; (2) implementing organizational policies; (3) advancement of clinical knowledge, expertise, and practice; (4) enhancement of patient and family caregiver education; (5) tracking, monitoring, and reporting performance data; (6) establishment of accountability; and (7) supporting a network through community collaboration.⁸ 

The clinical literature reports that link legitimate opioid prescriptions with opioid misuse, abuse, and opioid diversion are available. Any surgical intervention procedure represents a potential gateway to opioid dependence, and clinicians treating lower extremity wounds must recognize and develop methods as they embrace their role as stewards of safe opioid use. Given that opioid overdoses have increased over the last decade, it is imperative that physicians who specialize in wound care assume ownership of their role in curtailing opioid misuse and abuse.

A few acronyms have been created to assist providers in guiding them when prescribing opioids.^9,10 The central theme of this review is responsible opioid pain management. It will introduce and define the acronym “MORPHINE” to assist during opioid prescribing to treat pain. Each letter of the acronym MORPHINE stands for an essential principle of opioid stewardship. Clinical-based evidence will be presented to defend the use of the MORPHINE acronym by providing an argument highlighting current ethical prescribing standards and legal regulations in the context of opioid stewardship principles aimed at alleviating the widespread opioid crisis that wound care providers face daily.

“M” stands for multimodal analgesic strategies. A multimodal analgesic approach is likely to produce superior analgesia over the use of an opioid-based approach because multimodal analgesic agents target a variety of pain pathways.^5-7 Published clinical-based evidence has described the effects of employing local anesthetic products to mitigate postoperative pain and reduce the need for opioid analgesics. Kohring and Orgain¹¹ declared that local anesthesia techniques provide excellent pain relief without adverse events. Multimodal analgesia for pain management is now widely applied to reduce opioids and opioid-related side effects. 

The foundation of a wound care clinician belief system is that wound healing occurs in distinct and overlapping phases, which include hemostasis, inflammation, proliferation, and maturation. Wang et al¹² examined the contribution of mu-opioid receptors in mediating the healing of full-thickness ischemic wounds using mu-opioid, delta-opioid, and kappa-opioid receptor knockout mice. Endorphins and analgesic opioids, including morphine, have been demonstrated to stimulate endothelial proliferation, survival, and angiogenesis in wounds and tumors via mu-opioid receptors mediating phospho-mitogen-activated protein kinase/extracellular signal-regulated kinase signaling.^13-16 Wang et al¹² found the expression of mu-opioid receptors is significantly higher in wounds compared with intact skin and co-localized with vasculature and the epidermal layer. Keratinocytes play a critical role in skin homeostasis and epithelialization phases via delta-opioid receptors.¹² Their conclusions suggest that opioids offer a unique advantage in treating wounds because of their ability to concurrently stimulate revascularization and reduce neuroinflammation.¹²

The analgesic ladder proposed by the World Health Organization¹⁷ (WHO) is a useful reference in applying and accentuating an opioid stewardship approach when treating acute and chronic pain, starting with non-steroidal anti-inflammatory agents and ending with opioid medication. The use of a non-opioid analgesic with or without an analgesic adjunctive agent is the first step or rung in the WHO ladder.^1,17 Many non-opioid multimodal agents are inexpensive and benefit patients by resulting in a lower consumption of opioids. Examples of drugs with differing mechanisms of actions that target pain pathways in additive and/or synergistic effects include acetaminophen, alpha-2 agonists, dexamethasone, duloxetine, gabapentinoids, N-methyl-D-aspartate receptor antagonist, non-steroidal anti-inflammatory agents, selective cyclooxygenase inhibitors, and topically applied medications.^11,18–21 

Topical pain relief medication can be prescription-based, over-the-counter, or homemade. Topical pain relievers should always be tested on a small area of the skin since some can cause irritation.²¹ Transdermal and topical routes of opioid administration also are associated with a lower risk of addiction compared with oral and parenteral routes of opioid analgesics administration.²² Pain resulting from certain conditions such as osteoarthritis, peripheral neuropathy, and fibromyalgia can be reduced with capsaicin,²¹ which is available in both cream and gel forms. Capsaicin is prepared from chili peppers and delivers a hot sensation to the region where applied. After exposure to capsaicin, nociceptors in the skin become less sensitive to different stimuli; therefore, the late action of capsaicin is depicted as anesthesia.²² Lidocaine is a local anesthetic cream that causes temporary numbness, thereby minimizing pain in the treated area.²¹ A secondary mechanism of lidocaine is associated with an inhibition of the release of nociception process mediators by keratinocytes.²² Topical lidocaine is generally used for arthritis and other musculoskeletal conditions. Trolamine salicylate cream is often recommended for arthritis pain.²¹ Trolamine salicylate is chemically similar to aspirin and provides a slight anti-inflammatory effect. Ingredients such as menthol, wintergreen, and eucalyptus in counterirritant topical agents create a hot or cold feeling.²¹ Counterirritant topical agents are often used for treating sore muscles; they can typically be used with other forms of pain relief. Lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream (Astra Pharmaceutical Production), and creams containing antidepressants (eg, doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels.²² Non-steroidal anti-inflammatory drugs (NSAIDs) performing the basic action of blocking prostaglandin formation are an important component in the treatment of this type of pain.²² Topically administered NSAIDs are normally used for a period of 1 to 2 weeks and are effective in the following types of pain: musculoskeletal, mainly suffered after injuries; soft tissue pain; and rheumatic diseases.²²

Shanmugam et al,²³ building on previously published literature, emphasized the importance of using an opioid stewardship approach when treating chronic wounds and thereby adding to the body of knowledge, which proposes that the use of opioids may attenuate the healing of chronic wounds. These investigators have suggested that opioid use may negatively impact wound healing by reducing immune activation, impacting tissue oxygenation and angiogenesis,^24,25 and altering myofibroblast recruitment as well as impacting keratinocyte cytokine production and endothelial proliferation.^25,26 The investigation by Shanmugam et al²³ used data collected through the Wound Etiology and Healing (WE-HEAL) study to investigate the relationship between patient-reported pain, opioid exposure, and wound outcome in the clinical care of a longitudinal cohort of patients with chronic wounds. Three major conclusions presented at the end of their investigation²³ are summarized as follows: (1) patients who never received opioids in the WE-HEAL study healed faster than those who received opioids; (2) opioid exposure was a strong predictor of wound size; and (3) patients who received opioids at doses above 10 mg per day had slower rates of healing than those with no exposure or dosages less than 10 mg per day.

“O” stands for the development of an opioid formulary. An opioid stewardship program can limit opioid initiation by creating prescribing guidelines.^6,7 Wound care specialists can create their own opioid formulary by rigorously and regularly administering 1 or 2 drugs for each clinical condition they commonly encounter. First, clinicians should use primary literature sources to include peer-reviewed, randomized, double-blinded clinical trials that compare medications. Subsequently, they may use secondary literature sources to include “Drug Facts and Comparisons” and “The Medical Letter on Drugs and Therapeutics” as well as review articles in peer-reviewed journals when comparing drug classes and to review recommendations centered around appropriate drug choice. Important considerations for objective opioid selection include drug efficiency, safety, patient acceptability, and cost. No single opioid analgesic may be perfect, and no single agent can treat all types of pain. Morphine-equivalent tables have been developed, and their purpose is to assist clinicians in determining equianalgesic doses of various opioid agents when changing or rotating opioid therapy. Opioid equianalgesic doses are presented in Table 1.

The underlying rationale for adopting combination strategies includes the availability of individual agents that induce analgesia through separate or overlapping mechanisms or that have separate adverse effects. The basic goal of a combination strategy is to amplify the desired effects while decreasing, or at least not equally increasing, the undesired effects in the individual agents. Second, when the pain is not controlled by initial medications, the addition of an opioid—for example, codeine—or the prescribing of tramadol or of an adjuvant agent is appropriate and within the principles of opioid stewardship.^1,17 The last step of the WHO approach is when the patient’s pain does not respond to the second-step medications and the clinician needs to discontinue the initial drug; in such cases, a more potent oral narcotic should be initiated.¹

“R” stands for recognizing and reducing the risks of opioid harm. Therapeutic success depends on proper candidate selection, assessment prior to the administration of opioid therapy, as well as close patient monitoring.^5-9 While substance abuse tools assess whether a patient was or is involved in alcohol or drug abuse, risk assessment tools measure additional factors involving a patient’s overall level of risk of developing abuse or addiction.^19,20 Beyond recording a comprehensive medical history via effective patient interviews, there are several risk assessment tools to help further evaluate the probability of the patient facing difficulty using opioid analgesics as prescribed. Screening for risk factors is ideally performed on the patient’s first visit or before prescribing opioids, and patients who have been consuming opioids for long periods of time should be routinely screened.¹³

“P” stands for pharmacokinetics and pharmacodynamics of opioids. Wound care providers must be aware of the possible deadly drug-drug interactions that result from dangerous combinations of opioid medications with over-the-counter products, herbal supplements, energy products, and prescription medications. At times, dangerous drug combinations are indeed prescribed for legitimate reasons, without prescribers realizing the possible dangerous effects. Furthermore, the disease states that the patients present during an encounter may affect or be affected by opioid treatments. Opioids are highly varied and generally thought to possess similar pharmacokinetic activity. Opioids are rapidly absorbed in the gut, feature a high rate of first-pass effects in the liver, conjugate in the liver, create metabolites, and vary in distribution based on their differing protein affinity; subsequently, they are excreted via bile to feces or via kidneys. Liver disease may make using acetaminophen challenging, while renal disease often prevents the use of NSAIDs.⁵ Therefore, the combination of clinical judgment with the interpretation of drug pharmacokinetics is often instrumental when prescribing medication. Guo et al²⁷ related that oral morphine has traditionally been widely used for treating patients with moderate or severe pain. Guo et al²⁷ identified no remarkable difference in analgesic efficacy or in the tolerability of oxycodone and morphine as the first-line therapy in patients experiencing moderate to severe cancer pain. In the context of opioid stewardship, clinical coping suggestions²⁸ pertaining to dosing opioids, taking into account patient demographics and disease states, are summarized and presented in Table 2.

“H” stands for help. The wound care specialist should seek a pain specialist when required. Pain management specialists can empower a patient’s ability to function and improve their quality of life.^6,7 Patients who have substance use disorders with medically legitimate pain sufficient to justify the administering of opioids must be closely monitored.⁶ Wound care clinicians can play an integral role in patient selection and referral for focused chronic pain management and provide ongoing collaborative care to include monitoring for efficacy and adverse events and facilitating communication with the treating specialist. Becker et al²⁹ reported the most important reasons to refer a patient to a specialist include: (1) misuse of medication, such as early and consistent refill requests or positive drugs screens; (2) excessive alcohol consumption; (3) no desire to try other pain treatments or medication options; (4) concurrent prescriptions for opioids and sedatives; (5) mental health symptoms; and (6) opioid use disorder being treated with methadone or buprenorphine/naloxone upon experiencing persistent, impairing pain. 

“I” stands for information technology. The ability to use information technology resources is critical to provide benchmarking of opioid use and the collection of metrics to create clinical decision support tools to build best practice models.⁶ The use of the electronic health record can prioritize non-opioid and non-pharmacologic pain management options and redirect clinicians who have historically been trained to practice using opioids as a first-line pain relief option.⁶ Opioid stewardship programs can leverage electronic health records to develop dashboards of opioid-use patterns by departments with the goal of reducing variability as a marker of quality care.⁶ Furthermore, these OSPs can provide an overview of regulatory changes and help evolve state laws that influence mandatory prescription drug monitoring program queries and consent for minors for opioid use and prompt the initiation of control substance agreements.⁶ Finally, the information technology arm of the OSP will assist with legal compliance at both the state and national levels.^5,6

“N” stands for the number of opioid doses. Ideally, OSPs can assist in ensuring that lower doses are prescribed to patients by using data collected by information technology tools.^6,7  Overton et al³⁰ found that procedure-specific prescribing recommendations may help provide guidance to clinicians who may currently overprescribe opioids following surgery. Ideally, opioid analgesics are prescribed by balancing the benefits and adverse effects. The appropriate combination of agents, including opioids and adjunctive medications, may be considered rational pharmacotherapy and provide a stable therapeutic platform to base treatment changes. Clinical literature findings suggest that 20 doses of an opioid agent may be sufficient to manage postoperative pain resulting from some orthopedic and lower extremity surgical interventions.^31-33 Finally, wound care physicians are encouraged to educate their patients about drug take-back programs in the event of their being prescribed excessive opioid doses.

“E” stands for education to multidisciplinary medical professionals, patients, and patient caregivers. It is paramount that an open dialog be fostered so that expectations of opioid therapy can be appreciated by all parties.^5-9 Furthermore, it is important for patients to understand that the goal of postoperative pain management, as asserted by Varley and Zuckerbraum,¹⁰ is not to be pain-free but to make the pain manageable in the context of a patient’s daily activities during their recovery. Opioid stewardship programs promote and enhance patient and family caregiver education and engagement. One tool that can assist in enhancing patient education is control substance agreements since such agreements promote communication between patients and providers, thereby creating an open and honest dialog revealing each individual’s expectations of a treatment plan. Multiple ways for reducing opioid abuse are available and strongly supported by health care providers, patients, policymakers, and other key stakeholders. These include educational endeavors centered on the risks of prescription opioids and other medications if not taken as prescribed as well as steps to ensure safe storage and disposal of expired, unwanted, or unused medications. Wound care clinicians should remind patients that medications should be stored out of the reach of children and in a safe place, preferably locked, to prevent other family members and visitors from taking them. A final educational initiative is to allow for empowering patients with information centered on the preferred options to dispose of unwanted or unused opioid pills, medicated liquids, or other medications by utilizing a local take-back or mail-back program, or medication drop box at a police station, Drug Enforcement Administration-authorized collection site, or pharmacy (if the pharmacy has a secure drop-box program).

The control of wound pain is an important part of minimizing the suffering from complications of advanced diseases. This implication is paramount to the practicing wound care provider and implies the need to acknowledge the potential harm from the opioids prescribed to their patients during wound care management. It is essential for practice management and reducing risks of evaluating opioid prescribing, monitoring, and facilitating patient education initiatives to mitigate the current opioid crisis. Principles of opioid stewardship and the use of a helpful acronym within the framework of opioid prescribing for wound care management were introduced. Opioid stewardship principles should become a priority in wound management and procedural and operative surgical intervention. 

Author: Robert George Smith, DPM, MSc, RPh

Affiliation: Shoe String Podiatry, Ormond Beach, FL

Correspondence: Robert George Smith, DPM, MSc, RPh, Shoe String Podiatry, 723 Lucerne Circle, Ormond Beach, FL 32174; ASAMAAN@cfl.rr.com 

Disclosure: The author discloses no financial or other conflicts of interest.