Chronic Pain Patients Who Fail Standard Treatment: Now What?
There is a group of severe and chronic pain patients who do not get adequate pain relief despite a clinical regimen that includes non-opioid medications and a daily opioid dosage of 100 mg or more morphine equivalents (MEQ).1-4
Until recently, most of these patients (hereafter called treatment failures) could only be effectively treated by raising the opioid dosage. This often resulted in the administration of high and ultra-high opioid dosages to obtain enough pain relief to enable patients to physically and mentally function, carry out activities of daily living, and attain an acceptable quality of life.
Today, these same treatment goals now can be achieved without resorting to extremely high or ultra-high opioid dosages. Thanks to a new understanding of pain centralization, opioid metabolism, genetic defects, and hormonal relationships to pain control, successful pain relief can usually be achieved, even for these previously considered treatment failures.5-8
New and essential laboratory testing is now available to aid the development and administration of effective treatment strategies for treatment failures. I previously outlined these diagnostic tests in the first of this 2-part series.1 Diagnostic tests include genetic assays, opioid serum levels, neuroinflammatory biomarkers, and hormone profiles (Table 1).
Described here are the strategies used by the author to treat patients who fail 100 mg per day, or more, of MEQ and have 1 of the 4 basic causes of treatment failure (Figure 1). The strategies described have two primary goals: provide enough pain relief to function and carry on activities of daily living, and keep opioid dosages below an ultra-high level.
Treatment Strategy #1: Non-Oral Opioids
Opioid malabsorption is defined as the inability to transport opioids from within the intestinal lumen into the serum.6 When present, it may be a cause of treatment failure. Opioid malabsorption is more common than generally recognized. The symptom hallmark is poor relief with oral opioids. Every patient who fails to get relief with 100 mg or more of MEQ should be evaluated for opioid malabsorption. Common symptoms of malabsorption include bloating, steatorrhea, nausea, and undigested food or medication in stools.
The most common cause of opioid malabsorption is the presence of a gastrointestinal disorder such as diabetic gastroparesis, chronic pancreatitis, and/or chronic disease; as well as multiple abdominal surgeries or adhesions that may disturb the neuronal innervation of the intestine. Other causes include traumatic brain and/or neck injury, because proper function of the vagus nerve is critical for intestinal absorption. Lower spine surgery or injury, hormonal deficiencies, and autoimmune disease also may cause opioid malabsorption. Patients with opioid malabsorption may show low opioid serum levels.
An injectable challenge with an opioid, such as hydromorphone, morphine, or meperidine, will help confirm the diagnosis and help select an effective opioid for treatment.6 It is also important to point out that opioid malabsorption is likely increasing in incidence and prevalence in the population, due in part to the increasing incidence of diabetes, bariatric surgery, and autoimmune disease, among other causes of malabsorption.
Treatment of Opioid Malabsorption
If opioids are not being properly absorbed via the gut, it is important for the clinician to find another route of administration. Several non-oral formulations are commercially available (Table 2). These include transdermal, transmucosal, and injectable opioids. Naturally the underlying cause of malabsorption should be treated, if possible.
Case Example: Gastrointestinal Disorder
A 57-year-old woman has Crohn’s disease and has undergone 28 abdominal/pelvic/rectal surgeries. She had a significant small bowel resection, as well as a total colectomy with rectum removal. She evacuates through an intestinal portal with a syringe. Over several years she developed, in addition to severe abdominal pain, lower spine and fibromyalgia-type pains.
She was referred to my practice and was taking these oral opioids each day: hydromorphone 48 mg; hydrocodone 30 mg; and codeine 60 mg. The patient stated that only oral hydromorphone provided any pain relief, but she was still bed- and house-bound most days each week. She was switched to a regimen of transdermal fentanyl (50 mcg every other day) and injectable hydromorphone (5 to 8 mg) for breakthrough pain. This regimen allowed her to physically and mentally function each day and no longer be bed or house bound.
The problem of opioid malabsorption in this patient had gone unrecognized by multiple practitioners and institutions, even though the severity of her intestinal problem was quite obvious. A history of poor pain relief with oral opioids and the presence of an abdominal or pelvic disorder should always raise a suspicion of opioid malabsorption. This includes previous abdominal or pelvic surgeries, which may leave residual adhesions and/or neuropathies.
Case Example: Traumatic Brain Injury, Spine Degeneration, and Hormonal Deficiencies
A 44-year-old woman sustained a severe fall, which resulted in a concussion and cervical spinal injury. Over a 15-year period she saw numerous physicians and pain specialists who prescribed a variety of oral opioids and non-opioid measures.
She was referred to my practice because all oral opioids had “stopped working,” and she had lost 30 to 40 pounds. She was too weak to ambulate and was bed-bound. At her initial evaluation she had a blood pressure of 87/61 mm/Hg, was emaciated, and had pigmented lesions over her upper trunk, where open, inflammatory skin lesions had developed.
A hormone profile showed pituitary-adrenal insufficiency with a serum adrenocorticotropin (ACTH) level of less than 5 pg/mL (normal 6-50) and cortisol of 1.7 mcg/dL (normal 4.0-22.0). Her oral opioid dosage was 120 mg of hydrocodone each day; however, that regimen provided minimal pain relief for only about 1 hour.
A subcutaneous hydromorphone challenge of 2 mg provided her with immediate pain relief. The patient was started on transdermal fentanyl, 50 mcg every other day, and injectable hydromorphone 2 mg for breakthrough pain. Hydrocortisone was started at 15 mg a day. Within 10 days, her pain was significantly reduced, and she could ambulate and care for herself.
Traumatic brain injury and/or cervical neck trauma may cause autonomic dysfunction due to vagus nerve injury. Proper autonomic neural function is critical for intestinal absorption of opioids. Hormone deficiencies, such as was found in this patient, may also contribute to malabsorption.