Introduction and Problem Statement (1)

September 20, 2020

Intrathecal Medications for Chronic Pain

A selected topic from the approved list: Implementing a clinical practice protocol/guideline for pain control in chronic pain patients.

PICOT: In chronic pain patients (P), can an intrathecal ketamine program (I), compared to an intrathecal morphine program (C), improve pain control (O) over three months (T)?

Epidemiologists have found chronic pain in people across the world, it is often difficult to treat, and it originates from the body, the brain, or the spinal cord (Wikipedia, 2020). Selby (2020) states that chronic pain is characterized as pain that persists for at least three months. From arthritis to cancer pain, there are a multitude of causes for chronic pain. Greater than 50 million adults are affected by chronic pain in the United States (US) (Selby, 2020, para. 1). The cost of chronic pain exceeds $635 billion annually in the US (Selby, 2020, para. 1). The need for pain management and pain management research will become even more imperative as medical providers continue to see an increase in our aging population, individuals with diabetes, and cancer survival rates (Selby, para. 2). Therefore, it is imperative that the health care industry be interested in finding alternative ways to treat chronic pain. One alternative method is the use of intrathecal (IT) medications.

According to Hatheway et al. (2019), the ongoing epidemic of drug misuse, addiction, and death from overdoses continues to create a dynamic public health crisis within the US (para. 1-2). The attempts to minimize diversion, abuse and addiction by severely restricting the availability of legal, prescription opioids have negatively affected chronic pain patients and guided the growing usage of illicit opioids (Hatheway et al., 2019, para. 1-2). An essential objective that cannot be overlooked or lost during discussions on how to gain control of the opioid epidemic is how to provide chronic pain patients the necessary medications they need for pain relief (Hatheway et al., 2019, para. 1-2).

Prescription opioids are used to help manage chronic intractable pain. The Centers for Disease Control and Prevention states that before starting opioid medications, practitioners consider nonopioid pharmaceuticals such as acetaminophen, ibuprofen, some antiseizure, and antidepressant medications to help control chronic pain (CDC, n.d.). In addition, practitioners can include physical therapy, acupuncture, massage, and cognitive behavioral therapy (CDC, n.d.). However, at times nonopioid treatments fail, and opioids are introduced. But for some patients, even opioids do not control their pain, and the patient continues to experience pain at a high level where the patient is unable to perform his/her activities of daily living (ADLs). When this occurs, another form of treatment needs to be considered, including continuous IT (spell out) medication therapy.

For more than 30 years, medicine has been using continuous IT drug delivery systems (Shaparin et al., 2005, p. 166). The use of IT drugs, while an underutilized resource, can provide patients with spasticity and refractory chronic pain relief with lower medication doses and fewer side-effects (Shaparin et al., 2015, p. 166). Per personal conversation with Rosenblum, S. (2019) IT medications are delivered into the spinal canal via a small programmable pump that is surgically implanted by a neurosurgeon. The IT pump is implanted under the subcutaneous tissue. Placement is generally in the abdomen but can be in the flank area, depending on the neurosurgeon’s preference. A small catheter from the pump is connected to a site in the spinal canal. The pump is filled with medication and must be refilled, usually every three months, either in the practitioner’s office or at the patient’s home by a trained home health nurse (S. Rosenblum, personal communication, November 10, 2019).

Problem Overview

“The US Food and Drug Administration (FDA) has approved three medications for continuous IT delivery: morphine, ziconotide, and baclofen” (Shaparin et al., 2015, p. 168). However, other medications such as other opioids, local anesthetics, or alpha 2-adrenergic agonists have been used and tested for IT pain management (Shaparin et al., 2015, p. 168). This paper will focus on IT morphine and IT ketamine.

Morphine, which is an opioid, has been FDA approved for use as an IT medication to be used for chronic pain control. When morphine is used as an IT medication, the effect of the analgesia is more pronounced, and it also exhibits fewer side-effects than systemic opioids (Shaparin et al., 2015, p. 168). While giving IT morphine does appear to have its benefits; it is not devoid of complications. IT morphine has been associated with “respiratory depression, constipation, urinary retention, nausea/vomiting, sweating and hyperalgesia” (Shaparin et al., 2015, p. 169). None the less, IT morphine has been an innovative way of providing pain relief to chronic pain patients for many years who would have been suffering with oral opioids.

Since the 1960s, ketamine has been used as an anesthetic agent (Bell & Kalso, 2018, para. 2). Ketamine has been used in emergency departments and operating rooms. It is also used for chronic non-cancer pain that has become opioid resistant, and most recently, has been used to treat major depression and mood disorders (Bell & Kalso, 2018, para. 1). While ketamine is best known for its anesthetic effects, it also has anti-inflammatory effects, and “its beneficial interaction with opioids, including reduction of opioid tolerance, makes it an especially interesting drug for use in pain management” (Bell & Kalso, 2018, para. 4). However, one of “the most commonly reported adverse effects from ketamine are psychotomimetic (hallucinations, agitation, anxiety, dysphoria, and euphoria). Administration of ketamine may also cause dizziness, nausea, sedation, and tachycardia.” (Bell & Kalso, 2018, para. 6).

According to Benrath et al. (2005), there is limited use of ketamine in chronic pain patients due to unpleasant adverse effects and low enteral absorption with continuous IV infusion. However, IT ketamine administration is a rarely used alternative (p. 247). Breadleau et al. (2013) stated that per their review, which included five randomized controlled trials (RCTs) and six prospective uncontrolled trials of ketamine for cancer pain in adults, there was concern expressed regarding the administration of IT and spinal ketamine due to the adverse effects of neurotoxicity and that it should be avoided (as cited by Bell & Kalso, 2018, para. 3). Concerns regarding the neurotoxicity of ketamine have been brought to the attention of the medical community through studies and reports which have indicated that neurological lesions may be caused by the preservative benzethonium chloride or chlorobutanol, which is used in the racemic ketamine solution. Although, the S(+)-Ketamine solution, also available for administration, is preservative-free and appears to be suitable for IT administration (Benrath et al., 2005, p. 249).

While the knowledge and expertise regarding IT medications continue to evolve, health care practitioners need to continue to expand their horizons regarding treatments and remedies for chronic pain control. This knowledge would include knowledge and experience with IT ketamine. While the early reports have indicated presumed neurotoxicity with IT ketamine, there have also been indications of beneficial clinical outcomes, including reductions in systemic opioid doses. While there is no real consensus among the medical community regarding the role of IT ketamine therapy and its role in chronic intractable pain control, one may beg to ask the question if it is time to determine if IT ketamine therapy would present an additional alternative for hundreds of individuals who are needlessly suffering from chronic intractable pain.

References

Bell, R. F., & Kalso, E. A. (2018). Ketamine for pain management. Pain Reports, 3(5), e674. 10.1097/pr9.0000000000000674