10.18.2024

Pain Management: Back to the Basics

PATIENT CASE 

KP is a 66-year-old female with metastatic breast cancer and gastroesophageal reflux disease, who has recently been admitted to hospice.

Current medications:

  • Famotidine (Pepcid®) 20mg; 1 tablet by mouth every day for the stomach
  • Haloperidol (Haldol®) 0.5mg; 1 tablet by mouth every 6 hours as needed for nausea or vomiting
  • Levetiracetam (Keppra®) 500mg; 1 tablet by mouth twice a day for seizure control
  • Lorazepam (Ativan®) 0.5mg; 1 tablet by mouth every 6 hours as needed for anxiety
  • Oxycodone-acetaminophen (Percocet®) 5/325mg; 2 tablets by mouth every 4 hours as needed for pain

During the initial assessment, she reported persistent pain throughout the day and night, describing it as a dull pain and pressure in her bones, along with pronounced discomfort throughout the surrounding areas. KP’s pain has progressively worsened over the past month. She is prescribed oxycodone-acetaminophen (Percocet®) and initially the medication was effective, but its efficacy has diminished over time requiring the use of 5 doses per day with only partial relief. She reports no other symptoms besides the occasional nausea, which is adequately managed with her haloperidol.

PAIN TYPES

Pain can be categorized into three types: nociceptive pain, neuropathic pain, and mixed pain. Since pain is a subjective experience, accurately describing how the patient experiences it is crucial for proper classification and treatment.

Nociceptive pain signals potential tissue damage and is further divided into somatic and visceral pain:

  • Somatic pain is described as dull, throbbing, or aching. It is well-localized, often worsens with movement, and usually occurs in bones, joints, connective tissue, muscles, or on the skin. Examples include pain from bone metastases, muscle spasms, incisions, and cellulitis.
  • Visceral pain is described as deep, squeezing, pressure, or cramping. It is more diffuse and harder to localize, often referred to other areas of the body. It typically arises from internal organs, such as the heart (e.g., myocardial infarction with referred pain to the left arm), pancreas (e.g., pancreatitis), and the gastrointestinal tract (e.g., peptic ulcer, bowel obstruction).

Neuropathic pain may be described as burning, electric, shooting, tingling, or stabbing. It arises from activation of the pain pathways due to nervous system damage and is further categorized into central and peripheral pain:

  • Central pain originates from the spinal cord and includes conditions like spinal cord injury, encephalitis, and myelitis.
  • Peripheral pain occurs in the limbs and can be caused by diabetic neuropathy, herpes zoster, or exposure to toxins.

Mixed pain combines features of nociceptive and neuropathic pain, and patients, especially at the end of life, may experience a blend of these types. Patients with cancer commonly present with mixed pain (e.g., bone pain; obstruction of a bile duct, ureter, or bowel lumen; mucositis; spinal cord compression; or several types of neuropathies).1

ASSESSMENT

A thorough pain assessment provides insight into the patient’s experience. Only the patient can describe the pain they experience, however factors such as age, communication barriers, cognitive impairment, and substance abuse history may affect accurate assessment.2

  • Assessments should also include observations of verbal and non-verbal cues, body movements, interpersonal interactions, changes in routines, and mental status.
  • Assessments should be conducted upon admission, with each new report of pain, and at regular intervals after initiating treatment.

Single-dimensional scales are simple to use and allow patients to rate one aspect of their pain, typically the intensity. They may be useful in acute pain when the etiology is clear (e.g., trauma, injury). However, they can oversimplify the pain experience and results vary among different patient populations diagnoses. The three most utilized tools to quantify pain intensity include verbal rating scales, numeric rating scales, and visual analogue scales.2 Examples include The Numeric Pain Intensity Scale (NPIS)/Visual Analog Scale (VAS),3 Simple Descriptive Pain Distress Scale,4 and Faces Pain Rating Scale.5

Multi-dimensional tools, like the PQRSTU mnemonic6 below, are structured for gathering relevant information and may aid patients in describing their pain more effectively.

Other multi-dimensional assessment tools may be appropriate based on patient-specific factors:

  • For pediatrics, the FLACC Pain Assessment Tool has been validated for use in patients aged 2 months to 7 years and uses a scale of 0-2 for each of five categories: Face, Legs, Activity, Crying, Consolability7-9
  • For infants, the CRIES scale uses 5 variables (Crying, Requires oxygen, Increased vital signs, Expression, Sleeplessness) on a scale of 0-2 points to assess neonatal postoperative pain 2,7,10
  • For patients with dementia or cognitive impairment, the PAINAD (Pain Assessment IN Advanced Dementia) Scale2,11-13 is an observational tool made up of five items: Breathing, negative vocalizations, facial expression, body language, and consolability

MANAGEMENT

Once a thorough pain assessment is completed and therapy goals are established, treatment can be tailored to the patient’s specific needs. The focus should be on relieving pain while preserving function, minimizing side effects, and using cost effective options, including both non-pharmacologic and pharmacologic treatments.

Non-pharmacologic treatment is recommended when appropriate. These therapies include:14,15

  • Heat or cold therapy
  • Physical and occupation therapy
  • Massage
  • Psychological therapy such as cognitive behavioral therapy (CBT)
  • Mind-body therapy (e.g., meditation)
  • Spiritual counseling
  • Aromatherapy
  • Music therapy

Non-opioids: 16-18

Guidelines from organizations such as the World Health Organization (WHO) recommend non-opioids as initial pharmacotherapy for pain,16  but they can be employed at any stage of management used alongside opioids to enhance analgesia while reducing overall opioid use.

Opioids:17-20

Opioids are commonly used to manage moderate to severe pain and dyspnea in palliative care. They are typically employed when non-opioids fail to provide adequate relief. For patients with severe, progressively worsening conditions, opioid doses may be titrated based on patient tolerance, with no maximum dose or daily use limit. Opioids may only partially relieve inflammatory and neuropathic pain, necessitating concurrent administration of adjuvants for effective pain management.

For Opioid-Naïve Patients

  • Initiate treatment with an appropriate starting dose of an immediate-release opioid (see table below)
  • Effective pain management requires ongoing assessment and adjustment to address evolving patient needs (e.g., change in status, disease progression)
    • Regularly measure efficacy by assessing pain relief and increase dose by 25% for unrelieved pain
    • Regularly assess tolerability (any new and/or worsening adverse effects, such as nausea, vomiting, constipation, drowsiness) and decrease dose by 25% for intolerable adverse effects or consider changing to a different opioid
  • When immediate-release “as needed” opioids are used consistently (i.e., using ≥ 3 doses per day for ≥ 48 hours to manage pain):
    • Consider adding a long-acting opioid formulation to lessen pill burden; keep the “as needed” therapy as breakthrough (i.e., rescue) medication
    • Initiate a new as-needed dose by calculating 10-20% of the total daily long-acting opioid dose. For example:
      • Morphine long-acting 30mg, 1 tablet by mouth twice daily (= 60mg morphine per day)
      • 10-20% of 60mg = 6mg to 12mg morphine per dose
      • New breakthrough regimen: morphine 20mg/ml liquid, 0.5ml (10mg) by mouth every 4 hours as needed

For Opioid-Tolerant Patients

Assess current pain regimen using the PQRSTU mnemonic (e.g., Is the pain controlled? Any intolerable adverse effects? On a long-acting or short-acting opioid or both? How much of the “as needed” medication has been taken in past 24 hours?)

  • For stable pain control and:
    • Tolerating regimen: Continue current regimen
    • Not tolerating regimen: Consider changing to another opioid (i.e., opioid rotation) and/or managing adverse effect (e.g., prescribing a stimulant laxative for constipation)
  • For unstable pain control and:
    • Tolerating regimen: Consider increasing current opioid by a percentage (e.g., 25%)
    • Not tolerating regimen: Consider changing to another opioid and/or manage adverse effect that is limiting dose escalation

Opioid Rotation and Equianalgesic Opioid Dosing

Equianalgesic opioid dosing tables (conversion tables) list opioid doses that provide approximately the same analgesic response based on potency (drug amount needed to produce an effect) and bioavailability (drug amount detected in the system, after taking the drug, which is available to provide pain relief).6

It is important to remember that equianalgesic data is based on the best evidence available however are only approximations and do not replace clinical judgment.6 Doses need to be individualized based on factors such as current pain control, opioid tolerance, and organ function. Increased opioid sensitivity seen when switching between opioids (i.e., incomplete cross-tolerance) must also be considered however this and other nuances of opioid conversion are beyond the scope of this article.

The table below6 is not comprehensive of all opioids that have equianalgesic data; it represents a sampling of opioids commonly used in initial opioid regimens that are simplest to convert. For example, morphine and oxycodone are two different opioids that provide approximately the same degree of pain relief when given orally at 25mg and 20mg doses, respectively.

Contact a pharmacist or experienced clinician for guidance on conversions, especially those involving methadone and fentanyl. Methadone dosing is highly variable.6 There exist several dosing methods for converting to methadone for pain. The suggested conversion from transdermal fentanyl (TDF) (Duragesic®) to oral morphine is 1:100 (1mg/day TDF is equivalent to 100mg/day of oral morphine). However, there is no known reliable equianalgesic conversion data for fentanyl immediate-release products (e.g., Actiq®, Abstral®) to or from other opioids.

Partial or No Response to Opioid Therapy

Some patients may be only partially responsive to opioid therapy alone. This may present as unrelieved pain despite opioid titration, inability to titrate due to adverse effects, or no additional pain relief when switching to another opioid. Adding an adjuvant analgesic may be considered for these patients.23

Adjuvants:17,18

Adjuvants are a diverse group of drugs, most of which were originally indicated for medical conditions other than pain. Through clinical experience they have gained new indications (labeled and off-label) for pain relief, either in combination with analgesics or on their own. By targeting different pain pathways, these agents can reduce pain severity, thereby allowing for lower opioid doses (when used concomitantly) and minimizing adverse effects. When integrating adjuvants into a pain regimen, it is essential to consider their side effect profiles, and potential drug-drug and drug-disease interactions.

PATIENT CASE ASSESSMENT

Based on KP’s presentation of pain, the hospice team conducted a thorough assessment using the PQRSTU mnemonic.

PATIENT CASE RECOMMENDATIONS

Details obtained from a thorough assessment provide the most informed and patient-specific recommendations. For KP, they include:

  1. Initiate therapy for somatic bone pain. Corticosteroids provide anti-inflammatory effects, increase energy to preserve KP’s function, and have antiemetic effects that may benefit her occasional nausea.

Recommend dexamethasone 4mg tablet by mouth twice a day for bone pain.

  1. Initiate long-acting opioid therapy. We know that KP’s pain is responsive to opioids however she needs around-the-clock continual pain coverage to reduce the frequency of breakthrough pain episodes.

Recommend morphine extended-release (MS Contin®) 30mg tablet by mouth every 12 hours for pain.

  • KP previously used 50mg of oxycodone per day (5 doses/10 tablets per day) from the oxycodone-acetaminophen.
  • Equianalgesic tables suggest 50mg of oral oxycodone is equivalent to approximately 60mg of oral morphine per day using a 25:20 morphine:oxycodone ratio. Since morphine extended-release has a duration of action of 8 to 12 hours, a dose of 30mg every 12 hours provides 24-hour pain coverage.
  • The dose of morphine is “equal” to the dose of oxycodone that only provided partial pain relief, the patient may not have the same opioid tolerance when rotated to the new opioid (incomplete cross-tolerance). Using an additional percentage decrease in dose (25%) of the new opioid (in this case, morphine) lessens the risk. For KP, an empiric 25% increase in dose to account for uncontrolled pain cancels out a 25% decrease for incomplete cross-tolerance.
  1. Replace oxycodone-acetaminophen with morphine 20mg/ml (Roxanol®) immediate-release oral concentrate. Morphine can be titrated as high as the patient will tolerate without limits from combination with a non-opioid analgesic (e.g., acetaminophen). Acetaminophen was likely not contributing to pain relief and does not need to be replaced or added back as a single agent.

Recommend Morphine 20mg/ml; 0.5ml (10mg) by mouth every 4 hours as needed for breakthrough pain.

  • Breakthrough medication dose is 10-20% of 60mg/day, or 6-12mg/dose.
  • Breakthrough medication provides rapid-onset symptom relief when the long-acting pain regimen does not provide sufficient relief.
  • Monitored use provides the first indicator of pain progression and need for long-acting dose titration.
  • Morphine immediate-release was chosen because it is the same medication as the long-acting regimen, making future dose titrations simpler.
  1. Incorporate a prophylactic bowel regimen. Constipation is an inevitable adverse effect of opioid therapy of which patients do not grow tolerant. Proactively manage with scheduled doses of stimulant laxative such as bisacodyl or senna for the duration of opioid therapy.

Recommend bisacodyl 5mg tablet (Dulcolax®); 1 tablet by mouth every day for constipation.

  1. Successful pain management is an ongoing process. Sometimes doses/therapies that were once helpful may lose effectiveness due to disease progression and patient-specific factors.

Reassess therapies regularly to optimize care.

  • Measure efficacy by assessing pain relief using the PQRSTU mnemonic; for unrelieved pain increase dose empirically by 25% or based on breakthrough medication use.
  • Assess tolerability (any new and/or worsening adverse effects such as nausea, vomiting, constipation, drowsiness) and decrease dose by 25% for intolerable adverse effects or consider opioid rotation.

ENCLARA RESOURCES ON PAIN MANAGEMENT

 

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REFERENCES

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