University of Saskatchewan
  We have a new website. Click here to view it.
Department Heading

Grand Rounds / Articles

Management of Wound Pain - A Topic in its Infancy

Nora McKee, MD
Assistant Professor
Department of Academic Family Medicine
University of Saskatchewan

Although the range of wound treatment modalities and research in this area have increased, discussion of treatment of the pain associated is relatively absent in the literature. Wound dressings themselves are treatment nightmares because they create incidental pain, one of the most difficult forms of pain to treat. Despite better understanding of the effect of pain on quality of life there remain biases against pain management in general, and a lack of knowledge of the analgesics which are available. This module is intended to provide information on selective use of analgesics and co-analgesics, with examples of clinical situations in which pain management is effective.

After completing this module the physician will be able to:

Why is it a concern?

Practices and predictors of analgesic interventions for adults undergoing painful procedures

A study in the American Journal of Critical Care, September 2002, looks at common hospital procedures, turning, insertion of CVP, suctioning, removing drains and changing dressings on non-burn wounds.

Conclusions:

Clinical examples:

  1. A 47 year old Caucasian with mycosis fungoides causing extensive skin lesions
    - Journal of Pain and Symptom Management   July 2001
  1. A 21 year old woman with pelvic sarcoma

Barriers to studying wound pain

The Nature of Pain

Assessment of pain requires an understanding of:

Physiology of pain

Types of pain

Nociceptive pain
Neuropathic pain
Wound Pain

Chronic pain with incidental acute exacerbations (i.e. dressing changes), can be inflammatory since often related to infection, can be neuropathic with cutaneous nerve involvement, is often associated with anxiety and anticipatory pain, and is accompanied by significant psychological impact related to altered body image, shame or depression.

Management

* Don't Delay for Investigations or Disease Treatment*

Unmanaged pain gives rise to nervous system changes which can produce permanent damage and amplify pain

Figure - WHO Analgesia Ladder

Acetaminophen

Analgesic, co-analgesic, site and mechanism of effect unknown, has minimal anti-inflammatory effect.

Risk. Hepatic toxicity if > 4gm/24 hours
Increased Risk. Hepatic disease and heavy alcohol use.
NSAIDS

Analgesic, co-analgesic, inhibits cyclo-oxygenase (COX), variable COX-2 selectivity. All have analgesic ceiling effect, effective for bone and inflammatory pain with individual variation demonstrated in serial trials.

Risk. Renal insufficiency (must maintain adequate hydration)
G-I bleeding (COX-2 selection inhibitors)
Inhibition of platelet aggregation.(assess for coagulopathy)
Opioids

Effective step 2-3 medications with manageable and predictable side effects. Many fears and biases exist among patients and caregivers related to opioid use, and training program offer little education in their use.

Breakthrough Dosing;

Use immediate release opioids 5-15% of 24-hour dose
Offer after Cmax reached

p.o./p.r. q 1h
s.c./i.m. q 30 mins
i.v. q 10-15 mins

Opioid concerns

Addiction
Represented by psychological dependence, compulsive and continued use despite harm, loss of control over drugs, loss of interest in pleasurable activities.

This is a rare outcome of pain management, particularly if there is no history of substance abuse.

Consider

Tolerance
Reduced effectiveness of a given dose over time, this is not clinically significant with chronic dosing, but disease progression should be considered.

Equianalgesic Doses
   
Morphine 100 mg/day
Dilaudid 20 mg/day
Fentanyl 25 ug/hr q72hr
Codeine 1000 mg/day
Oxycodone 50 mg/day
Methadone 10 mg/day
Demerol 1000 mg/day

Specific Opioids

Morphine
Prototype opioid most familiar and available in most presentations (oral, parenteral, rectal). It is orally well absorbed and metabolized in liver to Morphine-6-glucuronide( a potent analgesic at opioid receptors) and Morphine-3-glucuronide (neurotoxic, in renal failure accumulates leading to delirium and myoclonus).

Demerol
Synthetic opioid with the same agonist effects as Morphine but more severe potential side effects. Its active metabolite, norpethidine, has twice the potency as a convulsant and half the analgesic effect of the parent compound. Repeated doses lead to accumulation, especially in renal failure, and side effects include tremor, myoclonus and seizures which are not reversed by narcan. Demerol is not used in the management of chronic pain.

Codeine
Usually combined with a non-opioid, less potent than morphine with less affinity for receptors, must be biotransformed to morphine and therefore ineffective in the absence of cytochrome P450 2D1. Codeine is available in a sustained release formulation. Well known side effect is constipation.

Hydromorphone
Semi-synthetic opioid which is 5 times as potent as morphine, more soluble (i.e. useful in injectable form) and in the opinion of some experts has fewer side effects than morphine.

Fentanyl
Strong, highly lipophilic short acting synthetic opioid which is available as an injection or a patch. The patch has a delay in onset of analgesic effect, and a skin depot remains after removal, also if it doesn't stick it doesn't work. Fentanyl is not ideal for titrating dose and has a suggested ceiling of 600-700 mcg/hr. It's metabolites may be inactive. For breakthrough pain use morphine or dilaudid.

Oxycodone
Given usually as combination product with ASA or acetominophen, but is a strong opioid when used alone and is available in a sustained release format. Regarded as a drug of abuse in USA.

Methadone
Inexpensive, synthetic opioid developed in 1940s in Germany, which is closer to heroin than to morphine and acts at mu and NMDA receptors. It has a long and unpredictable half-life. N-methyl-aspartate antagonism is important to stop paradoxical and "wind-up" pain. A reservoir effect is noted. Methadone comes either as a powder to be mixed or as a prepared solution, although its bitter taste has to be disguised (e.g. in Tang or chocolate sauce). Its equianalgesic dose is poorly defined and there is variable cross tolerance.

Adjunct Medications

Adjunct medications are needed to avoid the need to increase opioid doses to the level at which side effects can be intolerable. Tricyclic antidepressants and anticonvulsants are effective in neuropathic pain and act at the sodium channel, blocking the nerve's transmission of pain.

Gabapentin
Of the anti-convulsants gabapentin is a newer, voltage sensitive sodium channel antagonist with possible effects on subunits of the calcium channel. Animal studies showed effect on post-operative pain, and studies using healthy volunteers have shown that gabapentin enhances the analgesic effect of morphine. It may also have an anxiolytic effect. Gabapentin has a definite effect in neuropathic pain, and some claim effect in inflammatory pain also. It is available in 100,200,300,400 and 600mg tablets, and can be titrated up tot 4000mg/day starting at 100-300mg tid and titrating up at 48hr intervals. Gabapentin is relatively fast acting and well tolerated with few side effects, although rapid titration can lead to sedation. There is no known organ toxicity or significant interaction with other drugs, although caution should be used with methadone . It is expensive.

Topical Opioids
In 1774 Heberden noted that "patients with hemmorrhoids should apply a mixture of a dram of the softened extract of opium for pain so excessive as to require immediate relief", he speculated that the opium was working topically since there were so few central CNS effects. In 1885 Wood wrote that morphine elicited analgesia when administered topically to painful sites in the peripheral tissues.

Traditionally it was believed that opioids worked centrally at the dorsal ganglion causing analgesia, sedation, respiratory depression and antitussive effects. Peripheral effects, such as constipation, nausea and vomiting were thought to be due to receptors outside the blood-brain barrier. Opioid receptors have been found in immune cells, peripheral nerves, inflamed tissues, lungs and cardiac muscle.

There is data to suggest that the opioid receptors are manufactured in the dorsal root ganglia, and transported peripherally along the axons. They seem to be activated by inflammation, since absorption is poor through intact epidermis. Serum and urine testing for morphine glucuronides reveals no detectable amounts and systemic effects seem minimal. Stein, in 1991 proved that peripheral receptors were present in inflamed synovial tissue by injecting 1 mg morphine into the knee joint after menisectomy, providing prolonged post-operative analgesia.

Clinical examples:

  1. A 55 year old woman with melanoma
  1. A 67 year old man with Prostate Cancer
  1. An 80 year old man with ALL
  1. A 56 year old man with Rectal Cancer
  1. A 71 year old woman with Ovarian Cancer

Sublingual Fentanyl / Sufentanil

Sufentanil has 5-7 times the potency of fentanyl and is rapidly absorbed through mucosal membranes with onset of action 3-5 minutes lasting 20-30 minutes. The same solution used intravenously in anesthesia is used sublingually and is best used for incidental pain such as transfers, dressing changes, debridement etc. It is supplied in ampoules of 1 and 5 mls (1ml=50mg sufenta). The dosage starts at 0.1ml (5mcg) if the patient is regularly using less than 500mg morphine equivalent, 0.2 mls if regular dose is higher.(Victoria Hospice protocol). In the United States Fentanyl is available in lollipop formation for incidental pain.