TABLE 1: Pain Classification by Duration of Symptoms
|
|
1: ACUTE
- 0-7 days duration
- Mild to severe
- Etiology known or unknown, usaually a single, "fixable" event
- Input from nociceptors (peripheral pain receptors)
- Treatment of causes and pain reduction: often an emergency
- Analgesics: Narcotic and non narcotic
- Mild psychological contribution
2: SUBACUTE
- 7 days to 6 months duration
- Mild to severe
- Etiology same as acute pain
- Input from nociceptors
- Treatment of causes and pain reduction: usually not an emergency
- Mild psychological contribution
3: ONGOING ACUTE
- Any duration of time
- Usually severe
- Due to ongoing tissue damage from neoplasms
- Input from nociceptors
- Treatment of causes and pain reduction
- Analgesics: Narcotic and non-narcotic
- Depression and anxiety common
|
4: RECURRENT ACUTE
- Any duration of time
- Mild to severe
- Due to chronic organic non-malignant pathology
- Input from nociceptors
- Treatment of causes and pain reduction
- Analgesics: Non-narcotic and co-analgesics as first line
- Narcotics sometimes indicated
- Depression and anxiety common
5: CHRONIC BENIGN
- Greater than 6 months duration
- Mild to severe
- Etiology unknown
- No known nociceptor input
- Treatment aimed at pain reduction
- Non-narcotic and co-analgesics are primary medications
- Usually no indication for narcotics
- Psychological factors very important, psychotherapy indicated
- Patient may or may not have adequate coping mechanisms
|
Effective management of pain
The clinical management of all pain syndromes should begin with an attempt to identify and
treat the underlying cause of the pain. On occasion -- especially in patients with well advanced HIV
disease who suffer from concurrent infections and/or neoplasms -- the underlying cause of a patient's
pain cannot be identified or cannot be treated. Fortunately, this situation does not pre'mpt
effective pain management; it simply shifts the focus of treatment from the cause to the pain itself.
"Regardless of cause, the objective of pain treatment is threefold: to reduce the patient's discomfort,
decreased his anxiety, and return him to his previous level of function. There are no easy formulas to
achieve these objectives. Treatment must always be individualized, because patients exhibit a remarkably wide
range of pain tolerance and an equally wide range of responsiveness to pharmacotherapy."
|
Regardless of cause, the objective of treatment is threefold: to reduce the patient's discomfort,
decreased his anxiety, and return him to his previous level of function. There are no easy
formulas to achieve these objectives. Treatment must always be individualized, because patients
exhibit a remarkably wide range of pain tolerance and an equally wide range of responsiveness to
pharmacotherapy.
The vast majority of all complaints of pain arise from acute and subacute causes. Here the
underlying problem is usually tissue injury, either from intrinsic or extrinsic causes. For
these forms of pain, the essence of effective clinical management is to provide good analgesic
support while the body has time to repair itself.
Chronic malignant and non-malignant pain with ongoing tissue injury is categorized as ongoing or
recurrent acute pain. Pain in AIDS is often a combination of the two. For these patients it is
imperative to follow the pain analgesic ladder that the World Health Organization developed for
cancer patients in 1990. Each step in the ladder represents a further step in the pharmacologic
management of the patient's pain, steps necessitated by progression of disease or progression of
symptoms (Figure).
The WHO analgesic ladder does not take into account neuropathic pain, from which many AIDS patients
suffer, either as a direct result of some disease process or as an indirect result of antiretroviral
therapy . Therefore medications that reduce the pain associated with neuropathies should be
used in all affected patients.
"The ideal way to use narcotics is to titrate them to the desired level of efficacy, on a case-by-case basis.
The major limiting factor in increasing narcotic doses is the escalation of undesirable side effects (such as
constipation, sedation, respiratory suppression, and confusion). When narcotics are used for the treatment of
pain, it is unlikely that habituation will become a factor."
|
At the first rung of the WHO ladder are non-steroidal anti-inflammatory drugs and aspirin (Table 2).
NSAIDs reduce pain by decreasing prostaglandin synthesis, relieving mild to moderate inflammation,
and exerting an antipyretic effect. Aspirin, because of its long history of safety and effectiveness,
has been the prototype against which all NSAIDs have been judged. These agents have a ceiling effect,
a dose above which there is no additional benefit, but they also have no tolerance limits or addiction
potential. These drugs have roughly the same activity when given in equipotent doses. The major
limiting factors are adverse reactions and convenience of dosage schedules.
Acetaminophen, which is marketed under many trade names, is not a NSAID. Although it is an antipyretic agent,
it has no peripheral anti-inflammatory or prostaglandin inhibitory activity. It does, however, have analgesic
properties, probably through CNS activity. The usual dose is 650-1000 mg every 4-6 hours by mouth or
per rectum, with a maximum daily dosage of 6-8 grams. It can be given in conjunction with NSAIDs and
narcotic analgesics (whose activity it can potentiate).
Management of mild-to-moderate pain
Many narcotic analgesics can be used to treat mild-to-moderate AIDS-related pain (Table 3). In outpatient
situations, the most convenient route of administration is via the GI tract (oral or rectal). This route has
the added benefit of preventing abrupt swings in serum levels, providing a slow onset and slow decay. Care must
be taken when giving parenteral narcotics that adequate time is allowed for gastrointestinal absorption -- which
can take up to 90 minutes. Repeat doses should be given well before serum drug concentrations drop to
subtherapeutic levels.
"The therapeutic goal of any analgesic regimen sis to achieve an adequate serum level, one sufficiently high
to assure pain relief in the resting state, with additional medication readily available to provide analgesia
for breakthrough pain. Doses should be spaced well within the drug's serum half-life, to maintain
effective serum levels. This is most easily accomplished by providing medication on a fixed schedule for
background analgesia."
|
The ideal way to use narcotics is to titrate them to the desired level of efficacy, on a case-by-case basis.
With the important exceptions of meperidine, propoxyphene and pentazocine, there are no peak doses for narcotics,
as there are with NSAIDs. The major limiting factor in increasing narcotic doses is the escalation of
undesirable side effects (such as constipation, sedation, respiratory suppression, and confusion). When
narcotics are used for the treatment of pain, it is unlikely that habituation will become a factor.
In any case, the spectre of addiction should not be a consideration in the use of these analgesics if they
are deemed necessary for the management of pain in late-stage HIV disease.
The therapeutic goal of any analgesic regimen sis to achieve an adequate serum level, one sufficiently high
to assure pain relief in the resting state, with additional medication readily available to provide analgesia
for breakthrough pain. Doses should be spaced well within the drug's serum half-life, to maintain
effective serum levels. This is most easily accomplished by providing medication on a fixed schedule for
background analgesia. Additionally, some rapid-onset medication should be available for breakthrough pain
on an "as needed" basis.
The longer-acting narcotic analgesics are the logical choice for background analgesia because they achieve
extremely stable serum narcotic levels with only a few doses per day. The same effect can be attained with
the shorter-acting narcotics, but they require frequent dosing. These shorter-acting narcotics do provide
good coverage for breakthrough pain, however.
"In the clinical management of intractable long-standing pain , there is no specific dose of opiate,
and no ceiling above which further dosing is inadvisable. Therefore, the opiate dose should be pushed to
whatever level it takes to make the patient comfortable -- especially at the end of life."
|
Management of moderate-to-severe pain
Narcotic analgesics are rarely used for mild pain, but they are frequently used in cases of moderate to severe
pain. Pharmacologically, they are of two classes: pure opiate-receptor agonists, and mixed agonist-antagonists
that have some properties of naloxone (an opiate-receptor antagonist) mixed with the direct agonist properties.
The prototype pure receptor agonist is morphine, although there are many drugs in this class (see the PULL OUT
AND SAVE feature). The mixed agonist-antagonist analgesics have been slow to achieve popularity for several
reasons: a ceiling effect for analgesia, reversal of analgesia in patients who are also taking pure agonists,
and the unavailability of oral preparations.
For the sustained pain from which many patients with end-stage AIDS suffer, it is most appropriate to use a
sustained-release narcotic analgesic. The specific agent chosen is less important than the principal that
maintaining a therapeutic blood level of opiate is the most appropriate treatment for long-standing pain.
In order to avoid overdosing, the sustained-release opiate should be dosed for analgesia with the patient at
rest. Incident or breakthrough pain can then be treated with small doses of immediate-release short-acting
opiates.
In this context it is important for the care-provider to remember that opiates should be given in escalating
doses until the desired effect is achieved. Side effects are the only limiting factor. In the clinical
management of intractable long-standing pain , there is no specific dose of opiate, and no ceiling
above which further dosing is inadvisable. Therefore, the opiate dose should be pushed to whatever level
it takes to make the patient comfortable -- especially at the end of life.
"For the sustained pain from which many patients with end-stage AIDS suffer, it is most appropriate to use a
sustained-release narcotic analgesic. The specific agent chosen is less important than the principal that
maintaining a therapeutic blood level of opiate is the most appropriate treatment for long-standing pain.
In order to avoid overdosing, the sustained-release opiate should be dosed for analgesia with the patient
at rest."
|
Neuropathic pain may be resistant to opiate dosing alone. For severe neuropathies, the dose of opiate should
be titrated upwards, but adjuvant drugs should be used concomitantly. Neuropathic pain syndromes are managed
first with a tricyclic antidepressant (TCA) given once daily, usually at bedtime (Table 4).
It is important for AIDS patients to lead as normal a day/night cycle as possible, and these drugs not only
help manage neuropathic pain, they are for the most part sufficiently sedating to be used as a sleep aid as well.
Although amitriptyline as generally regarded as the first-line TCA, the anticholinergic side effects and excess
sedation of this and the other first-generation TCAs, doxepin and imipramine, limit their usefulness. Most
patients find nortriptyline or desipramine to be as effective as the first generation TCAs in controlling
neuropathic pain, and they usually experience fewer deleterious side effects. This increases compliance
and, with it, effectiveness.
In many cases of AIDS-related neuropathic pain, a TCA alone proves inadequate, and additional agents must be
started (Table 5). Antiseizure drugs such as carbamazepine and phenytoin can be helpful,
but both have significant side effects and toxicities which can make their use inadvisable, especially at
very sick patients. A newer antiseizure agent, gabapentin, holds great promise of diminishing neuropathic
pain with a minimum of side effects. Clonazepam, a benzodiazepine antiseizure drug, can be very potent,
especially when used in combination with gabapentin.
"It is within the ability of current clinical practice to deliver a high degree of pain control to most
patients with end-stage HIV disease -- without sacrificing their sense of self and their ability to think
and function. In the vast majority of cases, carefully considered titration of medication can result
in a satisfactory outcome, one that ablates the patient's pain and maintains his dignity and comfort."
|
Conclusion
It is within the ability of current clinical practice to deliver a high degree of pain control to most patients
with end-stage HIV disease -- without sacrificing their sense of self and their ability to think and function.
In some patients, more invasive techniques may be needed, including spinal narcotics and destructive nerve-block
procedures. However, these patients are the exceptions to the rule. In the vast majority of cases, carefully
considered titration of medication can result in a satisfactory outcome, one that ablates the patient's
pain and maintains his dignity and comfort.
Howard L. Rosner, M.D., is Associate Professor of Clinical Anesthesiology at Cornell University Medical College and Director of Pain Management Service at The New York Hospital.