Side effects are among the most common reasons cited for failure of
opioids to relieve pain. If side effects are not anticipated and treated
prophylactically patients may avoid taking them or complain that they are
allergic to them. In reality, true allergy to any of the opioids are
rare. Greater compliance with opioid therapy is likely to be achieved if
patients are taught to expect that most of the side effects are either
preventable or manageable.
1. Constipation is the most annoying side effect as far as the patient is
concerned and may defeat the oral administration of opioids if not
effectively treated. Unfortunately, tolerance does not develop to this
pharmacological action of opioids, i.e., with chronic administration of
opioids, normal bowel function does not resume. The nausea and vomiting
sometimes seen with opioid administration is most often related to
constipation; however, other causes must be considered. When correction of
the constipation abolishes the nausea and vomiting, the patient can then
take the opioid orally without problems.
Constipation is best treated prophylactically at the initiation of opioid
therapy. General measures such as exercise, adequate fluid intake, eating
bulk-containing foods (unprocessed bran and bran-containing cereals), and
taking natural colon stimulants such as prune juice should be encouraged,
but these are not often sufficient. The most common approach is to use a
combined senna laxative and stool softener (commercially available without
a prescription as Senokot-S). The effective dose is usually 2 to 4 tablets
twice a day. The actual dose is highly individualized and is not related
to patient weight or amount of opioid taken. The patient should be
instructed to titrate the dose up or down as needed to maintain regular,
comfortable bowel movements at least every other day. Some patients may
require as much as 4 tablets three times a day. If satisfactory results
are not achieved, lactulose or sorbitol, 30 ml once or twice daily can be
added.
It is important to assess the patientıs bowel status before initiating an
opioid or increasing the dose. If the patient is already constipated and
has not had a bowel movement in more than three days, then it is essential
to take action to clean out the bowel. Several doses of lactulose may
achieve the desired result, but in more severe situations (especially if
the patient is already experiencing nausea and/or vomiting) cleansing
enemas are required. One of the more effective enemas is the old
fashioned milk and molasses enema (see recipe in Table V). This is a
small volume enema that is well tolerated and potent in action when
administered as high in the colon as the catheter tip can be inserted
without meeting resistance. For this purpose an enema administration set
with a soft, flexible catheter at least 8 inches long is needed.
Occasionally even an aggressive clean out and prophylaxis with a
laxative/stool softener combination is insufficient. For these refractory
situations a prokinetic agent such as metocopromide (Reglan) or cisapride
(propulsid) can be added.
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Table V: Milk and Molasses Enema Instructions 8 oz warm water 3 oz powdered milk 4.5 oz molasses
Put water and powdered milk into a jar. Close the jar and shake until the
water and milk appear to be fully mixed. Add molasses and shake the
jar again until the mixture appears to have an even color throughout.
Pour the mixture into the enema bag.
Using an enema bag with a long, soft tube (e.g., red rubber catheter)
attached, gently introduce the tube about 12 inches, but do not push
beyond resistance. Administer the enema high. Repeat every 6 hours
until good results are achieved.
Reference: Bisanz, A. (1997) Managing bowel elimination problems in patients with cancer. Oncology Nursing Forum 24(4)679-686. |
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2. Nausea may occur with or without vomiting. Tolerance usually develops
to nausea after several days of opioid therapy. Vomiting accompanies
nausea more often when constipation is not well-controlled. Any complaint
of nausea or vomiting warrants a thorough bowel assessment and
intervention as described. To control the symptom while the patient is
titrating the bowel regimen or developing tolerance antiemetic therapy
with prochlorperazine (Compazine), metoclopramide hydrochloride (Reglan),
lorazepam (Ativan), or haloperidol (Haldol) is often effective. It may be
necessary to use this antiemetic therapy on a scheduled basis for the
first week of opioid therapy, after which it can be discontinued if nausea
disappears or used on an as needed basis.
3. Sedation may occur at the onset of therapy but usually disappears after
a few days. It seems to elicit an overreaction by physicians when it
occurs in their patients and is often the reason cited by the patient for
abandoning the drug. Unfortunately, this often leads to a reduction in
dose to an ineffective level or other treatment modalities are instituted
even though they are less effective. Sedation is also upsetting to family
members; they should be reassured that it is temporary and reversible and
is most often due to pre-existing sleep deprivation. It is not unusual for
the patient to sleep more during the first few days of good pain control.
The patient may complain of feeling drowsy or "drugged." Patients and
families should be cautioned to expect this as the sleep deprivation is
corrected and be reassured that should the problem persist, it can usually
be managed without sacrificing pain control, by reducing the dose
gradually or by changing the opioid.
Occasionally, sedation continues to be a problem, however, it can be
effectively managed with the judicious use of central nervous system
stimulants such as methylphenidate (Ritalin) or dexamphetamine
(Dexedrine). This usual beginning dose is 5 mg upon awakening in the
morning and another dose between noon and 2 PM. Administering the
stimulant later than 2PM may interfere with normal sleep as the drug can
last as long as 6 to 8 hours. The dose should be titrated upward in 5 mg
increments every 2 to 3 days until the desired effect is achieved, or the
patient encounters unwanted side effects. Often the stimulant medication
may enhance the effect of the opioid and the opioid dose can be reduced.
4. Respiratory depression is perhaps the most serious impediment to
adequate pain control with opioids. In particular, inordinate fear of
respiratory depression prevents adequate opioid use resulting in
inadequate pain relief. In considering this side effect, the most
important distinction to be made is whether the patient is tolerant to
opioids or not. The opioid-tolerant patient, i.e., the patient who has
been taking them regularly for several weeks or more, is tolerant to the
respiratory depressant effects and respiratory depression is highly
unlikely, no matter what the dose administered. Also, pain is a natural
antagonist to the respiratory depressant effects of opioids; therefore, as
long as the patient is experiencing pain, there is little likelihood that
respiratory depression will occur. Closer monitoring is warranted in
opioid-naive patients or when another pain intervention, such as an
anesthetic block , effectively takes away the pain stimulus. Care must be
taken in these situations to titrate the opioid dose downward without
precipitating a withdrawal reaction. Withdrawal can be avoided by
administering approximately 1/3 of the previous opioid dose.
Often respiratory depression is attributed to the opioid when in reality,
there is little evidence of respiratory compromise. Although many standard
text books designate a respiratory rate of less than 12 per minute as a
depressed rate, it usually is not. Many sleeping patients who are not
taking opioids will have a respiratory rate of 6-8 per minute and be
perfectly normal. Many factors must be considered in determining whether a
low respiratory rate is detrimental to a patient. For nurses or
paramedical personnel, the "arousable factor" is a satisfactory guide. If
a patient is easily arousable, he or she is unlikely to have significant
respiratory depression. It should be emphasized, however, that significant
respiratory depression is the most serious side effect of opioid therapy
and persistent respiratory rate of < 8 per minute (for 30 minutes or longer
despite stimulation and/or oxygen saturation < 90%, intervention may be
considered).
When true respiratory depression occurs, the quickest method of treatment
is to reproduce the pain the patient is having, i.e., actually stimulate
the pain in the painful area or simply coaching the patient to breathe
deeply. The opioid antagonist naloxone hydrochloride (Narcan) can be
administered judiciously to ultimately correct the situation. One 0.4 mg
ampule of naloxone diluted in 10 ml of normal saline should be slowly
infused intravenously until respirations increase but short of reversing
the analgesia completely. The dose may need to be repeated because
naloxone is a relatively short-acting medication and the duration of
action of the opioid may exceed the effectiveness of naloxone (especially
true for methadone and levorphanol which have longer half-lives). To
maintain analgesia but temporarily prevent recurrent respiratory
depression, it may be necessary to constantly infuse low-dose naloxone
until respiration is stabilized. To do this, add five 0.4 mg ampules of
naloxone to 500 ml of 5% dextrose in water (D5W) to achieve a final
concentration of 0.0004 mg naloxone/ml D5W, and titrate the infusion to
maintain adequate respirations with retention of analgesia. Intense
involvement of the physician is obviously required. Only in critical
situations such as full respiratory arrest, should naloxone be
administered by rapid, direct IV push in an undiluted form. Naloxone is
not a benign drug and can produce serious side effects such as
tachycardia, cardiac irritability, hypertension, and seizures. It can
also produce a severe withdrawal reaction that is not tolerated well by
critically ill or debilitated patients. Sudden and severe reversal of
analgesia by this method is unnecessary and adds greatly to the suffering
experienced by the patient.
5. Myoclonus is a fairly common side effect seen most often with higher
opioid doses. The patient may experience mild to moderate muscle jerks,
most commonly during sleep, but occasionally throughout the day. If the
jerking is mild and not bothersome to the patient, then a simple
explanation that this is a potential side effect should reassure the
patient. If it disrupts sleep or causes exacerbation of the pain
(especially in patients with bone metastases) changing to another opioid
may help. If persistent, or changing to another drug is not desirable,
low doses of a benzodiazepine muscle relaxant may help. Diazepam (Valium)
in doses as low as 2 mg bid or tid, or clonazepam (klonipin) 0.5 mg to 1
mg bid. These drugs may add to sedation, and if the myoclonus is mostly a
problem during sleep, they can be given at bedtime only.
6. Urinary retention occurs infrequently and may also be a transient side
effect. It may be manifested as difficulty in initiating the urine
stream, but can include inability to initiate micturition. Techniques
such as running water, pouring warm water over the perineum, or gentle
bladder massage may be all that is needed. If such simple measures are
not effective then catheterization may be warranted. Intermittent,
straight catheterization is preferred over insertion of a foley
catheter. After several catheterizations the patient may be able to
resume normal voiding. If retention is persistent, try changing to
another opioid or alternative interventions. Only very rarely is it
necessary to teach a patient self-catheterization for continued urinary
retention.
7. Other side effects include confusion, hallucinations, and dizziness.
Like sedation, these are most often temporary. Again, physicians exhibit
an inordinate concern for these effects, and reinforcement of this concern
often comes from the family. The temporary nature of these symptoms should
be emphasized. Tolerance frequently develops to all of them, and patience
is to be encouraged in dealing with them. However, progressive worsening
of these symptoms on stable opioid dosing usually indicates an alternate
cause and should be evaluated.
