Page 1658 - Hematology_ Basic Principles and Practice ( PDFDrive )

1476 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

WHO ANALGESIC LADDER can precipitate bronchospasm in as many as 20%. Significant edema
21
can occur in patients with cirrhosis or congestive heart failure. The
Severe pain relatively selective COX-2 inhibitors, such as meloxicam, celecoxib,
Opioid + nonopioid and nabumetone, have been shown to cause similar gastrointestinal
23
side effects as nonselective NSAIDs. If NSAIDs are required in
± Adjuvant patients with a history of significant gastritis or ulcer disease, or who
are older than 70 years, COX-2 inhibitors or a concomitant proton
Moderate pain
Morphine pump inhibitor should be considered. Cardiotoxicity is well described
24
Opioid + nonopioid Oxycodone in the literature for COX-2 selective inhibitors. Recently, the cardiac
Hydromorphone risk associated with traditional NSAIDs has been questioned. In
± Adjuvant Methadone a metaanalysis that included naproxen, ibuprofen, diclofenac, and
Fentanyl several COX-2–specific inhibitors, ibuprofen and diclofenac dem-
Codeine Ketorolac
Mild pain Hydrocodone Step 3 onstrated an increased risk of stroke. Diclofenac was also associated
Nonopioid Tramadol with an increased risk of cardiovascular death. Naproxen was not
24
Oxycodone* noted to increase risk in this study. Nonopioid analgesics should
± Adjuvant Step 2 be continued when opioid analgesics are added because they can
25
potentiate the pain-relieving effect of the opioid (see Fig. 91.1).
ASA, NSAID However, when aspirin or acetaminophen is included in a fixed drug
Acetaminophen combination (e.g., Percodan, Percocet), toxicities may develop if the
patient uses the medication more frequently than prescribed. The
Step 1 metabolism of salicylates is limited by the capacity of the hepatic
9
Advance up the ladder if pain persists microsomal system. After it is saturated, salicylate levels are depen-
dent on renal clearance. Small increases in maintenance doses can
Fig. 91.1 STRATEGY FOR PHARMACOLOGIC MANAGEMENT OF lead to serious salicylism. Patients with low albumin levels or acid
PAIN USING A MODIFIED (FOUR-STEP) WORLD HEALTH ORGA- urine are particularly susceptible to the development of salicylate
NIZATIONANALGESIC LADDER. Multiagent therapy is usually required toxicity.
for optimal pain management. Patients with mild pain should be started on Tramadol, which both weakly inhibits norepinephrine and sero-
a nonopioid analgesic, and those with moderate pain should be started on a tonin reuptake, and weakly binds to µ-opioid receptors and has
step 2 opioid. Many patients can benefit from the addition of a nonopioid opioid-like side effects, can be used for mild-to-moderate pain. A
to the opioid (e.g., for bone pain) or an adjuvant agent to the opioid (e.g., dose of 100 mg is more effective than 60 mg of codeine. Tapentadol
for neuropathic pain). If this combination does not produce adequate relief (Nucynta) also had both µ-receptor agonism and norepinephrine
or the patient presents with severe pain, step 3 opioids should be begun reuptake inhibition. Studied in moderate-to-severe acute postopera-
initially. Toradol (Ketorolac) is a nonsteroidal antiinflammatory drug tive pain, osteoarthritis, and low back pain, doses of 50–100 mg every
(NSAID) with the pain-relieving potency of a step 3 opioid. Many patients 4–6 hours are comparable to oxycodone 10–15 mg every 4–6 hours
can benefit from the addition of nonopioid analgesics or adjuvants, if indi- with less nausea, vomiting, and constipation.
cated. *Oxycodone in combination with products. It has been suggested that
if opioids with nonopioid analgesics and adjuvants is unsuccessful in provid-
ing relief that an additional “4th step” of interventional/intraspinal delivery Management of Moderate-to-Severe Pain
systems should be initiated. ASA, Aspirin; NSAID, nonsteroidal antiinflam-
20
matory drug; WHO, World Health Organisation. Opioid therapy is the cornerstone of management of patients with
moderate-to-severe pain.
In patients with acute moderate-to-severe pain (i.e., >4/10 on
Management of Mild-to-Moderate Pain VRS), intravenous dosing should be started with the goal of rapid
titration (see, for example, National Comprehensive Cancer Network
26
Nonopioid analgesics should be given to patients with mild-to- [NCCN] guidelines for Adult Cancer Pain). In opioid-naive
1,7
moderate pain. Aspirin and nonsteroidal antiinflammatory drugs patients, morphine 2–5 mg or its equivalent (see box on Relative
(NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, are Potencies of Commonly Used Opioids) should be dosed every 15 min
especially useful as antiinflammatory agents because they decrease (peak effect ~15 min). The patient should be reassessed for analgesic
local prostaglandin release through the inhibition of COX (although effect and side effects. If pain is not relieved, then the dose can be
21
the mechanisms for their analgesic properties are not as clear). increased by 50%–100%; if the pain score decreases to an acceptable
Acetaminophen is an effective analgesic but only a weak antiinflam- level, then the same dose can be continued and given as a standing
matory agent. Daily intake of acetaminophen should not exceed 4 g dose “around the clock.” Alternatively, a patient-controlled analgesia
because of the potential hepatic toxicity (see box on Management of (PCA) can also be used in these situations and can provide the patient
Severe Pain). It is important to prescribe an adequate dose of acet- with significant control over their pain experience. Similarly, the PCA
aminophen or NSAID at regular intervals, switching to another demand dose can be calculated over a 24-hour period to determine
nonopioid analgesic only when maximal doses of the first have the “basal dose” of opioid the patient will need for stable analgesia.
become ineffective. 21 This can be provided as a basal rate on the PCA, or given the clinical
Ketorolac tromethamine (Toradol) is an NSAID of particular situation, as a long-acting formulation equivalent to the amount of
22
value in relieving moderate-to-severe acute pain. A parenteral dose demand doses received. In opioid tolerant patients, a dose equivalent
of 30 mg of ketorolac equals the pain-relieving potency of a parenteral to 10%–20% of the patient’s total 24-hour oral requirement should
dose of 15 mg of morphine, and acute toxicity is minimal if the total be administered as an intravenous bolus (see box on Relative Poten-
daily dose is under 100 mg. Oral ketorolac is considered less potent. cies of Commonly Used Opioids) and titrated, as above, every 15
Ketorolac has all of the side effects of the NSAIDs and is not recom- minutes until pain is controlled and acceptable to the patient. For
mended for use beyond 5 days because of an increased risk of renal example, a patient receiving oxycodone sustained release 60 mg twice
toxicity. If that degree of pain relief is needed chronically, an opioid daily, should be prescribed morphine 5–10 mg intravenously every
agent should be substituted. 15 minutes as needed (oxycodone 120 mg is approximately equiva-
Because NSAIDs can cause renal insufficiency in a significant lent to 180 mg of oral morphine, or 60 mg of intravenous morphine;
number of patients, renal function should be assessed 1–2 weeks after take 10%–20% of this dose). The long-acting opioid should be
initiation of any of these agents. NSAIDs should be used with caution continued or converted to a continuous infusion, or given as a basal
in patients with a history of aspirin allergy or asthma because they rate via a PCA.