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1482 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

TABLE Classification of Transplant-Related Pain Syndromes calcium and magnesium infusions should not be utilized in the
91.3 prevention of CIPN. Chemoprotectants have also not withstood
Deep somatic pain Bone marrow expansion and/or sensitization scrutiny; amifostine, nimodipine, and others are not recommended.
Although amitriptyline has not been shown to prevent CIPN, carba-
related to the engraftment, pneumonia, mazepine, oxcarbazepine, and venlafaxine have shown promise,
pleuritic, deep abscess although further evaluation is warranted.
Superficial somatic Oral ulcers and skin lesions associated with Treatment of chemotherapy-induced painful peripheral neuropa-
pain acute and chronic GVHD; superficial abscess, thy includes the usual agents used for patients with neuropathic pain
ocular lesions associated with chronic GVHD from any etiology (i.e., anticonvulsants, TCAs, and occasionally
Visceral pain Gastrointestinal GVHD, neutropenic enterocolitis, tramadol or opioids). Duloxetine, a serotonin and norepinephrine
visceral involvement by HZV and CMV reuptake inhibitor (SNRI), has been shown to improve CIPN at a
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dose of 60 mg daily. In addition to treating these painful symptoms
Neuropathic pain HZV outbreak and PHN
of neuropathy, the doses of the chemotherapy often require reduction
CMV, Cytomegalovirus; GVHD, graft-versus-host disease; HZV, herpes zoster or even discontinuation of therapy.
virus; PHN, postherpetic neuralgia.
Courtesy Niscola P et al: Pain syndromes in the setting of haematopoietic stem
cell transplantation for haematological malignancies. Bone Marrow Transplant
41:757, 2008; doi:10.1038/bmt.2008.3. Problems in Elderly Patients
Pain management in elderly patients is a highly prevalent problem.
It is complicated by difficulties in pain assessment and by the altered
pharmacokinetics of opioids and of psychotropic adjuvant medica-
patients is thought to be secondary to sickle cell disease injury prior tions. Elderly patients may underreport pain because of misconcep-
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to SCT. 65 tions that pain is part of the aging process or fears of addiction.
Physicians may ascribe observed limitations in social contacts and
physical activities to age-related changes when they are pain-induced
Graft-Versus-Host Disease limitations.
Elderly patients are particularly susceptible to the side effects of
For patients who have undergone bone marrow transplantation, NSAIDs and opioids, and patients taking them should be monitored
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GVHD can be a significant problem. The usual triad of GVHD closely. In elderly patients (70–89 years old), the volume of distribu-
includes hepatitis, dermatitis, and gastroenteritis. Patients are usually tion for opioids is generally smaller, the drugs have longer plasma
unable to take oral, rectal, subcutaneous, or transdermal opioids half-lives, and renal and hepatic clearances are decreased, all of which
because of the effects on the skin (GVHD), lining of the gastro- can prolong the duration of effect. The effective doses for these
intestinal tract (mucositis, infection, and GVHD), and thrombocy- patients are half to one-fourth of those needed in younger patients.
topenia. Polyarthritis and musculoskeletal manifestations can cause Drugs with short half-lives (e.g., morphine, oxycodone, hydromor-
significant pain (Table 91.3). Therefore pain management with phone) should be used, and initial doses should be low. Patients
intravenous opioids is a necessity. The intestinal involvement that should be monitored carefully for the development of sedation or
usually causes the most physical pain includes abdominal cramping confusion, especially if they are receiving antihistaminic agents (e.g.,
and voluminous diarrhea. Treatment often begins with intravenous famotidine, diphenhydramine), drugs with anticholinergic activity,
opioids given through a PCA pump. Addition of octreotide continu- or hypnotics.
ous infusion at 50–100 µg/hour intravenously or intermittent dosing Neuropathic pain syndromes are common in older adults, and the
at 500 µg subcutaneously every 8 hours may be effective in decreas- adjuvant analgesics gabapentin and pregabalin are often used.
ing the volume of diarrhea and level of abdominal pain. 9 Common side effects include somnolence, dizziness, fatigue, and
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weight changes that can be problematic in the geriatric population.
Peripheral Neuropathy Caused by Treatment should be initiated at 100 mg of gabapentin or 50 mg of
pregabalin at bedtime, and close monitoring for side effects should
Chemotherapy Agents occur before dose escalation. Acute urinary retention caused by
opioids (especially in patients with prostatic hypertrophy) and the
Several chemotherapy agents used in the treatment of hematologic hypotension and tachycardia caused by tricyclic compounds can
malignancies can cause painful sensory peripheral neuropathy. The occur more frequently and be more clinically severe in this popula-
vinca alkaloids, most notably vincristine, are neurotoxic, but they are tion. The starting dose of nortriptyline should be low (usually 10 mg
not always associated with painful neuropathy. Thalidomide, at bedtime), and the dose should be slowly increased as tolerated.
lenalidomide, pomalidomide, bortezomib, carfilzomib, cisplatin, Treatment of opioid-related urinary retention may include generic
oxaliplatin, and paclitaxel are all commonly used agents that carry a Proscar (5 mg/day) in patients with benign prostatic hypertrophy and
significant risk of causing painful peripheral neuropathy. The most bethanechol (10–50 mg three times daily) to help increase bladder
common mechanism of neuropathy is damage to the axons starting smooth muscle tone.
with the most distal branches and is a result of chemotherapy’s ability
to damage DNA replication, leading to apoptosis. The major mani-
festations are burning paresthesias of the hands and feet, and loss of PATHOPHYSIOLOGY OF NAUSEA AND VOMITING
reflexes. Paclitaxel also causes a motor neuropathy, which predomi-
nately affects proximal muscles. Nausea is the subjective sensation that precedes vomiting. It is caused
Studies have evaluated numerous agents for prevention of painful by stimulation of one or more of four sites—the gastrointestinal tract,
peripheral neuropathy, although there have not been any magic the vestibular system, the chemoreceptor trigger zone in the area
bullets. Most of the research has focused on taxane and platinum- postrema of the floor of the fourth ventricle, or higher centers in the
based chemotherapy agents. The American Society of Clinical Oncol- CNS (Fig. 91.2). The gastrointestinal tract can activate the vomiting
ogy (ASCO) has published a review of the available literature for center by stimulation of mechanoreceptors or chemoreceptors on
prevention and treatment of chemotherapy-induced peripheral neu- glossopharyngeal or vagal afferents (cranial nerves IX and X), or by
ropathy (CIPN). Many vitamins and dietary supplements have been release of serotonin from gut enterochromaffin cells, which in turn
studied; however, most have not consistently shown benefit in larger stimulates serotonin (5-HT3) receptors on vagal afferents. The ves-
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randomized trials. Specifically, the ASCO review indicates that tibular system activates the vomiting center when stimulated by
acetyl-L-carnitine, vitamin E, all-trans retinoic acid, glutathione, and motion or disease (e.g., labyrinthitis) or when sensitized by