Page 1665 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 91 Pain Management and Antiemetic Therapy in Hematologic Disorders 1483

Area postrema Cognitive Other
Neurotransmitters Conditioned response Brain edema or tumor
Drugs Dopamine (e.g., from chemotherapy) Adrenal insufficiency
Digoxin, opioids, Serotonin Memories Migraine (D2)
nicotine, ergot, Norepinephrine Sights, sounds, tastes Pregnancy
general anesthetics Enkephalins Anxiety
chemotherapy GABA Expectations
Metabolic disorders Substance P
Uremia, DKA, Receptors
hypoxemia, Dopamine (D2)
hypercalcemia Serotonin (5-HT3)
Bacterial toxins Muscarinic (M1)
Radiotherapy Histaminic (H1) Emetic center
Neurokinin-1 (NK-1)
Nucleus Emesis
Tractus
Solitarius
Gastrointestinal

Labyrinthine stimuli Glossopharyngeal
Motion sickness Vestibular nuclei Vagal afferents stimulation
Ménière disease Splanchnic nerves Gastroparesis
Tumor Acetylcholine Receptors Gastroenteritis
Infection Histamine (H1) GVHD
Other Histamine 5-HT3 R Gastritis
Vection (visual stimuli) Bowel distention
Postoperative
Serotonin Peritoneal
inflammation
Vascular occlusion
Chemotherapy
Radiotherapy

Fig. 91.2 PATHOPHYSIOLOGY OF NAUSEA AND VOMITING. DKA, Diabetic ketoacidosis;
GABA, γ-aminobutyric acid; GVHD, graft-versus-host-disease; 5-HT3, serotonin; 5-HT3 R, serotonin
receptor.
medication (e.g., opioids). Histamine (H1) and acetylcholine (M1) receiving high-dose cisplatin therapy but has been anecdotally
receptors are present on vestibular afferents. Endogenous or exogenous observed in patients receiving other agents.
blood-borne toxins may activate chemoreceptors in the area postrema
of the floor of the fourth ventricle via dopamine type 2 receptors.
Finally, higher CNS centers may activate or inhibit the vomiting Anticipatory Nausea and Vomiting
center. In addition, there may be direct activation of H1 receptors in
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the meninges secondary to increased intracranial pressure. ANV is believed to be a classic conditioned response. Chemotherapy
The means by which chemotherapy agents induce vomiting are administration (the unconditioned stimulus) results in nausea and
still incompletely understood, but the most likely mechanism is vomiting (the unconditioned response). Clinic sights, smells, and
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believed to include stimulation of the chemoreceptor trigger zone. sounds are the conditioned stimuli. After frequent pairings of che-
Other causes of nausea and vomiting in hematologic patients include motherapy administration and the clinic’s sights, smells, and sounds,
stimulation of the cerebral cortex, gastritis and gastroesophageal the responses (nausea and vomiting) can be triggered in the absence
reflux disease, delayed gastric emptying, radiation enteritis, consti- of any chemotherapy by the clinic’s sights, smells, or sounds, or
pation, esophageal candidiasis, inner ear processes, hypoadrenal- simply by seeing clinic personnel even at a location distant from the
ism, hypercalcemia, changes in taste and smell, and anticipatory site of treatment.
nausea. 9 Patients who are at risk for developing ANV are those who have
Although the sites of emetic action of the chemotherapeutic already experienced posttreatment nausea and vomiting. The risk of
agents have not been identified, blocking agents directed against type developing ANV increases with the increasing frequency, severity, and
3 serotonin receptors (5-HT3 receptors), dopamine (D2) receptors, duration of the symptoms. Other possible predisposing factors
and neurokinin (NK-1) receptors have been effective in inhibiting include susceptibility to motion sickness, awareness of tastes or odors
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chemotherapy-induced nausea and vomiting (CINV). Higher during infusions, younger age, lengthier infusions, greater autonomic
centers in the brain, such as the cortex, are also believed to be involved sensitivity, and general anxiety or emotional distress. 9
in producing anticipatory nausea and vomiting (ANV). Cognitive
therapy, as well as antianxiety and amnesic agents, may provide effec-
tive antiemesis. Acute and Delayed Chemotherapy-Induced
Nausea and Vomiting

PATIENT ASSESSMENT Acute CINV is defined as nausea, vomiting, or both occurring within
24 hours of administration of the agent. Although most drugs
Risk factors for developing CINV include age younger than 60 years, produce emesis 1–2 hours after they are given (in patients who have
female gender, history of motion sickness, and hyperemesis gravi- never before received chemotherapy), the onset of emesis from high-
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darum. Patients who have a history of alcohol intake of more than dose intravenous cyclophosphamide is delayed until 9–18 hours after
five alcoholic drinks per day (>100 g of alcohol) tend to have less treatment, and nausea and vomiting from high total doses of cisplatin
nausea and vomiting. This has been studied carefully in patients can occur 24–72 hours later.