response to, cannabinoids, side effects and a lack of pronounced

efficacy limit their use in the general population of chemotherapy

patients. These agents are usually reserved for patients who do

not have adequate relief from other rescue medications, such as

phenothiazines, benzodiazepines, or olanzapine.

CASE 6-2, QUESTION 3: M.C. is at moderate risk for acute

nausea and vomiting and at high risk for delayed CINV

symptoms, as a result of her chemotherapy regimen of

docetaxel, carboplatin, and trastuzumab. What would be

the most appropriate antiemetic regimen for M.C.?

The optimal prophylactic antiemetic regimens depend on the

emetic risk of the chemotherapy regimen. Treatment guidelines

have been developed by several groups, including the American

107Nausea and Vomiting Chapter 6

TABLE 6-4

Recommended Antiemetic Regimens for Chemotherapy-Induced Nausea and Vomiting (CINV) by Emetogenicity of

Chemotherapy Regimen

Emetogenicity Potential

Acute-Phase CINV (Doses Should

be Given 30–60 Minutes Before

Chemotherapy) Delayed-Phase CINV Breakthrough CINV

High-risk IV chemotherapy regimens Day 1: single dose 5-HT3 antagonist +

dexamethasone + aprepitant/

fosaprepitant

Dexamethasone days 2–4 +

aprepitant days 2 and 3 (not

needed if fosaprepitant

150-mg dose used)

Two agents for PRN use

Moderate-risk IV chemotherapy regimens

with high risk of delayed CINV

Day 1: single dose 5-HT3 antagonist +

dexamethasone + aprepitant/

fosaprepitant

Dexamethasone days 2 and 3 +

aprepitant days 2 and 3a

Two agents for PRN use

Other moderate-risk IV chemotherapy

regimens

Day 1: single dose 5-HT3 antagonist +

dexamethasone

None One agent for PRN use

Low-risk IV chemotherapy regimens Single dose dexamethasone or

metoclopramide or prochlorperazine

None Either none or one agent

for PRN use

Minimal-risk IV chemotherapy regimens None None Usually none

High-moderate risk PO chemotherapy

regimens

5-HT3 antagonist None One agent for PRN use

Low-risk PO chemotherapy regimens None None One agent for PRN use

aNCCN guidelines also include as options dexamethasone alone days 2 and 3 or ondansetron/granisetron/dolasetron days 2 and 3 of chemotherapy.

5-HT3, serotonin; CINV, chemotherapy-induced nausea and vomiting; PRN, as needed.

Source: Ettinger DS et al. Antiemesis: clinical practice guidelines in oncology. V2.2010. http://www.nccn.org/professionals/physician gls/pdf/antiemesis.pdf.

Accessed September 30, 2010; American Society of Clinical Oncology et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006

[published correction appears in J Clin Oncol. 2006;24:5341]. J Clin Oncol. 2006;24:2932; Roila F et al. Guideline update for MASCC and ESMO in the prevention of

chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(Suppl 5):v232.

Society of Clinical Oncology (ASCO; http://jco.ascopubs.org/

content/24/18/2932.full.pdf+html)

12; the National Comprehensive Cancer Network (NCCN; http://www.nccn.org/

professionals/physician gls/PDF/antiemesis.pdf; guidelines

can be accessed by creating a free login)1; and the Multinational

Association of Supportive Care in Cancer (MASCC; http://

annonc.oxfordjournals.org.floyd.lib.umn.edu/content/21/

suppl 5/v232.full.pdf+html).13 These evidence- and consensus-based guidelines, which are similar in regard to the roles

of the various antiemetics, are summarized in Table 6-4 and

Figure 6-2.

For M.C., the best regimen would include a single dose of

a 5-HT3 antagonist plus dexamethasone 8 to 12 mg oral or IV

plus oral aprepitant 125 mg on day 1, then oral dexamethasone

8 mg on days 2 through 4 and oral aprepitant 80 mg on days 2

and 3. She should be offered medications for breakthrough CINV

symptoms, such as prochlorperazine and lorazepam. She should

be warned of the potential adverse effects of dexamethasone,

especially hyperglycemia, and counseled to check her blood sugars more frequently and contact her physician if they remain

elevated. M.C. should be advised to maintain a record of her

symptoms and contact her physician if the breakthrough medications are not working or if she cannot keep fluids down.

If M.C. had been prescribed a multiday chemotherapy regimen, prophylaxis with a 5-HT3 antagonist and dexamethasone

should be offered for each day that moderately or highly emetogenic chemotherapy is administered.1,12,13,44 Aprepitant might

be useful with multiday chemotherapy regimens, although it

has not been studied in this context. Preliminary studies indicated that aprepitant was safe to administer for a total of 5 days,

but it is not clear whether the additional doses would increase

the antiemetic effects. If multiday chemotherapy regimens have

a high risk of delayed symptoms, then some therapy (e.g., dexamethasone plus prochlorperazine or metoclopramide, if aprepitant was already administered) for the delayed symptoms should

be continued for at least 2 to 3 days after the last chemotherapy

administration.

Modern antiemetic regimens achieve complete emetic control in about 70% to 90% of patients, but the response rate is

lower for delayed CINV symptoms. If CINV symptoms are not

adequately controlled, alterations in the prophylactic antiemetic

regimen should be made for the next cycle (Fig. 6-3). Suggestions include upgrading to the next higher emetogenicity level

recommendation, adding aprepitant if not already given, and

scheduling antiemetic agents from other pharmacologic classes.

For additional patient cases covering more

CINV situations, go to http://thepoint.

lww.com/AT10e.

Many patients may benefit from nondrug therapy for CINV

symptoms, especially for anticipatory nausea and vomiting and

anxiety. Techniques include guided imagery, hypnosis, relaxation

techniques, systematic desensitization, and music therapy.45

Acupuncture and acupressure techniques have been investigated

for use in CINV, and some patients benefit from their use. The use

of acupressure devices that stimulate the P6 point on the wrist

have been proposed; however, in a controlled trial in patients with

breast cancer, it was not found to be helpful.46 If patients are troubled by CINV symptoms, it is recommended that they refrain

from heavy meals for 8 to 12 hours before the chemotherapy.

They should also avoid heavy, greasy foods and food with strong

aromas. Chewing gum can mask the metallic taste that some

patients perceive. Dry, salty foods can also help settle the stomach.

RADIATION-INDUCED NAUSEA

AND VOMITING

Clinical Presentation and Risk Factors

CASE 6-3

QUESTION 1: E.G. is a 54-year-old man with newly diagnosed head and neck cancer who will receive radiation therapy concurrently with chemotherapy containing cisplatin

and fluorouracil. His daily (Monday through Friday) radiation

108 Section 1 General Care

Monitor patient for efficacy and toxicity

Minimal or no breakthrough

symptoms; no toxicity

No change in therapy

More than minimal breakthrough

symptoms

Schedule PRN medications, add

other PRN medications, consider

need for IV hydration or electrolyte

supplementation

Adverse effects from antiemetics

 Reduce dose for

drowsiness/confusion, offer pain

medication for headaches, offer

hypnotic agents for insomnia,

monitor glucose and give insulin

for hyperglycemia

Minimal emetogenicity

chemotherapy

Low emetogenicity

chemotherapy

Moderately emetogenic

chemotherapy without a

high risk of delayed

CINV

Moderately emetogenic

chemotherapy with risk

of delayed CINV

Highly emetogenic

chemotherapy

Acute phase:

none

Acute phase:

prochlorperazine or

metoclopramide or

dexamethasone or

Acute phase: singledose 5-HT3-RA +

dexamethasone

Acute phase:

single-dose 5-HT3-RA +

dexamethasone +

fosaprepitant/aprepitant

Acute phase:

single-dose 5-HT3-RA +

dexamethasone +

fosaprepitant/aprepitant

Delayed phase:

none

Delayed phase:

none

Delayed phase:

none

Delayed phase:

dexamethasone D2-3 +

aprepitant D2-3

Delayed phase:

dexamethasone D2-4 +

aprepitant D2-3 (not

if fosaprepitant 150 mg

used )

Possibly one PRN

medication

Provide one PRN

medication

Provide one PRN

medication

Provide two PRN

medications

Provide two PRN

medications

Determine the highest emetogenicity

of the chemotherapy given on each day

Consider patient risk factors

Patient receiving first cycle of chemotherapy

FIGURE 6-2 Algorithm for antiemetic selection for an initial chemotherapy cycle. CINV, chemotherapy-induced nausea and vomiting; D,

days; 5-HT3-RA, serotonin type 3 receptor antagonist; PRN, as needed.

treatments will last for 6 weeks. He has a heavy smoking

history (35 pack-years) and “quit” last week, although it

is not going well. After E.G.’s nausea and vomiting from

the chemotherapy subsides, is he at risk for experiencing

radiation-induced nausea and vomiting? What antiemetic

prophylaxis is appropriate?

Radiation therapy can cause nausea and vomiting through

the same basic pathways that chemotherapy does. Radiationinduced nausea and vomiting (RINV) affects 40% to 80% of

patients receiving radiation therapy. The risk of RINV depends

on several factors, namely the size and area to be irradiated,

larger fractional doses of radiation, and whether the patient has

had previous chemotherapy.1,47,48 Patients with radiation areas

larger than 400 cm2 are more likely to have significant RINV

symptoms. The radiation therapy oncologist will determine the

size of the radiation field and fractional doses of radiation to

maximize the efficacy of the radiation therapy. The high dose

used in total body irradiation (associated with hematopoietic

stem cell transplantation) causes RINV in greater than 90% of

patients. Patients receiving radiation to the upper abdominal area

experience nausea and vomiting about 50% to 80% of the time.

Radiation to other areas of the body is less likely to cause nausea

and vomiting. E.G. is at low risk for experiencing RINV because

his radiation site will be in the head and neck region, his radiation site is not likely to be larger than 400 cm2, and he will likely

receive a smaller fractional dose, although he will be receiving

concurrent chemotherapy.

Overview of Treatment

Just as with CINV, symptoms caused by radiation can be

prevented with 5-HT3 antagonists, corticosteroids, or both.

109Nausea and Vomiting Chapter 6

Assess for adverse effects from antiemetics

Adverse effects from antiemetics:

reduce dose, offer pain medication

for headaches, offer hypnotic

agents for insomnia, monitor

glucose, and give insulin for

hyperglycemia

Consider efficacy of last cycle

Anticipatory nausea and vomiting

Offer therapy with a

benzodiazepine; offer behavioral

therapies such as hypnosis or

relaxation techniques

Therapeutic success

Repeat last regimen

Not a therapeutic success

Did patient get an appropriate

prophylaxis regimen?

Schedule around-theclock agents that were

previously given PRN,

add olanzapine

or cannabinoids;

upgrade to next

emetogenicity level

Use appropriate

regimen for next cycle

No Yes

FIGURE 6-3 Algorithm for selection of antiemetic regimens for subsequent chemotherapy cycles. PRN, as needed.

Evidence- and consensus-based recommendations have been

published by several multidisciplinary groups and are shown

in Table 6-5. High-risk RINV is best treated with a combination of a 5-HT3 antagonist and a corticosteroid.1,47–51

Patients receiving concomitant chemotherapy and radiation

should receive antiemetics appropriate for the chemotherapy

regimen.1 Patients receiving radiotherapy in the moderate RINV

risk group can receive either prophylaxis or rescue therapy with

a 5-HT3 antagonist. Because E.G. is at low risk for having RINV

symptoms, he does not need prophylaxis with a 5-HT3 antagonist. If he experiences symptoms, rescue therapy with a dopamine antagonist or a serotonin antagonist should be

offered.

POSTOPERATIVE NAUSEA AND

VOMITING

Clinical Presentation and Risk Factors

CASE 6-4

QUESTION 1: E.W. is a 48-year-old woman who is scheduled

for a laparoscopic cholecystectomy. The scheduled duration of her surgery is less than an hour. Her medical history includes hypertension. She does not have a history of

motion sickness, and she is a nonsmoker. E.W. has never

had surgery before. Her sister-in-law had severe nausea and

vomiting after an outpatient surgical procedure last year,

and E.W. is worried that it might happen to her. What is

E.W.’s risk of having postoperative nausea and vomiting?

What can be done to reduce her risk, and how can symptoms be treated if they occur?

Postoperative nausea and vomiting (PONV) is a common

complication of surgery, affecting 25% to 30% of all patients, but

up to 80% of patients in high-risk groups.52 In surgical patients,

PONV can lead to hospitalizations, stress on the surgical closure,

hematomas, and aspiration pneumonitis. Patient-related, surgical, and anesthetic factors can increase the risk of PONV.52–56

Patient risk factors include female sex, history of motion sickness, nonsmoking status, obesity, and a history of PONV. Some

surgical risk factors for PONV include long duration of surgery

and type of surgical procedure (e.g., laparoscopy, ear-nose-throat

procedures, gynecologic surgeries, and strabismus repair). Anesthetic risk factors include the use of volatile anesthetics or nitrous

oxide (as opposed to IV propofol) and the use of intraoperative or

postoperative opioids. Children are twice as likely to have PONV

as adults.53,57 The risk increases with the child’s age but declines

after puberty.

110 Section 1 General Care

TABLE 6-5

Prophylaxis for Radiation-Induced Nausea and Vomiting

(RINV) for Adults

Emetic Risk Radiation Area Recommendation

High risk Total body irradiation Prophylaxis with a 5-HT3

antagonist (e.g.,

ondansetron 8 mg PO

BID–TID or

granisetron 2 mg PO

daily + dexamethasone

(2 mg PO TID)

Moderate risk Upper abdomen Prophylaxis with a 5-HT3

antagonist (e.g.,

ondansetron 8 mg PO

BID or granisetron

2 mg PO daily) ±

dexamethasone 4 mg

PO daily

Low risk Lower thorax, pelvis,

cranium, craniospinal

region, head/neck

Prophylaxis or rescue with

a 5-HT3 antagonist

Minimal risk Extremities, breast Rescue with a dopamine

antagonist or a 5-HT3

antagonist

Source: Ettinger DS et al. Antiemesis: clinical practice guidelines in oncology.

V2.2010. http://www.nccn.org/professionals/physician gls/pdf/

antiemesis.pdf. Accessed September 30, 2010; Grunberg SM et al. Evaluation of

new antiemetic agents and definition of antineoplastic agent emetogenicity—an

update. Support Care Cancer. 2005;13:80; Roila F et al. Guideline update for

MASCC and ESMO in the prevention of chemotherapy- and radiotherapyinduced nausea and vomiting: results of the Perugia consensus conference. Ann

Oncol. 2010;21(Suppl 5):v232; Feyer P et al. Radiotherapy-induced nausea and

vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy:

update 2009. Support Care Cancer. 2010 Aug 10 [Epub ahead of print]; Abdelsayed

GG. Management of radiation-induced nausea and vomiting. Exp Hematol.

2007;35(4 Suppl 1):34; Urba S. Radiation-induced nausea and vomiting. J Natl

Compr Canc Netw. 2007;5:60.

Certain anesthesia practices may reduce the risk of PONV.

These include use of regional anesthesia (instead of general

anesthesia), use of total IV anesthesia with propofol, use of

intraoperative oxygen, adequate hydration, and avoidance of

nitrous oxide, volatile anesthesia therapy, and intraoperative or

postoperative opiates.52–54,56–58

Several risk factor models have been studied to correlate these

factors into recommendations for prevention and therapy.52,54

One model is both simple and practical, and uses the following

risk factors: female sex, history of PONV or motion sickness,

nonsmoking status, surgery longer than 60 minutes in duration,

and the use of intraoperative opioids. If the patient has zero or

one risk factor, the risk of PONV is about 10% to 20%, and no

prophylaxis is necessary unless there is a medical risk for emesis.

If the patient has two or more risk factors, the incidence increases

to 40% to 80%, and prophylaxis with one or two medications is

warranted. E.W. has at least two risk factors (female, nonsmoker)

and may have more if her surgery lasts longer than expected or

if she receives intraoperative or postoperative opioids. She has a

moderate to high risk of PONV.

Overview of Treatment

An optimal prophylactic regimen for PONV matches medication choice with the patient’s risk level.52–54,56,57,59 Patients

with zero or one risk factor usually will not need any prophylaxis. Patients with moderate risk (two to three risk factors)

should receive one to two antiemetics. Appropriate choices for

monotherapy include droperidol, a 5-HT3 antagonist, or dexamethasone. Patients at the highest risk for PONV (at least four

risk factors) should be given prophylaxis with a combination of

two to three antiemetics. Dual-therapy choices include a 5-HT3

antagonist plus either droperidol or dexamethasone. Triple therapy would combine a 5-HT3 antagonist plus dexamethasone

plus droperidol. Because E.W. has a moderate to high risk for

PONV, a combination of a 5-HT3 antagonist (such as ondansetron

4–8 mg at the end of surgery) and dexamethasone (4–8 mg at the

start of anesthesia induction) would be a good choice for prophylactic therapy.

The most effective and commonly used medications