include serotonin, dopamine, and neurokinin 1.

The GI system also plays a large part in the initiation of the

emetic response. The GI tract contains enterochromaffin cells in

the GI mucosa. When these cells are damaged by chemotherapy, radiation, anesthetics, or mechanical irritation, serotonin is

released, which can stimulate the vagal afferents as well as directly

stimulate the VC and NTS. The vomiting center then initiates

the emetic response.

The cerebral cortex and limbic system can stimulate the

emetic center in response to emotional states such as anxiety,

pain, and conditioned responses (anticipatory nausea and vomiting). The neurotransmitters involved in this pathway are less well

understood. Disorders of the vestibular system, such as vertigo

and motion sickness, stimulate the VC through acetylcholine and

histamine release.

DIAGNOSIS

The initial evaluation of the patient with nausea and vomiting

should include the onset of symptoms, the severity and duration of symptoms, hydration status, precipitating factors, current

medical conditions and medications, and food and infectious contacts. The etiology of the nausea and vomiting should be determined, if possible, so that underlying conditions can be treated

specifically. Supportive treatment should be initiated, if needed,

including fluid and electrolyte replacement. If the nausea and

vomiting is mild and self-limited, antiemetic therapy may not be

required. For others, however, the appropriate antiemetic therapy will depend on the patient and the etiology of the nausea

and vomiting.

100 Section 1 General Care

Vagal afferents

Amygdala

5-HT

5-HT3 Receptor

AP and NTS

Central pattern

generator

Vomiting Center

Medulla

Small

intestine

Higher central nervous

system centers

(Chemoreceptor Trigger Zone:

5-HT3, D2 and NK1 receptors)

Vagus nerve

Dorsal vagal complex

Enterochromaffin

cells

CHEMOTHERAPY

FIGURE 6-1 Pathways by which chemotherapeutic agents may produce an emetic response. AP, anterior pituitary; 5-HT, serotonin; 5-HT3,

serotonin type 3 receptor; NTS, nucleus tractus solitarius.

MOTION SICKNESS

Clinical Presentation and Risk Factors

CASE 6-1

QUESTION 1: P.C. is a 27-year-old woman who has no significant medical history, with the exception of moderate

dysmenorrhea and motion sickness associated with travel

by air. Previously, she has taken dimenhydrinate before airplane trips with moderate success. She is engaged to be

married, and she and her fianc ´e have decided on a weeklong

Caribbean cruise for their honeymoon. P.C. is concerned

that she may also develop sea sickness and that dimenhydrinate may not control her symptoms, particularly in the

event of rough weather at sea. Will P.C. be at higher risk for

motion sickness?

The symptoms of motion sickness occur in response to an

unusual perception of real or apparent motion. In these situations, there is sensory conflict about body position or motion

through the visual, vestibular, or body proprioceptors. Acetylcholine is thought to be the primary neurotransmitter involved in

signaling the VC, as is histamine, but to a lesser extent. Adrenergic

stimulation can block this transmission. Symptoms begin with

stomach discomfort and progress to salivation changes, sweating, dizziness, lethargy, retching, and emesis. The risk of motion

sickness is low in children younger than 2 years of age. The risk

is highest in children and adolescents compared with adults, and

higher in women than men. In some individuals, sensitivity to

motion sickness diminishes with time.2 Travel by boat is most

likely to cause symptoms; air, car, and train travel is less likely.3,4

The severity of the motion sickness is highly dependent on the

individual and also varies with the weather and position in the

plane or boat. Because of P.C.’s history and her travel plans, she

is at high risk for recurrence of her motion sickness symptoms.

Nonpharmacologic measures or natural remedies may be useful for reducing motion sickness.2 These include riding in the

middle of the boat or plane where the motion is less dramatic,

lying in a semirecumbent position, fixing the vision on the horizon, avoiding reading, and closing the eyes if below deck or in

the cabin. Many people recommend keeping active on a ship

to “get their sea-legs” faster through habituation. The effectiveness of acupressure at the P6 point of the wrist (about three

fingerbreadths above the wrist) is unclear. A controlled-stimulus

trial compared two brands of wristbands with placebo; neither

band was more effective than placebo in preventing symptoms of

motion sickness.5 Studies of ginger preparations also are equivocal. The action of ginger may be through enhanced gastric

emptying and not on the vestibular system.6,7

Overview of Treatment

CASE 6-1, QUESTION 2: For P.C., what medications are

available to prevent and treat motion sickness symptoms?

Anticholinergic agents and antihistamines that cross the

blood–brain barrier effectively prevent and treat motion

sickness.3,4 In general, these medications are more effective in

preventing than treating established symptoms. 5-HT3 receptor

antagonists and NK1 receptor antagonists have not been shown

to be effective in preventing motion sickness.2,6 Nonsedating antihistamines are not as effective as other antihistamines because

they do not sufficiently cross the blood–brain barrier.2,3 Scopolamine has been well studied for the prevention of motion sickness and is highly effective.2,8 In a controlled trial, scopolamine

was more effective than promethazine and both were more

101Nausea and Vomiting Chapter 6

TABLE 6-1

Medications for Prevention or Treatment of Motion Sickness in Adults

Medication (Trade Name) Dosage Recommended Use Adverse Effects

Scopolamine

(Transderm-Scop)

1.5 mg TOP behind the ear every 3 days.

Apply at least 3 hours (preferably

6–8 hours) before exposure.

Long-term exposure (>6 hours) to

moderate to intense stimulus.

Alternative treatment for shorter or

milder stimulus.

Dry mouth, drowsiness,

blurred vision, confusion,

fatigue, ataxia

Dimenhydrinate

(Dramamine)

50–100 mg PO every 4–6 hours (max

400 mg/day). May be taken PRN or on

scheduled basis if required.

Short- or long-term exposure to mild to

moderate stimulus. Alternative for

intense stimulus.

Drowsiness, dry mouth,

thickening of secretions,

dizziness

Promethazine (Phenergan) 25 mg PO every 4–6 hours. May be taken

PRN or on scheduled basis if required.

25–50 mg IM every 4–6 hours for

established severe symptoms. May be

taken PRN or on scheduled basis if

required.

In combination with dextroamphetamine

for short exposure to intense stimulus.

Alternative for longer or milder

stimulus.

Drowsiness, orthostatic

hypotension, dry mouth

Meclizine (Antivert, Bonine) 12.5–50 mg PO every 6–24 hours. May be

taken PRN or on scheduled basis if

required.

Alternative for mild stimulus or in

combination for moderate to severe

stimulus.

Drowsiness, dry mouth,

thickening of secretions,

dizziness

Dextroamphetamine

(Dexedrine)

5–10 mg PO every 4–6 hours. May be

taken PRN or on scheduled basis if

required.

In combination with promethazine for

short exposure of intense stimulus.

Restlessness, abuse potential,

insomnia, overstimulation,

tachycardia, palpitations,

hypertension

Cyclizine (Marezine) 50 mg PO every 4–6 hours (max 200

mg/day). May be taken PRN or on

scheduled basis if required.

Alternative for mild stimulus situations. Drowsiness, dry mouth,

IM, intramuscular; PO, oral; PRN, as needed; TOP, topically.

Source: Priesol AJ. Motion sickness. Up To Date. http://www.uptodate.com/contents/motion-sickness?source=search result&selectedTitle=1%7E51. Accessed

September 27, 2010; Shupak A, Gordon CR. Motion sickness: advances in pathogenesis, prediction, prevention, and treatment. Aviat Space Environ Med. 2006;77:1213.

effective than placebo, meclizine, or lorazepam.9 Scopolamine

is available as a topical patch, which bypasses the problem of GI

symptoms associated with motion sickness. Table 6-1 describes

medications effective for motion sickness based on the intensity

of the stimulus, adult doses, and potential adverse effects.

Because P.C. is a susceptible individual in a moderate-severe

stimulus situation, prevention with a scopolamine patch applied

behind the ear every 3 days, starting 6 to 8 hours before departure, should be recommended. If she experiences breakthrough

symptoms, dimenhydrinate or promethazine may be useful. She

should be advised about the potential adverse effects of these

agents, which include drowsiness, confusion, and dry mouth.

CHEMOTHERAPY-INDUCED NAUSEA

AND VOMITING

Clinical Presentation and Risk Factors

CASE 6-2

QUESTION 1: M.C., a 54-year-old woman with breast cancer, is in the clinic today to receive her first cycle of

chemotherapy. Her chemotherapy will consist of intravenous (IV) docetaxel 75 mg/m2, carboplatin dosed to

achieve an area under the curve (AUC) of 6 mg/mL/minute.

This will be repeated every 21 days. In addition, she will

receive trastuzumab 4 mg/kg IV for one dose, then 2 mg/

kg/week for 17 weeks. M.C. does not drink alcohol or

smoke. Her only other medical condition is adult-onset diabetes, which is controlled with metformin and diet. She has

had four children, now all grown, and had substantial morning sickness with each of her pregnancies. M.C.’s neighbor

has told her that all chemotherapy causes severe nausea

and vomiting. How likely is M.C. to experience nausea and

vomiting?

Chemotherapy-induced nausea and vomiting (CINV) occurs

in many patients receiving chemotherapy for cancer.1 The mechanisms of the emetic response described at the beginning of

this chapter apply to CINV as well. The major neurotransmitter

receptors involved in these pathways include 5-HT3, NK1, and

dopamine receptors. CINV can occur in different phases. Acutephase CINV symptoms occur within a few hours after the administration of the chemotherapy. These symptoms often peak several hours after administration and can last for the first 24 hours.

Some antineoplastic agents can also cause nausea and vomiting

symptoms for a longer time after chemotherapy administration.

These delayed CINV symptoms peak in about 2 to 3 days and can

last 6 to 7 days. Some patients experience acute symptoms without delayed symptoms. Some other patients experience delayed

symptoms without acute symptoms, and many patients experience CINV in both the acute and delayed phases. Some patients

who have received previous chemotherapy treatments may experience a conditioned response in which they have symptoms even

before the chemotherapy starts. This is called anticipatory nausea

and vomiting, and it is difficult to treat because it is primarily triggered by poor nausea and vomiting control in previous cycles.

Breakthrough nausea and vomiting occur if the primary prophylactic antiemetics fail to work completely. Of course, regardless of

the time course and cause, these are very distressing, unpleasant,

and disruptive symptoms for the patient.

The likelihood of CINV depends on several factors.1 Patientrelated factors that increase the risk of acute-phase CINV include

age younger than 50 years, female sex, poor control of symptoms in prior cycles, history of motion sickness or nausea

with pregnancy, anxiety, or depression. A significant history of

alcoholism actually protects against CINV. Delayed symptoms

are more common in women, in those who have had poor

102 Section 1 General Care

emetic control in the acute phase, and in patients with anxiety or

depression.

Chemotherapy-related factors also predict the likelihood of

symptoms. Factors such as shorter infusion time, higher dose,

and more chemotherapy cycles increase the risk of CINV. With

multiday chemotherapy regimens, the symptoms usually peak

on about the third to fourth day of chemotherapy, when the

acute symptoms caused by the later days’ doses are overlapping

with the delayed symptoms from the first days’ doses. The most

predictive factor, however, is the chemotherapy agent’s inherent

ability to cause CINV, or its emetogenicity.1,10,11 Antineoplastics

that are most likely (>90% of patients) to cause symptoms are

classified as highly emetogenic chemotherapy. Agents that cause

nausea and vomiting in 30% to 90% of patients are classified as

moderate-risk agents. Low emetogenicity agents cause symptoms in 10% to 30% of patients. Other chemotherapy agents

have a minimal risk, causing CINV in less than 10% of patients.

Table 6-2 lists selected chemotherapy agents in the various emetogenicity classes, noting that references differ in the estimation

of emetic risk for some antineoplastic agents. The emetogenicity

risk also depends on the dosage used and the route of administration.

Certain antineoplastic agents are more likely to cause

delayed CINV symptoms. These include cisplatin, carboplatin,

cyclophosphamide, doxorubicin, epirubicin, ifosfamide, and to

a lesser degree, irinotecan and methotrexate. Patients receiving

more than one of these agents are at high risk for delayed symptoms.

Most chemotherapy agents are given in combinations,

rather than as single agents. Estimating the emetogenicity of

chemotherapy combinations has always been difficult. The

chemotherapy regimen that contains cyclophosphamide and

either doxorubicin or epirubicin for breast cancer in females is

highly emetogenic (symptoms in>90% of patients). The primary

literature of the regimen should always be consulted to determine the emetic risk. Should that not be available, the antiemetic

regimen should be geared toward the chemotherapy agent with

the highest emetogenicity level given on that day.1,12,13 For example, in a chemotherapy combination with one high-risk agent

and one with a moderate risk, the antiemetic regimen should be

appropriate for the high-risk chemotherapy agent.

Antiemetic efficacy, or complete emetic response, is usually

defined as no emesis and no nausea or only mild nausea in the

first 24 hours after chemotherapy administration. With currently

recommended antiemetic regimens, most, but not all, patients

will be protected from emesis in the acute phase (first 24 hours).

Nausea, however, is more difficult to control. In addition, delayed

CINV symptoms are more difficult to prevent.

Overview of Treatment

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

CINV. Her personal risk factors include female sex, history of

morning sickness with pregnancy, and being a nondrinker.

The docetaxel has a low risk of acute CINV, the carboplatin

has a moderate risk of acute CINV with a high risk of delayed

CINV, and the trastuzumab has a minimal risk of acute CINV.

What antiemetics are available for M.C.?

Appropriate antiemetic therapy is based on the emetogenicity

of the chemotherapy regimen and patient risk factors. Because

the pathophysiologic response of nausea and vomiting involves

many neurotransmitters, combinations of antiemetics from different therapeutic classes will be more effective in most situations

than a single agent. The predominant classes of antiemetics used

for CINV include 5-HT3 antagonists, the NK1 antagonist, and

corticosteroids.

5-HT3 ANTAGONISTS

The 5-HT3 antagonists inhibit the action of serotonin in the GI

tract and the CNS and thereby block the transmission of emetic

signals to the VC. 5-HT3 antagonists are both highly effective and

have minimal side effects. Several agents and dosage forms in this

class are now available: ondansetron, granisetron, dolasetron, and

palonosetron. Dosages of these agents are shown in Table 6-3.

The route of administration should be matched to the clinical status of the patient. Oral tablets are appropriate for most

patients, but intravenous, topical, or oral dissolving tablet formulations may be needed in patients who cannot take oral medications.

These agents have been widely studied, and some commonalities have emerged. All of the 5-HT3 antagonists are considered

to have equivalent efficacy.14–19 All of these agents have a threshold effect and so a sufficiently large dose must be given to block

the relevant receptors. In addition, the dose-response curve is

relatively flat, such that escalating the dose beyond the threshold dose does not enhance efficacy. When given in appropriate

doses, all of these agents have similar efficacy for acute CINV, with

response rates of 60% to 80%, depending on study design.1,12,14–19

The effectiveness of the 5-HT3 receptor antagonists is enhanced

by the addition of dexamethasone. The response rate increases

by about 15% to 20% in regimens that include dexamethasone

and a 5-HT3 antagonist.17,20 Oral and IV 5-HT3 administration

are equally effective assuming the patient can take oral medications. The side effects of all the 5-HT3 antagonists are similar and fairly mild and include headache, constipation, diarrhea,

and transient elevations of liver function tests. 5-HT3 antagonists

are one component of optimal antiemetic prophylaxis for acute

CINV. They are not more effective than agents from other classes

(notably dexamethasone, aprepitant, or prochlorperazine) for

delayed CINV.17,21–23 5-HT3 antagonists, therefore, are not generally recommended for delayed CINV. The 5-HT3 antagonists

are metabolized by different cytochrome P-450 enzymes, including CYP1A2, CYP2D6 and CYP3A4. Differences in the metabolic

rate of 5-HT3 antagonists attributable to CYP2D6 polymorphisms might account for differences in efficacy among individual

patients.17 However, these differences are not used clinically to

choose initial antiemetic therapy at this time.

Ondansetron, granisetron, and dolasetron have similar pharmacokinetic parameters. Palonosetron, the newest member of

the 5-HT3 antagonist family, is distinguished by a longer elimination half-life than others in its class. Palonosetron was compared

with single doses of 5-HT3 antagonists with shorter half-lives

in various studies. Palonosetron showed equivalent or somewhat superior efficacy, but questions have arisen regarding the

lack of comparable treatment in the control arms.18,24 One

group of researchers described a three-drug combination of

palonosetron, dexamethasone, and aprepitant in a noncomparative, phase II study with moderately emetogenic chemotherapy, and found that the three-drug combination was safe and

effective.25 Whether palonosetron is equivalent or superior

to other 5-HT3 antagonists should be determined by trials

that compare palonosetron with another 5-HT3 antagonist,

with both treatment arms also containing dexamethasone and

aprepitant in the acute and delayed phases. These trials have

yet to be conducted. Currently, palonosetron is substantially

more expensive than the generic forms of the other 5-HT3

antagonists.

Palonosetron is normally administered as a single 0.25-mg IV

or 0.5-mg oral (PO) dose before chemotherapy. With its long

elimination half-life (about 40 hours), palonosetron should be

103Nausea and Vomiting Chapter 6

TABLE 6-2

 L.P. was seen by a psychiatrist. She was scheduled for counseling and prenatal classes. L.P. seemed eager to attend the classes,

and she talked enthusiastically about the baby when family members came to visit. Because of L.P.’s pregnancy, the decision was

87Managing Drug Overdoses and Poisonings Chapter 4

made to continue NAC for a full 72-hour course with the goal

of protecting the fetal liver as much as possible. Six weeks later,

she had a normal delivery of a healthy 6-pound, 1-ounce baby

girl.

SUMMARY

Unfortunately, there is no cookbook method to treat all poisoned

patients. Each exposure is unique: the patients, substances, symptoms, time of exposure, and circumstances differ in each case.

Treatment of the poisoned patient often involves controversy

because solid, evidence-based science to support a given decision is frequently lacking. When challenged with a poisoning

exposure, consult with a poison control center. By calling 1-800-

222-1222, the call will be connected to the poison center where

consultation is available 24 hours a day nationwide.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT10e. Below are the key references

and websites for this chapter, with the corresponding reference number in this chapter found in parentheses after the

reference.

Key References

Boyle JS et al. Management of the critically poisoned patient.

Scand J Trauma Resusc Emerg Med. 2009;17:29. (29)

Bronstein AC et al. 2009 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila). 2010;48:

979. (3)

Chyka PA et al. Position paper: single-dose activated charcoal.

Clin Toxicol (Phila). 2005;43:61. (46)

Committee on Poison Prevention and Control, Board on Health

Promotion and Disease Prevention, Institute of Medicine of the

National Academies. Poison control center activities, personnel,

and quality assurance. Forging a Poison Prevention and Control System. Chapter 5. Washington, DC: The National Academies Press;

2004. (22)

Forsberg S et al. Coma and impaired consciousness in the emergency room: characteristics of poisoning versus other causes.

Emerg Med J. 2009;26:100. (120)

Kociancic T, Reed MD. Acetaminophen intoxication and length

of treatment: how long is long enough. Pharmacotherapy. 2003;23:

1052. (187)

Manoguerra AS et al. Iron ingestion: an evidence-based consensus guideline for out-of-hospital management.Clin Toxicol (Phila).

2005;43:553. (96)

[No authors listed]. Position paper: cathartics [published correction appears in J Toxicol Clin Toxicol. 2004;42:1000]. J Toxicol Clin

Toxicol. 2004;42:243. (47)

[No authors listed]. Position paper: ipecac syrup [published correction appears in J Toxicol Clin Toxicol. 2004;42:1000]. J Toxicol

Clin Toxicol. 2004;42:133. (44)

[No authors listed]. Position paper: whole bowel irrigation [published correction appears in J Toxicol Clin Toxicol.

2004;42:1000; dosage error in article text]. J Toxicol Clin Toxicol.

2004;42:843. (48)

Proudfoot AT et al. Position paper on urine alkalinization.

J Toxicol Clin Toxicol. 2004;42:1. (70)

Rumack BH et al. Acetaminophen overdose: 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med. 1981;

141(3 Spec No):380. (166)

Liebelt EL. Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal

role for alkalinization and sodium loading. Pediatr Emerg Care.

1998;14:293. (150)

Temple AR. Pathophysiology of aspirin overdosage toxicity, with

implications for management. Pediatrics. 1978;62(5 Pt 2 Suppl):

873. (81)

Vale JA et al. Position paper: gastric lavage. J Toxicol Clin Toxicol.

2004;42:933. (45)

Key Websites

CDC Injury Prevention and Control: Data and Statistics.

http://www.cdc.gov/injury/wisqars/index.html.

Drug Abuse Warning Network. https://dawninfo.samhsa.

gov/data.

5 End-of-Life Care

Victoria F. Ferraresi

CORE PRINCIPLES

CHAPTER CASES

1 End-of-life care consists of palliative and hospice care. It is ideally introduced early

in the disease progression to provide support to patients of all ages with a serious

chronic or life-threatening illness. Medicare patients who enter a hospice program

agree to relinquish their regular Medicare benefits as they relate to the terminal

illness, and accept the palliative rather than curative approach that will be provided

by hospice. The hospice provides all care related to the hospice diagnosis under a

managed-care model at a fixed reimbursement.

Case 5-1 (Question 1)

2 In 2008, the Hospice Conditions of Participation were updated to include a review

of the medication profile as part of the initial assessment of new patients. The

medication regimens of hospice patients should be continually reviewed and

updated, with unnecessary, ineffective, or duplicative medications discontinued.

Case 5-1 (Question 2)

3 Patients near end of life can experience a number of distressing symptoms. These

should be anticipated and treated in a timely manner that is acceptable to the

patients and their families.

Case 5-1 (Question 3)

4 Well-trained pharmacists can improve medication management for hospice

patients, while helping the hospice manage their drug costs.

Case 5-1 (Question 2)

5 Many barriers exist regarding pain management and the use of opioids. Case 5-1 (Question 4)

6 Effective pain management uses a variety of approaches. Case 5-2 (Question 1)

7 Pain and symptom management may at times require an aggressive approach. Case 5-3 (Questions 1–3)

HOSPICE AND PALLIATIVE CARE

Terminology

Hospice care and palliative care are similar, but distinct, terms

sharing the common belief that the relief of suffering is a longstanding, central, and fully legitimate aim of medicine. End-of-life

carerefers to both hospice care and palliative care. The basic principle of end-of-life care is to optimize the quality of life for the

patient and family in the last weeks and months of life, as well

as to provide support for the family beyond the end of life into

bereavement.

Palliative care, which includes hospice care, is ideally introduced early in the disease progression to provide support to

patients of all ages with a serious chronic or life-threatening illness. It can be provided concurrently with other treatments to

cure or reduce disease, or it can be provided independently. The

word palliation, derived from the Latin word pallium(a cloak), has

been defined as “treatment to reduce the violence of a disease.”

The World Health Organization and the National Consensus

Project define palliative care as an approach that improves the

quality of life of patients and their families who are facing a lifethreatening illness, by preventing and relieving suffering through

early identification and impeccable assessment and treatment of

pain and other physical, psychosocial, and spiritual problems.1–4

Palliative care:

 Affirms life and regards dying as a normal process

 Provides relief from pain and other distressing symptoms

 Intends neither to hasten nor postpone death

 Integrates the psychological and spiritual aspects of patient

care

 Offers a support system to help patients live as actively as

possible until death

 Uses a multidisciplinary team approach to address the needs

of the patient and his or her family during the patient’s illness

and

 Provides bereavement counseling when indicated.3

88

of up to 120 PCA attempts in 24 hours reflects his continued pain. He describes the intensity of his pain as 8 of

10. Before considering palliative sedation, what other therapeutic interventions can be implemented for D.V.?

Before considering palliative sedation, patients should be thoroughly assessed for insomnia and depression. Underlying reasons

for insomnia should be explored and treated. Poor pain management is often the cause. In D.V., lidocaine 0.5 to 1 mg/kg/hour

administered IV or subcutaneously might be useful to assist in

the management of his severe neuropathic pain.89–93 Lidocaine

purportedly interrupts pain transmission by blocking sodium

channels (see Chapter 7, Pain and Its Management).

D.V. was started on lidocaine 1 mg/kg/hour IV. A bolus

dose was not given because of the short half-life of lidocaine.

Overnight, his use of hydromorphone boluses dropped to one.

He now reports his pain as 1 of 10 and that he slept through the

night for the first time in months. During the next 2 days, the

hydromorphone basal rate was tapered to 5 mg/hour. He did

not experience any lidocaine toxicity, such as perioral numbness,

metallic taste, or somnolence. D.V. continued on lidocaine, using

no hydromorphone boluses for the next 2 weeks, until he died

at home surrounded by his family.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT10e. Below are the key references

and website for this chapter, with the corresponding reference number in this chapter found in parentheses after the

reference.

Key References

Bruera E et al, eds. Textbook of Palliative Medicine. New York, NY:

Oxford University Press; 2006. (2)

National Consensus Project for Quality Palliative Care (2009).

Clinical Practice Guidelines for Quality Palliative Care, Second Edition.

http://www.nationalconsensusproject.org. Accessed March

11, 2011. (4)

Electronic Code of Federal Regulations. Title 42–Public

Health, Chapter IV—Centers for Medicare and Medicaid

Services, Department of Health and Human Services, Part

418—Hospice Care. http://ecfr.gpoaccess.gov/cgi/t/text/

textidx?c=ecfr&sid=6265ddb45c786ea731b66312dcf31d44&

rgn=div5&view=text&node=42:3.0.1.1.5&idno=42. Accessed July 18, 2011. (12)

American Society of Health-System Pharmacists. ASHP statement on the pharmacist’s role in hospice and palliative care. Am

J Health Syst Pharm. 2002;59:1770. (29)

Lycan J et al. Improving efficacy, efficiency and economics of

hospice individualized drug therapy. Am J Hosp Palliat Care.

2002;19:135. (31)

Lee J, McPherson MF. Outcomes of recommendations by hospice

pharmacists. Am J Health Syst Pharm. 2006;63:2235. (33)

Wilson S et al. Impact of pharmacist intervention on clinical

outcomes in the palliative care setting. Am J Hosp Palliat Care.

2010 November 28. [Epub ahead of print] (41)

Victoria Hospice Society. Palliative Performance Scale (PPSv2),

version 2. Medical Care of the Dying. 4th ed. Victoria,

British Columbia, Canada: Victoria Hospice Society; 2006:120.

http://www.victoriahospice.org/sites/default/files/imce/

PPS ENGLISH.pdf. Accessed April 17, 2011. (44)

Qaseem A et al. Evidence-based interventions to improve the

palliative care of pain, dyspnea, and depression at the end of

life: a clinical practice guideline from the American College of

Physicians. Ann Intern Med. 2008;148:141. (56)

U.S. Food and Drug Administration. Code of Federal Regulations Title 21. 21CFR1306.11(g). http://www.accessdata.

fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1306.

11. Accessed April 24, 2011. (69)

Fass J, Fass A. Physician-assisted suicide: ongoing challenges for

pharmacists. Am J Health Syst Pharm. 2011;68:846. (81)

Kirk TW et al. National Hospice and Palliative Care Organization

(NHPCO) position statement and commentary on the use of

palliative sedation in imminently dying terminally ill patients.

J Pain Symptom Manage. 2010;39:914. (83)

Key Websites

American Academy of Hospice and Palliative Medicine

(AAHPM). http://www.aahpm.org/

Center to Advance Palliative Care (CAPC). http://www.capc.

org/

Children’s Hospice and Palliative Care Coalition. http://www.

childrenshospice.org

Centers for Medicare & Medicaid Services (CMS). http://www.

cms.gov/center/hospice.asp

End of Life/Palliative Education Resource Center (EPERC).

http://www.eperc.mcw.edu/eperc

Hospice Foundation of America (HFA). http://www.

hospicefoundation.org/

Innovations in End-of-Life Care (an international journal of leaders in end-of-life care). http://www2.edc.org/lastacts/

International Association for Hospice & Palliative Care (IAHPC).

http://www.hospicecare.com/

MedlinePlus. Hospice Care. http://www.nlm.nih.gov/

medlineplus/hospicecare.html

National Hospice and Palliative Care Organization (NHPCO).

http://www.nhpco.org/

The Population-based Palliative Care Research Network

(PoPCRN). http://www.ucdenver.edu/academics/colleges/

medicalschool/departments/medicine/GIM/Popcrn/Pages/

PopcrnHome.aspx

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M00 overview/intro lrn overv.html

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nhpco.org/pediatrics

American Academy of Pediatrics. Section on Hospice and Palliative Medicine. http://www.aap.org/sections/palliative

The National Consensus Project for Quality Palliative Care.

http://www.nationalconsensusproject.org

6 Nausea and Vomiting

Lisa K. Lohr

CORE PRINCIPLES

CHAPTER CASES

MOTION SICKNESS

1 Motion sickness is caused by discordant information about body position or motion

received from visual, vestibular, or body proprioceptors. Acetylcholine is thought to

be the primary neurotransmitter involved.

Case 6-1 (Question 1)

2 Transdermal scopolamine is recommended for prophylaxis of motion sickness for

moderate to severe stimuli. Dimenhydrinate or promethazine are recommended for

treatment of breakthrough symptoms. The most common adverse effects of these

agents include drowsiness, confusion, and dry mouth.

Case 6-1 (Question 2),

Table 6-1

CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING

1 Nausea and vomiting are initiated by several stimuli, and mediated by several

neurotransmitters in the central nervous system, peripheral nervous system, and

gastrointestinal tract. Because of the multiple neurotransmitter receptors involved,

successful prophylaxis and treatment of chemotherapy-induced nausea and

vomiting will almost always require medications with more than one mechanism of

action.

Case 6-2 (Question 1)

2 The likelihood of nausea and vomiting depends on patient risk factors and most

importantly on the emetogenicity of the chemotherapy agents prescribed. The

antiemetic regimen should be appropriate for the chemotherapy agent with the

highest emetogenicity level.

Case 6-2 (Question 1),

Table 6-2

3 Patients receiving highly emetogenic chemotherapy should receive prophylaxis

with a 5-serotonin receptor type 3 (5-HT3) antagonist, dexamethasone, and

fosaprepitant or aprepitant. Patients receiving moderately emetogenic

chemotherapy should receive prophylaxis with a 5-HT3 antagonist and

dexamethasone (plus fosaprepitant or aprepitant for those chemotherapy agents

posing a high risk of delayed nausea and vomiting).

Case 6-2 (Question 2),

Tables 6-3, 6-4,

Figures 6-2, 6-3

4 For breakthrough symptoms, patients should receive rescue antiemetics with a

different mechanism of action than the prophylactic medications and receive more

aggressive antiemetics before the next cycle of chemotherapy.

Case 6-2 (Question 3),

Tables 6-3, 6-4,

Figures 6-2, 6-3

RADIATION-INDUCED NAUSEA AND VOMITING

1 Radiation can cause nausea and vomiting by the same pathways as chemotherapy.

The risk depends on the area and size of the radiation field as well as the fractional

dose of radiation and whether the patient has had chemotherapy in the past.

Case 6-3 (Question 1),

Table 6-5

2 The recommended prophylaxis for radiation-induced nausea and vomiting includes

a 5-HT3 antagonist with dexamethasone for high-risk patients, and with or without

dexamethasone for patients at moderate risk. Breakthrough symptoms may be

treated with a 5-HT3 antagonist or dopamine antagonist.

Case 6-3 (Question 1),

Table 6-5

continued

98

99Nausea and Vomiting Chapter 6

CHAPTER CASES

POSTOPERATIVE NAUSEA AND VOMITING

1 The risk of postoperative nausea and vomiting depends on several patient, surgical

and anesthetic factors. The antiemetic regimen should be proportional to the risk

factors.

Case 6-4 (Question 1),

Table 6-6

2 The most active agents in preventing postoperative nausea and vomiting are 5-HT3

antagonists. For patients at moderate to high risk, a 5-HT3 antagonist should be

combined with dexamethasone or droperidol. Antiemetics used for rescue therapy

should be of a different class than the prophylaxis agents used.

Case 6-4 (Question 1),

Table 6-6

DEFINITION

Nausea and vomiting are unpleasant symptoms caused by selflimiting disorders or serious conditions such as cancer. These

symptoms can range from mild, short-lived nausea to continuing severe emesis and retching. The emetic response can be

described in three phases: nausea, vomiting, and retching. Nausea is the subjective feeling of the need to vomit. It includes an

unpleasant sensation in the mouth and stomach and can be associated with salivation, sweating, dizziness, and tachycardia. Vomiting is the forceful expulsion of the stomach contents through

the mouth, but is preceded by the relaxation of the esophageal

sphincter, contraction of the abdominal muscles, and temporary

suspension of breathing. Retching is the rhythmic contraction of

the abdominal muscles without actual emesis. It can accompany

nausea, or occur before or after emesis.

EPIDEMIOLOGY AND CLINICAL

PRESENTATION

Nausea and vomiting are caused by many disorders. Central nervous system (CNS) causes include increased intracranial pressure, migraine headaches, brain metastases, vestibular dysfunction, alcohol intoxication, and anxiety. Infectious disease causes

include viral gastroenteritis, food poisoning, peritonitis, meningitis, and urinary tract infections. Metabolic causes include

hypercalcemia, uremia, hyperglycemia, and hyponatremia. Gastrointestinal disorders, such as gastroparesis, bowel obstruction,

distension, and mechanical irritation, can cause nausea and vomiting. Among the many medications that can cause nausea and

vomiting are cancer chemotherapy, antibiotics, antifungals, and

opiate analgesics.

In addition to the suffering involved, uncontrolled vomiting

can lead to dehydration, electrolyte imbalances, malnutrition,

aspiration pneumonia, and esophageal tears. Nausea and vomiting often reduces food intake and can impair a person’s ability

to care for himself or herself. Significant reductions in qualityof-life scores have been demonstrated in cancer patients with

chemotherapy-induced nausea and vomiting compared with

patients who did not have those symptoms.1

PATHOPHYSIOLOGY

The CNS, the peripheral nervous system, and the gastrointestinal

(GI) tract are all involved in initiating and coordinating the emetic

response. In the CNS, the vomiting center (VC) receives incoming signals from other parts of the brain and the GI tract and then

coordinates the emetic response by sending signals to the effector

organs. The VC is located in the medulla oblongata of the brain,

near the nucleus tractus solitarius (NTS). The VC is stimulated

by neurotransmitters released from the chemoreceptor trigger

zone (CTZ), the GI tract, the cerebral cortex, the limbic system,

and the vestibular system (Fig. 6-1). The major neurotransmitter

receptors associated with the emetic response include serotonin (the 5-hydroxytryptamine type 3, [5-HT3]) receptors, neurokinin 1 (NK1) receptors, and dopamine receptors. Other receptors involved include corticosteroid, acetylcholine, histamine,

cannabinoid, gabaminergic, and opiate receptors. Many of these

receptors are targets for antiemetic therapy.

In the CNS, the CTZ is located in the area postrema on the

floor of the fourth ventricle in the brainstem; it lies outside the

blood–brain barrier. When the CTZ senses toxins and noxious

substances in the blood or cerebrospinal fluid, it triggers the

emetic response by releasing neurotransmitters that travel to

the VC and the NTS. The major neurotransmitter receptors