PAIN MANAGEMENT IN CHILDREN WITH CANCER

This Booklet was published by the Texas Cancer Council

Copyright 1999

For further booklets or information, contact the Web site: Childcancerpain.org

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AUTHORS:

Marilyn Hockenberry-Eaton, PhD, RN-CS, PNP, CPON, FAAN

Associate Professor of Pediatrics, Baylor College of Medicine Director of Pediatric Nurse Practitioners, Texas Children’s Cancer Center Texas Children’s Hospital, Houston, Texas

Patrick Barrera, BS Project Coordinator

Texas Children’s Cancer Center Texas Children’s Hospital, Houston, Texas Melody Brown, MS, RN, CPON

Coordinator, Children’s Hospice Services The Hospice at the Texas Medical Center, Houston, Texas Sarah J. Bottomley, MN, RN, CPNP, CPON

Pediatric Nurse Practitioner Texas Children’s Cancer Center

Texas Children’s Hospital, Houston, Texas Jill Brace O’Neill, MS, RN-CS, PNP, CPON

Pediatric Nurse Practitioner Texas Children’s Cancer Center Texas Children’s Hospital, Houston, Texas

Texas Children’s Hospital Baylor College of Medicine

REVIEWERS:

Donna Wong, PhD, RN, PNP, CPN, FAAN Nurse Consultant, The Children’s Hospital at Saint Francis, Tulsa Oklahoma; Nurse Consultant, The Hospital for Sick Children, Washington; Adjunct Associate Professor, Department of Pediatrics, University of Oklahoma College of Medicine-Tulsa; Clinical Associate Professor, University of Oklahoma College of Nursing; Adjunct Associate Professor and Consultant, Oral Roberts University, Anna Vaughn School of Nursing, Tulsa, Oklahoma C. Philip Steuber, MD Professor of Pediatrics, Baylor College of Medicine, Houston, Texas Director, Leukemia Service, Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, Texas Douglas Strother, MD Assistant Professor of Pediatrics, Baylor College of Medicine, Houston, Texas Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, Texas Edith M. Eby, PharmD Clinical Pharmacy Specialist, Hematology/Oncology Texas Children’s Hospital, Houston, Texas Nancy E. Kline, PhD, RN, CPNP Assistant Professor of Pediatrics, Baylor College of Medicine Pediatric Oncology Nurse Practitioner Texas Children’s Cancer Center Texas Children’s Hospital, Houston, Texas

ADVISORY COMMITTEE MEMBERS:

Carol Benefield Parent Consultant Candlelighters Childhood Cancer Foundation Alvin, Texas Dana Bond, MN, RN, CPNP Advanced Nurse Practitioner Center for Cancer and Blood Disorders Children’s Medical Center of Dallas Dallas, Texas Marge Brown, RN Driscoll Children’s Hospital, Children’s Medical Center of South TX. Corpus Christi, Texas Melody Brown, MS, RN, CPON Coordinator, Children’s Hospice Services The Hospice at the Texas Medical Center Houston, Texas Margaret Caddy, RN Executive Director, Houston Hospice; President, Texas/New Mexico Hospice Association Houston, Texas

Mary Choroszy, MSN, RN, CPNP Pediatric Nurse Practitioner Pediatric Blood & Marrow Transplantation U.T.M.D. Anderson Cancer Center Houston, Texas John Foster, President Texas Non-Profit Hospice Alliance Bryan, Texas Lanae Juno, RN, OCN Pediatric and Adolescent Oncology Nurse Coordinator Methodist Children’s Hospital Lubbock, Texas Janine Primomo, MSN, RN Department Head Pediatric Hematology Oncology Santa Rosa Children’s Hospital San Antonio, Texas Kathleen M. White, MSN, RN, CPNP Cook Children’s Medical Center Fort Worth, Texas

APON Clinical Practice Committee Reviewers:

Kathy Forte MS, RN, CPNP Clinical Nurse Specialist, AFLAC Cancer Center Egleston Children’s Hospital, Atlanta GA Pat Brophy MSN, RN, CRNP Pediatric Nurse Practitioner Children’s Hospital of Philadelphia, PA Casey Hooke MSN, RN, CPON Clinical Nurse Specialist, Pediatric Hematology/Oncology Children’s Hospitals and Clinics, Minneapolis, MN Susan Lively RN, CPON Oncology Resource nurse Backus Children’s Hospital, Savannah GA Sal Leahy RN Clinical Educator AFLAC Cancer Center Egleston Children’s Hospital, Atlanta GA Gina Mink MS, RN Staff nurse Children’s Hospital, Omaha, NE

Pain Management In Children With Cancer:

Content Outline

Introduction pp 8 I. Physiology of Pain pp 9-10 II. Etiology of Cancer Pain pp 11-13 III. Barriers to Effective Pain Management pp 14-16

IV. Pain Assessment pp 17-23

V. Pharmacologic Pain Management pp 24-44 VI. Procedure Related Pain pp 45-49 VII. Nonpharmacologic Pain Management pp 50-54 VIII. Special Considerations For The Dying Child pp 55-56 IX. Appendices X. References

Note: As new scientific information becomes available through basic and clinical research, recommended treatments and drug therapies undergo changes. The authors and reviewers have made every effort to make the information presented in this booklet up-to-date and accurate in accordance with current standards and research materials available. The authors and reviewers are not responsible for errors or omissions or for any consequences that may result in the application of any of the information presented. Only trained health care providers in accordance with approved professional standards should apply any practice described within this publication. Health care providers are advised to always check product information, before administering any drug, for changes and updates of information regarding dosing and contraindications.

Introduction

Pain in children with cancer is now recognized as a significant debilitating symptom that

affects quality of life. Although advances in pain management have been made, there is still a need

for improvement. Lack of knowledge on state of the art pharmacological and nonpharmacological

practices as well as common myths and misconceptions surrounding opioid use are the most

common barriers to effective pain management. Pain is a significant acute and chronic symptom

during or after treatment and is often undertreated.

This booklet, made possible by the Texas Cancer Council, is written to provide professionals

caring for children with cancer with a resource to improve pain management practices. Better

understanding of the nature of pain, as well as development of new interventions, agents, and

methods of pain medication delivery, are essential to improve care for children. This booklet

provides a broad overview of pain management for children with cancer, with a focus on care for

the terminally ill child.

Many health care professionals caring for children who are terminally ill may be experts in

the care of adults with limited experience in the care of children. Information in this booklet is

presented to allow the clinician access to important information related to the physiology of pain,

etiology of cancer pain in children, assessment of pain, appropriate strategies for pain

management, and effective drugs and dosages for use with children. The ability to reference

information quickly makes this booklet a useful tool in the clinical setting. Management of pain

caused by medical procedures is included, because so many children must undergo procedures

during the course of the illness. Nonpharmacologic pain strategies have been found to be highly

effective in decreasing pain in children and also provide opportunities for family members to

become involved in the care of their child. The final section provides specific information related to

the care of the dying child.

I. Physiology of Pain

Nociceptive Pain:

The sensation of nociceptive pain occurs when the nerve endings in the periphery are

activated by a noxious stimuli. Nociceptive pain generally results as a response to direct tissue

damage. The initial trauma causes the release of several chemicals including bradykinin, serotonin,

substance P, histamine, and prostaglandin. These chemicals facilitate the transmission of the pain

impulse to the spinal cord from the periphery. Small C fibers and large A delta fibers pick up the

messages at the site of injury and transmit the signals to the dorsal horn of the spinal cord.

Neurotransmitters that include glutamate, substance P and adenosine triphosphate allow the pain

message to ascend to the brainstem by the spinothalamic tract and enter the higher centers of the

brain. The cerebrum and thalamus are known as the control centers that process and register the

experience of pain. Once the impulse enters the higher centers of the brain, information about the

pain such as location and intensity is processed as well as other factors that include fear of the

situation, past and present experiences and the child’s current emotional status. All these factors are

considered before a response occurs in an attempt to stop the pain. The brain may respond by

blocking further pain impulses from reaching the higher centers or by producing endogenous

opioids (i.e., endorphins), which saturate pain receptor sites along the spinal cord and in the brain,

providing an analgesic effect.

Neuropathic Pain:

Neuropathic pain is caused by altered excitability of the peripheral or central nervous

system, usually caused by dysfunction or injury. Neuropathic pain is distinguished from

nociceptive pain by its persistence over a longer period of time. Neuropathic pain is frequently

described as a burning, stabbing, or shooting sensation. A complete neurologic exam is essential to

evaluate sensory, motor, cranial nerve, reflex, cerebellar, cognitive and emotional function (Olsson

and Berde, 1993). Sensory evaluation may elicit the presence of hyperalgesia (an increased

sensitivity to pain), or allodynia (pain caused by benign stimuli such as touch). These findings are

significant symptoms associated with neuropathic pain, especially when no apparent skin pathology

is present (Olsson and Berde, 1993). Table 1 describes in more detail the two types of pain found in

children with cancer.

Table 1. Neuropathic versus Nociceptive Pain

Two Major Types of Pain:

I. Nociceptive Pain

II. Neuropathic Pain

A. Somatic Pain B. Visceral Pain C. Centrally Generated Pain

D. Peripherally Generated Pain

I. Nociceptive Pain: Normal process of stimuli that damages normal tissues or has the potential to do so if prolonged; usually responsive to nonopioids and/or opioids.

A. Somatic Pain: Arises from bone, joint, muscle, skin, or connective tissue. It is usually aching or throbbing in quality and is well localized.

B. Visceral Pain: Arises from visceral organs, such as the GI tract and pancreas. This may be subdivided:

1. Tumor involvement of the organ capsule that causes aching and fairly well-localized pain.

2. Obstruction of hollow viscus, which causes intermittent cramping and poorly localized pain.

II. Neuropathic Pain: Abnormal processing of sensory input by the peripheral or central nervous system; treatment usually includes adjuvant analgesics.

A. Centrally Generated Pain

1. Deafferentation pain: Injury to either the peripheral or central nervous system. Examples: Phantom pain may reflect injury to the peripheral nervous system; burning pain below the level of a spinal cord lesion reflects injury to the central nervous system.

2. Sympathetically maintained pain: Associated with dysregulation of the autonomic nervous system. Examples: May include some of the pain associated with reflect sympathetic dystrophy/causalgia (complex regional pain syndrome, type I, type II).

B. Peripherally Generated Pain

1. Painful polyneuropathies: Pain is felt along the distribution of many peripheral nerves. Examples: diabetic neuropathy, alcohol-nutritional neuropathy, and those associated with Guillain-Barré syndrome.

2. Painful mononeuropathies: Usually associated with a known peripheral nerve injury, and pain is felt at least partly along the distribution of the damaged nerve. Examples: nerve root compression, nerve entrapment, trigeminal neuralgia.

A method of classifying pain is inferred pathophysiology: (1) nociceptive pain (stimuli from somatic and visceral structures); (2) neuropathic pain (stimuli abnormally processed by the nervous system).

From Pain: Clinical manual, (p. 19), by M McCaffery and C Pasero, 1999. St. Louis: Mosby. Copyright 1999, Mosby. Reprinted with permission.

II. Etiology of Cancer Pain

Pain in children with cancer can be caused by a number of factors (Table 2). The cancer

mass itself can produce pain by tissue distention or infiltration. Inflammation due to infection,

necrosis, or obstruction can also cause pain. Bone pain in children with cancer is caused by

infiltration of the periosteum, pathologic fractures, tumor growth of surrounding tissues, or

stimulation of the nerve endings in the endosteum by chemical agents released from the diseased

bone. These chemical agents include prostaglandin, bradykinin, substance P and histamine. Bone

marrow infiltration with malignant cells causes pain described as dull, aching, or penetrating, and

can be generalized to one or more areas, or localized. Tissue distention, infiltration or inflammation

may cause a generalized dull, throbbing pain. Visceral organ pain may be poorly localized because

the nociceptors that transmit pain messages back to the brain are not well established. Obstruction

of major organs can cause the onset of acute, severe pain. For example, tumors found in the

retroperitoneum may result in obstruction of a ureter, causing acute onset of sharp, localized pain

that is similar to pain caused by appendicitis. Children with nerve invasion often experience

weakness, numbness, or parasthesias. A child with a spinal cord tumor may complain of muscle

spasms, back pain and heaviness in the lower extremities. These children may also develop urinary

retention or incontinence.

Cancer treatment related pain in children occurs from the three commonly used treatment

modalities: surgery, chemotherapy, and radiation therapy. Children undergoing surgery for excision

of a primary tumor experience postoperative pain and are at risk for secondary infection that may

lead to additional pain. Chemotherapeutic agents can also be a cause of pain during treatment.

Vincristine, a plant alkaloid, is most commonly associated with peripheral neuropathies,

characterized by dysesthetic pain that presents as a burning sensation, causing pain upon light

contact with the skin. Mucositis is a common side effect of chemotherapy, often seen in children

receiving anthracyclines (i.e., daunorubicin), alkylating agents (i.e., cyclophosphamide),

antimetabolites (i.e., methotrexate), and epipodophyllotoxins (i.e., VP-16), and after receiving

preparative regimens for bone marrow transplantation. Radiation therapy to the head and neck area

is associated with severe mucositis in children. Post radiation pain may occur in certain body

regions, caused by fibrosis or scarring of connective tissues and secondary injury to nerve

structures. Other treatment-related side effects that cause pain include: skin reactions from

radiation therapy; abdominal pain from vomiting, diarrhea, or constipation; and infections such as

typhlitis, cellulitis, or sinusitis.

Table 2. Cancer Pain in Children

Type Clinical Presentation Causes Bone -Skull -Vertebrae -Pelvis/femur

-Aching to sharp, severe pain generally more pronounced with movement. Point tenderness common

-skull – headaches, blurred vision -spine – tenderness over spinous process -arms/extremities – pain associated with movement or lifting

-pelvis/femur – associated with movement; pain with weight bearing and walking

-Infiltration of bone -Skeletal metastases - irritation and

stretching of pain receptors in the periosteum and endosteum.

-Prostaglandins released from bone destruction.

Neuropathic -Peripheral -Plexus -Epidural -Cord compression

-Complaints of pain without any detectable tissue damage

-Abnormal or unpleasant sensations, generally described as tingling, burning, or stabbing

-Often a delay in onset -Brief, shooting pain -Increased intensity of pain with receptive stimuli

-Nerve injury caused by tumor infiltration; can also be caused by injury from treatment (i.e., vincristine toxicity).

-Infiltration or compression of peripheral nerves

-Surgical interruption of nerves (phantom pain post amputation).

Visceral -Soft tissue -Tumors of the bowel

-Retroperitoneum

-Poorly localized -Varies in intensity -Pressure, deep or aching

-Obstruction – bowel, urinary tract, biliary tract

-Mucosal ulceration -Metabolic alteration -Nociceptor activation, generally from distention or inflammation of visceral organs

Treatment Related -Mucositis -Infection -Post-LP headaches -Radiation dermatitis

-Post-surgical

-Difficulty swallowing, pain from lesions in the oropharynx. May extend throughout the entire GI tract.

-Infection may be localized pain from a focused infection or generalized (i.e., tissue infection versus septicemia)

-Severe headache following lumbar puncture -Skin inflammation causing redness and breakdown

-Pain related to tissue trauma secondary to surgery

Direct side-effects of treatment for cancer

-Chemotherapy -Radiation -Surgery

III. Barriers To Effective Pain Management

Pain in children is often under treated. The reasons for the lack of adequate pain control

may include: myths about pain and pain management, fears held by parents and health

professionals, and the lack of appropriate pain assessment tools or knowledge of pain assessment.

Myths surrounding pain management may prevent the timely and appropriate treatment of children.

1) Myth: Young infants do not feel pain. Children’s nervous systems are immature and are

unable to perceive and experience pain the way adults do. In the past, procedures such as

circumcision, suturing, or other minor operations on infants have been performed without

the benefit of anesthetic or pain medication. Fact: The central nervous system of a 26-week-

old fetus possesses the anatomical and neurochemical capabilities of experiencing

nociception (Anand, 1998).

2) Myth: Children easily become addicted to narcotics. Fact: Less than 1% of children treated

with opioids develop addiction. Opioids are no more dangerous for children than they are

for adults when appropriately administered (Foley, 1996).

There is confusion regarding three terms associated with drug use; narcotic addiction,

drug tolerance and physical dependency. The following are definitions for these

terms.

• Narcotic addiction - A voluntary psychological behavioral pattern characterized

by drug-seeking behavior and an intense craving for a drug’s mind-altering

properties rather then use for intended medical purposes. Addiction is not a

pharmacological side effect.

• Drug tolerance - An involuntary physiologic adaptation to a drug exhibited by a

need for larger doses of an opioid to maintain the desired analgesic effect.

• Physical dependence - An involuntary physiologic effect of withdrawal

symptoms noted when following abrupt discontinuation of opioids, or

administration of a narcotic antagonist (e.g., naloxone).

3) Myth: Children tolerate pain better than adults. Fact: Younger children experience higher

levels of pain during procedures then older children. Children’s tolerance for pain

increases with age (Broome, Rehwalt and Fogg, 1998; Broome and others 1990).

4) Myth: Children are unable to tell you where they hurt. Fact: Children may not be able to

express their pain in the same manner as adults. However with proper use of pain

assessment scales, children are able to express and identify pain. Studies have shown that

children as young as 3 years of age can use pain scales, such as the faces pain scale,

accurately (Wong and Baker, 1988). Children are able to point to the body area where they

are experiencing pain or draw a picture illustrating their perception of pain.

5) Myth: Children become accustomed to pain or painful procedures. Fact: Children exposed

to repeated painful procedures often experience increasing anxiety and perception of pain

with repeated procedures (Zeltzer, 1990).

6) Myth: Children will tell you when they are experiencing pain. Fact: Children may not

report pain due to fear of administration of a painful analgesic (injection) or fear of

returning to the hospital. Children who have experienced chronic pain may not be aware

that they are experiencing pain. Young children may not have adequate communication

skills or others may not think it is necessary to tell health professionals about the pain

(Favaloro and Touzel, 1990).

7) Myth: Children’s behavior reflects their pain intensity. Fact: Children are unique in their

ways of coping. Children’s behavior is not a specific indication of their pain level (Beyer,

McGrath and Berde, 1990). A child who is experiencing pain may be active and playing

“normally”. For example, a school age child may spend hours with a puzzle rather then

lying in bed as a way to distract attention from pain and attempt to enjoy a favorite activity.

Fears

1) Fear of respiratory depression. Respiratory depression is a serious and well-known side effect

of opioids; however, it rarely occurs in children. Several studies have documented the safe and

effective use of opioids in children without increased risk of respiratory depression (Kart,

Christrup and Rasmussen, 1997; Sabatino and others, 1997; Hertzka and others, 1989). As

children develop a tolerance to the analgesic effect of opioids they often develop a tolerance to

the respiratory depressant effect as well. For this reason, as pain increases, a child should be

able to receive an increased dose of opioids. The most common opioid side effect is

constipation, not respiratory depression. It is important to note that pain acts as a natural

antagonist to the analgesic and the opioid side effects of respiratory depression.

2) Fear of addiction (see myths). The patient or the family may have misconception/fear of

addiction which may lead to reluctance to report pain or take prescribed medications.

3) Fear that pain is a sign that the disease is worsening.

4) Fear that the use of morphine means the child is close to death. In an attempt to avoid facing

that reality, they may not acknowledge pain.

Other Barriers To Adequate Pain Control (Martin, 1998)

1) With a shift towards managed care in an attempt to contain costs, illness/treatment related pain relief may not be viewed as a cost effective treatment modality.

2) There is often a lack of a comprehensive approach to pain assessment.

3) Healthcare providers may underestimate the intensity of the child’s pain.

4) An inadequate dose may be prescribed, or the use of inappropriate medication for symptoms may occur. This may be due to the misunderstanding of the pharmacokinetics of agents and appropriate IV to PO conversions.

5) Health care providers frequently have limited knowledge regarding state of the art pain management.

6) There is often reluctance by nurses or family members to administer medications due to fear of addiction, over medication, and/or side effects.

IV. Pain Assessment

Pain is both a sensory and emotional experience. For this reason several different

assessment strategies are needed to provide qualitative and quantitative information about pain.

Qualitative assessment is a description of the location, duration and characteristics of the pain, as

well as factors affecting the pain. Quantitative assessment evaluates the intensity of the pain using

a pain scale. In the clinical assessment of pain it is essential to ask the patient about his/her pain on

a regular basis and to assess pain systematically. The clinician should believe the patient and/or the

family reports of pain and what treatments they feel are most effective. Empower patients and their

families by involving them in the decision making for pain control. This involvement will ensure

that the pain control option chosen is the most appropriate for the patient, family and setting. It is

important that pain control interventions are delivered in a timely, logical and coordinated fashion

(Jacox and others, 1994). The QUEST approach to pain assessment is comprehensive and promotes

the use of multiple sources to evaluate pain in a child. The following methods are used to assess the

child’s pain.

QUEST PRINCIPLES OF PAIN ASSESSMENT (Baker and Wong, 1987) Question the child. Use pain rating scales. Evaluate behavior and physiologic changes. Secure parents' involvement. Take cause of pain into account. Take action and evaluate results.

Figure 1. Key Factors In The Assessment of A Child In Pain

Pain Assessment

Self Report Physical Examination

Behavioral Observation

Physiologic Measures & Diagnostic Results

1. Self Report

Self report is the most critical component of pain assessment. Children should be

encouraged to describe their pain since their statements reflect the most reliable indicators of pain.

In obtaining the patient's pain history, involve the parents, since they know their child (Table 3).

Know what word the child uses for pain (e.g., hurt, “owie” or “boo-boo”). Specific words used for

“pain” in different languages are found in Appendix A.

Assessment involves both the clinician and the patient and should describe the pain:

• Location (does the pain radiate, is there referred pain) • Intensity/severity • Aggravating and relieving factors • Goals for pain control [document the patient’s preferred assessment tool and goals for pain

control (scores)] • Description of the pain (i.e., sharp, pulsing, dull) • Duration

• Determine associated symptoms and/or side effects the patient may be experiencing in addition

to the pain or discomfort (e.g. nausea, vomiting, constipation, sedation, fatigue).

• Choose an instrument to measure pain, giving consideration to the patient's developmental level;

introduce the instrument prior to painful procedures when possible; use the same instrument

consistently to assess level of pain; know the validity and reliability of pain rating scale chosen

(Figure 1 and Table 4). A self report tool is appropriate for children greater than 3 years of age

and provides the most accurate measure of pain.

• Children experiencing chronic pain need to be assessed for pain at regular intervals to define a

baseline rating for pain.

• Several scales have been developed to aid in measuring pain in nonverbal children (Appendix B

contains references for additional pain assessment scales).

Table 3. Pain Experience History

Child Form Parent Form Tell me what pain is. What word(s) does your child use in regard to pain?

Tell me about the hurt you have had before. Describe the pain experiences your child has had before.

Do you tell others when you hurt? If yes, who? Does your child tell you or others when he/she is hurting?

What do you do for yourself when you are hurting? How do you know when your child is in pain?

What do you want others to do for you when you hurt? How does your child usually react to pain?

What don’t you want others to do for you when you hurt? What do you do for your child when he/she is hurting?

What helps the most to take your hurt away? What does your child do for him/herself when he/she is hurting?

Is there anything special that you want me to know about you when you hurt? (If yes, have child describe.) What works best to decrease or take away your child’s pain?

Is there anything special that you would like me to know about your child and pain? (If yes, describe.)

From Reliability and validity of preverbal pain assessment tools, by BA Joyce, JG Schade, JF Keck, J Gerkensmeyer, T Raftery, S Moser and G Hunter, 1994, Issues Comp Pediatr Nurs 17(3), p 121–135. Copyright 1994 Hemisphere Pub. Corp. Adapted with permission.

Table 4. Pain Rating Scales for Children

Pain Scale Description Recommended Age

FACES Pain Rating Scale ( Whaley and Wong, 1987 with permission; Appendix C, Spanish version of the scale).

Consists of six cartoon faces ranging from a smiling face for “no pain” to tearful face for “worst pain” (numbers for coding may vary).

Children as young as 3 years

0 No Hurt

1 Hurts

Little Bit

2 Hurts

Little More

3 Hurts

Even More

4 Hurts

Whole Lot

5 Hurts Worst

Numeric Scale

Uses straight line with end points identified as

“no pain” and “worst pain”; divisions along line are marked in units from 0 to 5 (high number may vary)

Children as young as 5 years, as long as they can count and have some concept of numbers and their values in relation to other numbers. Scale may be used horizon-tally or vertically.

0 No Pain

1 2 3 4 5 Worst Pain

FACES Scale From Nursing Care of Infants and Children, 3rd ed., (p 1070), by LF Whaley and DL Wong, 1987. St. Louis: Mosby. Copyright 1987, Mosby. Reprinted with permission.

2. Physical Examination

Performing a complete physical examination is vital to a thorough assessment of a patient’s

pain. The physical examination should attempt to establish the relationship of the pain complaint to

the disease. Special attention should be given to the abdomen and gastrointestinal system prior to

initiation of narcotic therapy due to the potential side effect of constipation. Key components to the

complete physical examination include:

General Inspection Head (Eyes, Ears, Nose & Throat) and Neck Chest/Lungs Heart Abdomen Urinary Genitalia & Rectum Musculoskeletal Neurologic Skin

3. Behavioral Observation

Behavioral observation can be used with pre-verbal or nonverbal patients, in addition to self-

report in all other cases. Observations include: vocalizations, verbalizations, facial expressions,

motor responses, body posture, activity and/or appearance (Table 5). Remember pain will be

expressed differently depending on the age and developmental level of the patient (Table 6).

Interpret behaviors cautiously. Behaviors such as watching television, playing or sleeping can

be distraction strategies used for coping with pain.

Cultural background may also play a role in children's reports and responses to pain. It is

accepted that culture is important to consider when assessing a child’s pain; however, little

empirical data exists that compares differences in pain experience and response patterns among

children of various cultures. Clinicians should become familiar with the beliefs and practices

common to the cultural groups they serve, be willing to elicit information about these matters in a

nonjudgmental manner, and accommodate cultural practices in keeping with acceptable medical

practice.

Table 5. Behavioral Pain Assessment Scales For Young Children FLACC Scale

Scoring Categories 0 1 2 Face No particular expression or

smile Occasional grimace or frown, withdrawn, disinterested

Frequent to constant quivering chin, clenched jaw

Legs Normal position or relaxed Uneasy, restless, tense Kicking, or legs drawn up

Activity Lying quietly, normal position, moves easily

Squirming, shifting back and forth, tense

Arched, rigid or jerking

Cry No cry (awake or asleep) Moans or whimpers; occasional complaint

Crying steadily, screams or sobs, frequent complaints

Consolability Content, relaxed Reassured by occasional touching, hugging or being talked to, distractible

Difficult to console or comfort

Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, which results in a total score between zero and ten.

From The FLACC: A behavioral scale for scoring postoperative pain in young children, by S Merkel and others, 1997, Pediatr Nurse 23(3), p. 293-297. Copyright 1997 by Jannetti Co. University of Michigan Medical Center. Reprinted with permission.

Riley Infant Pain Scale Assessment Tool Behavior/ Category 0 1 2 3 Facial Neutral/smiling Frowning/grimacing Clenched teeth Full cry expression

Body Movement

Calm, relaxed Restless/fidgeting Moderate agitation or moderate mobility

Thrashing, flailing, incessant agitation or strong voluntary immobility

Sleep Sleeping quietly with easy respirations

Restless while asleep Sleeps intermittently (sleep/awake)

Sleeping for prolonged periods of time interrupted by jerky movements or unable to sleep

Verbal/vocal No cry Whimpering, complaining

Pain crying Screaming, high-pitched cry

Consolability Neutral Easy to console Not easy to console Inconsolable

Response to movement/ Touch

Moves easily Winces when touched/moved

Cries out when moved/touched

High-pitched cry or scream when touched or moved

From Comparison of three preverbal scales for post operative pain assessment in a diverse pediatric sample, by JG Schade, BA Joyce, J Gerkensmeyer, and JF Keck, 1996, J of Pain and Symptom Management 12(6) p. 348-359. Copyright 1996 Elsevier Science Inc. Reprinted with permission.

Table 6. Developmental Differences in Pain Expression

Developmental Group Expressions of Pain

Infants May: �� Exhibit body rigidity or thrashing, may include arching �� Exhibit facial expression of pain (brows lowered and drawn together, eyes

tightly closed, mouth open and squarish) �� Cry intensely/loudly �� Be inconsolable �� Draw knees to chest �� Exhibit hypersensitivity or irritability �� Have poor oral intake �� Be unable to sleep

Toddlers May: �� Be verbally aggressive, cry intensely �� Exhibit regressive behavior or withdraw �� Exhibit physical resistance by pushing painful stimulus away after it is applied �� Guard painful area of body �� Be unable to sleep

Preschoolers/Young Children

May: �� Verbalize intensity of pain �� See pain as punishment �� Exhibit thrashing of arms and legs �� Attempt to push stimulus away before it is applied �� Be uncooperative �� Need physical restraint �� Cling to parent, nurse, or significant other �� Request emotional support (e.g. hugs, kisses) �� Understand that there can be secondary gains associated with pain �� Be unable to sleep

School-Age Children May: �� Verbalize pain �� Use an objective measurement of pain �� Be influenced by cultural beliefs �� Experience nightmares related to pain �� Exhibit stalling behaviors (e.g., “Wait a minute” or “I’m not ready”) �� Have muscular rigidity such as clenched fists, white knuckles, gritted teeth,

contracted limbs, body stiffness, closed eyes, or wrinkled forehead �� Include all behaviors of preschoolers/young children �� Be unable to sleep

Adolescents May: �� Localize and verbalize pain �� Deny pain in presence of peers �� Have changes in sleep patterns or appetite �� Be influenced by cultural beliefs �� Exhibit muscle tension and body control �� Display regressive behavior in presence of family �� Be unable to sleep

4. Physiologic Measures and Diagnostic Studies

Physiologic measures should only be used as adjuncts to self-report of pain and behavioral

observation. As with behavioral measures of pain, physiologic or biologic measures cannot

discriminate well between physical responses of pain and other forms of stress on the body.

Physiologic responses include: skin flushing; diaphoresis, elevated blood pressure, tachycardia,

tachypnea; decreased oxygen saturation; restlessness; and dilation of the pupils. There are marked

variations in the occurrence of these symptoms from patient to patient. A review of pertinent

diagnostic studies including imaging procedures and laboratory studies obtained to further evaluate

and determine the source of pain is critical to being able to effectively treat pain.

Key Points To Remember

Failure to assess pain is a critical factor leading to under treatment. Assessment should occur: At regular intervals after initiation of treatment. At each new report of pain. After pharmacologic or nonpharmacologic intervention, at an appropriate interval (e.g., 15-30 minutes after parenteral therapy, 1 hour after oral administration); Follow-up assessment is crucial.

It is essential to document the pain assessment on the patient’s medical record. When there is uncertainty about the presence or amount of pain even after using assessment

strategies as with infants or young children, a diagnostic trial of analgesics is appropriate.

V. Pharmacologic Pain Management

The current standard for the management of cancer pain in children consists of four

concepts: “by the ladder”, “by the clock”, “by the mouth”, and “by the child”. This means that

pain management in children should follow the World Health Organization Analgesic Stepladder,

be administered on a scheduled basis, be given by the least invasive route, and be tailored to the

individual child’s circumstance and needs (McGrath, 1996).

By the Ladder:

The WHO Analgesic Stepladder is a multi-step approach to treating pain, and is a guide for

initiating analgesic drugs and dosages that correspond to the patient’s reported level of pain (Figure

2). The ladder starts with non-opioid oral drugs for mild pain and progresses to strong opioids,

adjuvants and invasive therapies for severe and/or intractable pain. It is important to keep in mind

Figure 2. Therapeutic Ladder for Pain Management.

that the potency of analgesia should be matched to the child’s reported level of pain. For example,

if children report severe pain, they should be started on a potent opioid such as morphine. It would

be inappropriate to start a child with severe pain on ibuprofen or a weak opioid and progress up the

ladder from that point.

Analgesic Drugs:

NSAIDs / Acetaminophen

Non-steroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-pyretic, and anti-

inflammatory activity. NSAIDs act peripherally to provide their analgesic effect by interfering

with the synthesis of prostaglandin, through the inhibition of cyclooxygenase (COX). There are

two isoenzymes of COX; COX-1 and COX-2. The COX-1 isoform is expressed primarily in the

kidney, gastrointestinal tract and on platelets. In contrast, the COX-2 isoform is found in low

levels in tissues, but is induced during inflammation. By selectively inhibiting the COX-2

isoform, prostaglandin pathways are influenced, decreasing pain and inflammation and avoiding

the toxicities of the inhibition of COX-1. Most NSAIDs are non selective inhibitors of COX.

There are now two selective COX-2 inhibitors available (Table 7). However, there is limited

pediatric data for dosing and side effects of these selective COX-2 inhibitors.

The side effects of nonselective NSAIDs include decreased platelet aggregation, gastric

irritation, and the potential for renal toxicity with long term use. Children with low platelet

counts or who are neutropenic should be monitored carefully when taking nonselective NSAIDs

for pain relief. The nonselective NSAID choline magnesium trisalicylate does not interfere with

platelet aggregation, but its use should be avoided in children with platelet counts less than

20,000 or with active bleeding (Collins and Berde, 1997). Acetaminophen has similar analgesic

and antipyretic effects to the NSAIDs, but does not provide an anti-inflammatory effect.

Acetaminophen does not affect platelet function or irritate the stomach, but hepatic toxicity can

occur with high doses of acetaminophen (i.e., >75 mg/kg/day or 4 g/day).

Acetaminophen preparations are available with the opioid drugs codeine, oxycodone and

hydrocodone (Table 8). These combination drugs are beneficial for mild to moderate pain that

does not respond to acetaminophen or NSAIDs alone. When using acetaminophen in

combination with codeine or hydrocodone, it is important not to exceed the maximum daily

dose of the acetaminophen component of the drug (Table 7). If pain increases or persists

beyond the maximum dosage of a combination preparation, switching to a stronger opioid agent

would be the next step in managing a child’s pain. NSAIDs are limited to a ceiling dose where

increasing the dose only produces toxicity and no pain relief.

Table 7. Nonsteroidal Anti-Inflammatory Drugs Used for Cancer Pain Drug Type Typical Starting Dose Acetaminophen 10 to 15 mg/kg/dose q 4 hr PO to a max of 650 mg/dose

Aspirin 10 to 15 mg/kg/dose q 6 to 8 hr PO to a max of 650 mg/dose

Ibuprofen 10 mg/kg/dose to a max single dose of 800 mg q 6 to 8 hr PO

Choline magnesium trisalicylate 7.5 to 25 mg/kg/dose bid-tid; max single dose of 1500 mg PO

Diclofenac sodium 1 to 1.5 mg/kg/dose to a max single dose of 75 mg q 8 to 12 hr PO

Naproxen 5 to 7.5 mg/kg/dose to a max of 500 mg/dose q 12 hr PO

Naproxen sodium Same as Naproxen

Ketorolac 0.5 to 1 mg/kg as single dose IM to a max of 60 mg, followed by 0.5 mg/kg IV q 6 hr to a max single dose of 30 mg. Max duration is 5 days (useful in short term pain management). Limited data on use of oral Ketorolac in children

Celecoxib (Cox-2 inhibitor)

Rofecoxib (Cox-2 inhibitor)

100 mg to 200 mg PO q day for patients > 18 years. No information in patients < 18 years

12.5 mg PO q day for patients > 18 years; max: of 25 mg/day. No information for patients < 18 years

Opioids

Opioids bind with certain receptors (Mu, Kappa, Delta) in the CNS and peripheral

tissues to provide analgesic effects. Mu receptors are located in the CNS and provide central

analgesia, but also play a role in the development of respiratory depression, physical

dependence and withdrawal symptoms. Kappa receptors are located in greatest concentration in

the cerebral cortex and substantia gelatinosa of the dorsal horn. Kappa receptors are responsible

for analgesia at the level of the spinal cord and the brain, but have less of a role in physical

dependence and withdrawal. Delta receptors are concentrated in the substantia gelatinosa of the

dorsal horn and have a primary effect upon spinal and supraspinal analgesia.

Mu-agonist drugs are the most commonly used class of opioids, and include drugs such

as morphine, fentanyl, and codeine (Table 8). The analgesic effect of these drugs has no ceiling,

and dosing is limited only by the presence of unmanageable side effects (Leahy, Hockenberry-

Eaton, and Sigler-Price, 1994). Meperidine also falls into the class of Mu-agonists. However,

meperidine has fallen out of favor as an analgesic drug, due to its short duration of action and

the accumulation of a toxic metabolite normeperidine, which causes undesirable CNS side

effects, including seizures, at low doses of the drug. Meperidine should not be used for

chronic pain control in children. Depending on the opioid, they can be given orally, rectally,

as subcutaneous or intravenous infusions, intramuscularly, transdermally, and directly into the

CNS via epidural/caudal/intrathecal injection. The most common side effects of opioid

analgesia in children are constipation, sedation, pruritis, and nausea/vomiting. Respiratory

depression, although the most frequently cited concern of health care providers, is a relatively

rare occurrence. The risk of respiratory depression decreases significantly when children are on

opioid analgesics for prolonged periods of time. In the event mild respiratory suppression

occurs it is easily managed by awakening the child, giving oxygen, and decreasing further

opioid doses by 25%. In the event of severe respiratory depression, the American Pain Society

(1999) recommends using naloxone in small doses for children < 40 kg. They recommend a

dose of 0.5 mcg/kg IV every two minutes until respirations improve (Table 10). The important

issue to consider is the goal of a reversal agent is to improve respiratory status without

compromising pain management.

All opioids have the potential for tolerance, physical dependence, and addiction. The

phenomenon of drug tolerance must be separated from the fear of addiction in order to

appropriately use opioid therapy. Tolerance refers to the progressive decline in analgesic

potency and the need to increase doses of the opioid to achieve the same analgesic effect over

time. Tolerance also occurs to the side effects of opioids with long term administration,

particularly sedation and respiratory depression. Tolerance to these side effects is beneficial,

because doses can be increased to control pain without increased incidence of sedation or risk of

respiratory depression. Concerns about the development of tolerance should not lead the health

care provider to ‘save’ opioid drugs for later use. Tolerance is easily managed by increasing the

dose of the opioid, adding appropriate adjuvants, or switching to another opioid drug. Cross-

tolerance between opioids is incomplete; therefore, the dose for the new opioid should be

reduced up to 50% of the equianalgesic dose and re-titrated from there for adequate pain relief.

Table 8. Starting Doses and Conversion Factors for Commonly Prescribed Opioids

Drug Oral Starting Doses Dosage Forms Starting Doses IV

IV to PO

Codeine 0.5 to 1 mg/kg q 4 to 6 hr; max: 60 mg/dose

Tablet, as sulfate: 30 mg Liquid: 3 mg/mL

N/A N/A

Acetaminophen and Codeine

0.5 to 1.0 mg/kg/dose of codeine q 4 to 6 hr; max: 2 tablets/dose; 15 mL/dose

Elixir: acetaminophen 24 mg and codeine 2.4 mg/mL with alcohol 7%

Suspension: acetaminophen 24 mg and codeine 2.4 mg/mL alcohol free

Tablet: #3: acetaminophen 300 mg and codeine 30 mg

N/A N/A

Drug Oral Starting Doses Dosage Forms Starting Doses IV

IV to PO

Hydrocodone and Acetaminophen

3 to 6 years: 5mL 3 to 4 times/day

7 to 12 years: 10 mL 3 to 4 times/day

>12 years: 1 to 2 tablets q 4 to 6 hr; max: 8 tablets/day

Tablet: hydrocodone 5 mg and acetaminophen 500 mg

Oral solution at: 0.5 mg hydrocodone and 33.4 mg/mL acetaminophen

N/A

N/A

Oxycodone Instant release: 0.05 to 0.15 mg/kg/dose up to 5 mg/dose q 4 to 6 hr

Sustained release: for patient’s taking >20 mg/day of oxycodone can administer 10 mg q 12 hr

Instant release: 5 mg Sustained release: 10 mg, 20 mg,

40 mg, 80 mg

N/A N/A

Morphine 0.3 to 0.6 mg/kg/dose every 12 hr for sustained release

0.2 to 0.5 mg/kg/dose q 4

to 6 hr prn for solution of instant release tablets

Injection: 2 mg/mL, 5 mg/mL, 10 mg/mL, 15 mg/mL

Injection, preservative free: 1 mg/mL Solution: 2 mg/mL Tablet: 15 mg (instant release) Tablet, controlled release: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg

0.1 mg/kg/ dose 0.1 to 0.2 mg/kg/dose q 2 to 4 hr; max: 15 mg/dose

10 mg IV = 30 to 60 mg PO

Fentanyl

Lozenge: < 15 kg: contraindicated > 2 years (15 kg to 40 kg):

5 to 15 mcg/kg; max: dose 400 mcg

> 40 kg: 5 mcg/kg; max: dose of 400 mcg

Transdermal: See Table

12

Lozenge: 100 mcg, 200 mcg, 300 mcg, 400 mcg

Patch: 25 mcg/hr, 50 mcg/hr, 75

mcg/hr, 100mcg/hr Injection: 50 mcg/mL

1 to 2 mcg/kg/dose; max: 50 mcg/ dose Continuous IV infusion: 1 mcg/kg/hr

N/A

Hydromorphone 0.03 to 0.08 mg/kg/dose PO q 4 to 6 hr; max: 5 mg/dose

Injection: 1, 2, 3 and 4 mg/mL Tablet: 2 mg, 4 mg Syrup: Hydromorphone 1mg and guafenesin 100 mg/5 ml

Suppository: 3 mg

15 mcg/kg IV q 4 to 6 hr; max: 2 mg/dose

1.5 mg IV = 7.5 mg PO

Methadone 0.1 to 0.2 mg/kg q 4 to 12 hr; max: 10 mg/ dose

Tablet: 5 mg, 10 mg Solution: 1 mg/mL Concentrate: 10 mg/ml Injection: 10 mg/mL

0.1 mg/kg IV q 4 to 12 hr; max: 10 mg

10 mg IV = 20 mg PO

Adjuvants

Adjuvant drugs are used in combination with non-opioid and opioid drugs to enhance pain

management, and are used more frequently in complicated neuropathic pain syndromes.

Adjuvant drugs can by divided into two categories: co-analgesic drugs and drugs that treat side

effects. Co-analgesics include drugs from a variety of classes, including antidepressants,

anticonvulsants, corticosteroids and sedative/hypnotics (Table 9). Drugs used to treat side effects

include antihistamines, psychostimulants, laxatives, neuroleptics, and antiemetics (Table 10).

Table 9. Co-analgesic Adjuvant Drugs

Category/Drug Dosage Indication Comments ANTIDEPRESSANTS

Amitriptyline

0.2 to 0.5 mg/kg PO hs Titrate upward by 0.25 mg/kg every 5 to 7

days as needed Available in 10 mg and 25 mg tablets Usual starting dose is 10 to 25 mg

Continuous neuropathic pain with burning, aching, dysthesia with insomnia

Provides analgesia by blocking re-uptake of serotonin and norepinephrine possibly slowing transmission of pain signals

Helps with pain related to insomnia and depression (use nortriptyline if patient is over-sedated)

Analgesic effects seen earlier than antidepressant effects

Side effects include dry mouth, constipation, urinary retention

Nortriptyline

0.2 to 1.0 mg/kg PO a.m. or bid Titrate up by 0.5 mg q 5 to 7 days Max: 25 mg/dose

Neuropathic pain as above without insomnia

ANTICONVULSANTS

Gabapentin

5 mg/kg PO at bedtime Increase to bid on day 2, tid on day 3 Max: 300 mg/day

Neuropathic pain Mechanism of action unknown. Side effects include sedation, ataxia,

nystagmus, dizziness

Carbamazepine

<6 years 2.5 to 5 mg/kg PO bid initially Increase 20 mg/kg/ 24 hr divide bid q

week prn; max: 100 mg bid 6 to 12 years 5 mg/kg PO bid initially Increase 10 mg/kg/24 hr divide bid q week

prn to usual max: 100 mg/dose bid >12 years 200 mg PO bid initially Increase 200 mg/24 hr divide bid q week

prn to max: 1.6 to 2.4 gm/24 hr

Sharp, lancinating neuropathic pain

Peripheral neuropathies

Phantom limb pain

Similar analgesic effect as amitriptyline

Monitor blood levels for toxicity only

Side effects include decreased blood counts, ataxia, and GI irritation

ANXIOLYTICS

Lorazapam 0.03 to 0.1 mg/kg q 4 to 6 hr PO / IV; max: 2 mg/dose

Muscle spasm Anxiety

May increase sedation in combination with opioids

Can cause depression with prolonged use

Diazapam 0.1 to 0.3 mg/kg q 4 to 6 hr PO / IV; max: 10 mg/dose

CORTICOSTEROIDS Dexamethasone Dose dependent on clinical situation;

higher bolus doses in cord compression, then lower daily dose. Try to wean to NSAIDs if pain allows

Cerebral edema: 1 to 2 mg/kg load then 1 to 1.5 mg/kg/day divided every 6 hr; max: 4 mg/dose

Anti-inflammatory: 0.08 to 0.3 mg/kg/day

divided every 6 to 12 hr

Pain from increased intercranial pressure

Bony metastasis Spinal/nerve

compression

Side effects include edema, gastrointestinal irritation, increased weight, acne

Use gastroprotectants such as H2 blockers (ranitidine) or proton pump inhibitors such as omeprazole for long-term administration of steroids or NSAIDs in end-stage cancer with bony pain

OTHERS

Clonidine 2 to 4 mcg/kg PO q 4 to 6 hr May also use a 100 mcg transdermal patch

q 7 days for patients > 40 kg

Neuropathic

pain. Lancinating,

sharp, electrical, shooting pain.

Phantom limb pain

Alpha 2 adenoreceptor agonist modulates ascending pain sensations

Routes of administration include oral, transdermal, and spinal

Management of withdrawal symptoms

Monitor for orthostatic hypertension, decreased HR

Sedation common

Mexiletine 2 to 3 mg/kg/dose PO tid may titrate 0.5 mg/kg q 2 to 3 weeks as needed max: 300 mg/dose

Similar to lidocaine, longer acting Stabilizes sodium conduction in

nerve cells, reduces neuronal firing

Can enhance action of opioids, antidepressants, anticonvulsants

Side effects include dizziness, ataxia, nausea, vomiting

May measure blood levels for toxicity

Side Effects

Opioids have side effects that can create discomfort for children. The most commonly

occurring side effects include constipation, sedation, pruritis, and nausea/vomiting.

Constipation can become a troublesome side effect of opioid analgesic use. Children on opioids

should be immediately started on a stool softener combined with a mild peristaltic stimulant in

an effort to prevent constipation. Constipation can be treated by recommending increased fiber

such as bran cereals and fluids such as prune juice, however this is often unpalatable in children.

Severe constipation, caused by inhibition of peristalsis from the opioids, may require the use of

a stimulating cathartic drug (Table 10). Enemas and suppositories, rarely used in children with

cancer, are administered when other measures have not relieved the problem. The following

guidelines can be used to prevent and manage constipation caused by opioid use.

• Routinely assess the patient's usual bowel habits, use of laxatives and date of last bowel

movement. Optimally, bowel movements should occur a minimum of every 2 days.

• Encourage fluids and fiber products (i.e., water, prune juice, fruits, bran products), but do not

force their use. They can worsen symptoms in the presence of an impaction.

• Begin stool softener or laxative at initiation of opioid use (i.e., Senokot-S®); use of a combined

laxative and stool softener (i.e., Peri-Colace®) should be started if bowel movements are less

frequent than every 2 days.

• Titrate the medications dependent upon the number of bowel movements. For children on long-

term and/or high doses of opioids, constipation can become a chronic problem. If a child has

not had a bowel movement in greater than 3 days despite oral laxatives and softeners, consider

the use of a suppository (i.e., glycerin or bisacodyl). If constipation persists, a strong cathartic

such as oral magnesium citrate or enema may be indicated.

Uncommon side effects of opioids include respiratory depression, seizures, dry mouth,

myoclonus and urinary retention. If a child is receiving a dosage of an opioid analgesic that

provides pain relief but is accompanied by an undesirable side effect, consider switching to

another opioid in equianalgesic dose or add a drug to treat the side effect.

Table 10. Management of Opioid Side-Effects

Side Effect Adjuvant Drugs Nonpharmacologic Techniques

Constipation Senna and docusate sodium: Tablet: 2 to 6 years Start: ½ tablet once a day; max: 1

tablet twice a day 6 to 12 years Start 1 tablet once a day; max: 2

tablets twice a day > 12 years Start 2 tablets once a day; max: 4

tablets twice a day Liquid: 1 month to 1 year: 1.25 to 5 mL q hs 1 to 5 years = 2.5 to 5 mL q hs 5 to 15 years = 5 to 10 mL q hs > 15 years = 10 to 25 mL q hs

Casanthranol and docusate sodium Liquid: 5 to 15 ml q hs Capsules: 1 cap PO q hs

Bisacodyl: PO or PR 3 to 12 years 5 mg/dose/day > 12 years 10 to 15 mg/dose/day

Lactulose: 7.5 mL/day after breakfast Adult: 15 to 30 mL PO q day

Mineral oil: 1 to 2 tsp PO/ day Magnesium Citrate:

< 6 years = 2 to 4 mL/kg PO once 6 to 12 years = 100 to 150 mL PO once > 12 years = 150 to 300 mL PO once

Milk of Magnesia (MOM) < 2 years = 0.5 mL/kg/dose PO once 2 to 5 years = 5 to 15 mL PO q day 6 to 12 years = 15 to 30 mL PO once > 12 years = 30 to 60 mL PO once

Increase water intake Prune juice, bran cereal,

vegetables

Sedation Caffeine: single dose of 1 to 1.5 mg PO Dextroamphetamine: 2.5 to 5 mg PO in a.m. and

early afternoon Methylphenidate: 2.5 to 5 mg PO in a.m. and early

afternoon Consider opioid switch if sedation is persistent

Caffeinated drinks (i.e., Mountain Dew, cola drinks)

Nausea/Vomiting Promethazine: 0.5 mg/kg q 4 to 6 hr; max: 25 mg/dose

Ondansetron: 0.1 to 0.15 mg/kg IV or PO q 4 hr; max: 8 mg/dose

Granisetron: 10 to 40 mcg/kg q 2 to 4 hr; max: 1 mg/dose

Droperidol: 0.05 to 0.06 mg/kg IV q 4 to 6 hr; can

Imagery, relaxation Deep, slow breathing

Side Effect Adjuvant Drugs Nonpharmacologic Techniques

be very sedating

Pruritus Diphenhydramine: 1 mg/kg IV / PO q 4 to 6 hr prn; max: 25 mg/dose

Hydroxyzine: 0.6 mg/kg/dose PO q 6 hr; max: 50 mg/dose

Naloxone: 0.5 mcg/kg/hr continuous infusion (diluted in a solution of 0.1 mg of naloxone per 10 ml of saline)

Butorphanol: 0.3 to 0.5 mg/kg IV (use cautiously in opioid tolerant children, may cause withdrawal symptoms); max: 2 mg/dose because mixed agonist/antagonist

Oatmeal baths, good hygiene

Exclude other causes of itching

Change opioids

Respiratory depression: Mild—moderate

Hold dose of opioid Reduce subsequent doses by 25%

Arouse gently, give O2, encourage to deep breath

Respiratory depression: Severe

Naloxone: During Disease Pain Management:

0.5 mcg/kg in 2 minute increments until breathing improves (APS, 1999; McCaffery and Pasero, 1999)

Reduce opioid dose if possible Consider opioid switch

During Sedation for Procedures: 5 to 10 mcg/kg until breathing improves (Yaster, 1997, Taketomo, Hodding and Kraus, 1997-98)

Reduce opioid dose if possible Consider opioid switch

O2, bag and mask if indicated

Dysphoria/confusion /hallucinations

Evaluate medications, eliminate adjuvant medications with CNS effects as symptoms allow

Consider opioid switch if possible Haloperidol (Haldol®): 0.05 to 0.15 mg/kg/day

divided in 2 to 3 doses; max: 2 to 4 mg/day

Rule out other physiologic causes

Urinary retention Evaluate medications, eliminate adjuvant medications with anticholinergic effects; i.e., antihistamines, tricyclic antidepressants

Occurs with spinal analgesia more frequently than with systemic opioid use

Oxybutynin: 1 year = 1 mg tid 1 to 2 years = 2 mg tid

2 to 3 years = 3 mg tid

4 to 5 years = 4 mg tid

> 5 years = 5 mg tid

Rule out other physiologic causes

In/out or in-dwelling urinary catheter

By the Clock

One of the most common causes of under-medication of children with analgesic drugs is the

use of PRN (pro re nata or “as needed”) dosing schedules. The goal of pain management is to

optimize pain relief while minimizing undesirable side effects. When analgesics are administered

on a scheduled basis a steady therapeutic state is achieved, providing consistent pain relief, and

allowing for tolerance to side effects to develop. When a PRN schedule is used, analgesia is

frequently administered in a random pattern. This results in brief periods of pain relief followed by

potentially long periods of pain with increasing undesirable side effects. PRN dosing has been

found to be ineffective as the only method of pain management, but can be appropriate when used

to provide extra doses of a regularly scheduled analgesia to treat ‘breakthrough’ pain (i.e., episode

of intense or severe pain).

By the mouth

The route used to administer medication to children must be carefully considered.

Generally, the least invasive route should be used to administer analgesic medications. Children

present a special challenge in administering medications depending on their age, level of

cooperation, and temperament. If taking medication becomes a struggle, children and parents will

often under report pain to avoid the trauma of taking or giving the medicine.

Routes of Administration

Oral/Sublingual

Children who are able to swallow tablets can achieve excellent pain control with oral

medications, and this route should be the first choice for administration of analgesic medication.

Oral sustained release preparations such as MS-Contin and Oxy-Contin are popular choices due to

the long lasting effects, approximately 8 to 12 hours (DO NOT CRUSH OR CHEW). Fentanyl a

drug used for procedural pain, is now commercially available in a transmucosal lozenge (lollipop)

preparation and has proved to be an effective way to administer medication to children.

Unfortunately, most liquid medication used to manage pain in young children can be unpalatable.

A compounding pharmacist can be very helpful in providing medications in a flavored suspension

or lozenge (troche) form that makes the medication more palatable to young children. In addition, a

compounding pharmacist can formulate medications to be administered by different routes. For

information about specially compounded medications ask your pharmacist or seek national

assistance from: Professional Compounding Centers of America (PCCA), [phone 800-331-2498;

www.thecompounders.com] and the International Academy of Compounding Pharmacists (IACP).

Oral opioids undergo a ‘first pass effect’ in the liver, which requires that oral doses be

higher than parenteral doses. Drugs that can be administered sublingually prevent the first pass

effect as the drug is absorbed directly into the bloodstream and provides a more rapid effect. When

changing from parenteral administration to oral administration of opioid analgesics, health care

providers must calculate the appropriate dosage adjustment to maintain equal analgesic strength to

the parenteral dose to assure adequate pain control (Table 12).

Rectal

Many drugs are available in rectal suppositories, however absorption of drugs by the rectal

route can be inconsistent. The rectal route is also contraindicated in children with neutropenia or

thrombocytopenia because of the risk of infection or bleeding. Generally, children find the

administration of suppositories uncomfortable and invasive. It is not a preferred route if there are

other less invasive routes available.

Transdermal/Topical

Fentanyl patches are the only commercially available opioid in a transdermal preparation.

Onset of action is slow, over 12-18 hours for the first dose, and each patch has a duration of 72

hours before the patch needs to be changed. This route is not useful for rapid dose titration for a

child who is experiencing escalating or severe pain, and is most appropriately used to switch a

patient from oral or parenteral routes who has achieved pain control on another opioid analgesic.

Oral doses of an immediate-release opioid should be continued on a PRN basis for breakthrough

pain.

Intramuscular

The intramuscular route should be avoided in administering analgesic medication to a child.

Children instinctively fear ‘shots’ and will not report pain if they believe they will be given an

injection as a result.

Subcutaneous

Most of the medications used for pain management are available in parenteral form and can

be given as a continuous subcutaneous (SC) infusion. For children who cannot take oral

medications and have no intravenous access, this route is an acceptable alternative and provides

excellent pain control. EMLA® (prilocaine/lidocaine) or other topical agents, such as vapocoolants

or Numby Stuff®, should be used to anesthetize the site prior to inserting the subcutaneous needle

or cannula, making the procedure virtually painless (preparation for invasive procedures p. 44).

Numby Stuff®, an iontophoretic drug delivery system, utilizes an electrical current to facilitate

local dermal anesthesia. Active drug ions are transported into the skin by an electrical current being

passed through dermal patches.

Intravenous

Oral analgesic medications should be given for as long as the child is able and willing to

take them, and as long as the pain can be adequately controlled. However, for children with

analgesic dose requirements that exceed reasonable oral dosing, or for whom oral medications are

not tolerated, the intravenous route is the most appropriate. Patient, parent, or nurse controlled

analgesia (PCA) pumps can be used both in the hospital setting and at home for subcutaneous and

intravenous administration of analgesic medications (Table 11). Many PCA pumps available for

use at home are small and allow the child to remain ambulatory.

Epidural/Caudal/Intrathecal

When high doses of systemic opioids are ineffective in relieving pain or are causing

intolerable side effects (severe constipation, myoclonus, excessive nausea/vomiting), administration

of analgesics via the epidural or intrathecal route will often relieve pain. Administration of analgesia

through an indwelling epidural/caudal/intrathecal catheter directly inhibits pain at very low doses,

thereby reducing undesirable side effects. Decisions regarding patient eligibility, level of catheter

placement, and appropriate drugs and doses should be made in consultation with an anesthesiologist

and according to institutional policies.

By the child

The needs of the individual child must be taken into account when determining dosages of

pain medications. There is not a standard dose that will work for all children. The goal is to provide

each child with the dose of analgesic medication that prevents recurrence of pain prior to the next

dose, keeping the child pain-free (McGrath, 1996). Health care providers must be educated and

provide information to patients and families regarding the appropriate medical use of opioids as

analgesic agents.

Dosing

Selecting an initial dose of opioid analgesic depends on the child’s prior exposure to opioids,

the severity of the pain and route of administration. When initiating analgesic therapy in children

with no prior exposure to opioids, follow the recommended dosage range for the selected opioid

outlined in Table 8. For children with severe pain, it is necessary to titrate the opioid dose

frequently to achieve pain relief as quickly as possible. One method to accomplish this goal is to

start with a short acting opioid such as immediate-release oral morphine, and instruct the family to

give a dose every 2 hours as needed for the first 24 to 48 hours. The total daily dose the patient

required to achieve pain relief is then calculated, and converted to an equivalent dose of an extended

release drug such as MS Contin® or a fentanyl patch. It is important to continue to provide rescue

doses of medication in immediate release form whenever an extended relief form of opioid is used.

Patient controlled analgesia (PCA) offers a highly effective and efficient method for the

treatment of moderate to severe pain (Table 11). For children who are prescribed PCA pumps, a

similar method to titrate the dose as with that of oral morphine is used by the bolus function of the

PCA. A child should be started with a loading dose, if needed, of 0.05 to 1 mg/kg, followed by a

moderate basal rate, 0.01 to 0.2 mg/kg/hr of morphine, with boluses of 0.015 to 0.025 mg/kg

available every 10 to15 minutes. The PRN use should be evaluated on an hourly basis. If a child

experiences persistent or worsening pain on a current dose of opioid, increase the dose by 50% and

re-evaluate within an hour if the dose is given by mouth. When the opioid is given intravenously,

pain assessment should be within 15 minutes of administration. Continue to increase dose by 50%

to 100% q 1 to 2 hours, depending on severity of pain and re-evaluate until comfort is achieved.

Adjust the basal dose of opioids accordingly. After 24 hours the total dose is calculated and the

basal rate adjusted to meet the patient’s demands. It is important that the child and family

understand the use of PRN or bolus doses, and administer additional doses until the pain is under

control. The goal is to stay ahead of the pain, as opposed to ‘chasing’ the pain.

Table 11. Patient Controlled Analgesia– (Morphine)

PCA Programming Purpose Initial Dose Recommendations Loading dose Obtain immediate pain control 0.05 to 0.1 mg/kg; max: 10 mg

Background infusion (basal rate)

To maintain continuous pain relief 0.01 to 0.02 mg/kg/hr

Interval dose A bolus interval dose will allow the patient to titrate his/her own pain control

0.015 to 0.025 mg/kg

Lockout To prevent overdose in an opioid naïve patients

6 to 15 minutes

Four-hour maximum To avoid overdose in an opioid naïve patient. Assess q hr to determine adequate pain management and adjust dose as necessary (McCaffery, 1999)

0.25 to 0.35 mg/kg

Equianalgesic Conversions

The dose of one analgesic drug that is equivalent in pain relieving potential to another

analgesic drug is referred to as an equianalgesic dose. The standard equianalgesic conversion is

based on the pain relieving potential of 10 mg of parenteral morphine. To convert from the oral

route to another route, or from one opioid to another, find the equianalgesic dose of the present

opioid and the opioid you wish to convert in the equianalgesic table (Table 12). Multiply the 24

hour dose of the current drug by the dose of the new opioid from the equianalgesic table. Then

divide by the dose of the new opioid. This will give you the 24 hour dose of the current opioid.

The following example takes you through the conversion process from PO sustained release

morphine to IV hydromorphone.

Example: Johnny is taking sustained release morphine at a dose of 30 mg PO q 8 hr. He is having difficulty swallowing and the plan is to change to IV hydromorphone as a continuous intravenous infusion. Step 1: Begin by calculating the 24 hour oral morphine requirement He has been receiving 30 mg every 8 hours or times a day:

30 mg x 3 times a day = 90 mg q 24 hr Step 2: Next convert the 90 mg of oral morphine Johnny is taking each day to an equianalgesic dosage of IV morphine IV 10 mg IV = X mg IV morphine = 10 x 90 = 900 To PO 60 mg PO 90 mg PO morphine/24 hr 60 60 X = 15 mg IV morphine/24 hr

Step 3: Now convert the 24 hour IV morphine dose to the 24 hour hydromorphone dose 10 mg IV morphine = 15 mg IV morphine (1.5 x 15) = X 1.5 mg IV hydromorphone X mg IV hydromorphone 10 X = 2.25 mg IV hydromorphone (24 hr dose) Step 4: Take the 24 hour calculated dose and divide by 24 to get the hourly dose The new dose of IV hydromorphone = 2.25 mg/24 hr 2.25 = 0.1 mg/hr IV hydromorphone 24

Table 12. Equianalgesic Conversion Table

Drug

Onset (min) Peak(h) 1 ½ (h) EquianalgesicDoses †

IV/IM Oral

(mg) (mg) Codeine 10-30 0.5-1 3 120 200 Fentanyl 7-8 ND 1.5-6 0.1 NA Hydrocodone ND ND 3.3-4.5 ND ND Hydromorphone 15-30 0.5-1 2-3 1.5 7.5 Methadone 30-60 0.5-1 15-30 10 20 Morphine 15-60† 0.5-1 1.5-2 10 60 Oxycodone, P.O. 15-30 1 ND NA 30 Oxymorphone 5-10 0.5-1 ND 1 10# From: Texas Children’s Hospital, Pharmacy Department: Drug information and formulary, ed 5, Hudson, Ohio, 1999, Lexi-Comp. Adapted with permission.

ND = no data available; NA = not applicable † Based on acute, short-term use. Chronic administration may alter pharmacokinetics and decrease the oral:parenteral

dose ratio. The morphine oral:parenteral ratio decreases to 1.5-2.5:1 upon chronic dosing. # Rectal. I.V. administration is most reliable and rapid; I.M. or S.C. use may cause delayed absorption and peak effect. especially with impaired tissue perfusion. Many agents undergo a significant first-pass effect. All are metabolized by the liver and excreted primarily in urine. Meperidine is metabolized to normeperidine, a metabolite with significant pharmacologic activity. The half-life of normeperidine is 15-30 hours and accumulates with chronic dosing, especially in patients with renal dysfunction. The accumulation of the metabolite may lead to CNS excitation (e.g., tremors, twitches, seizures).

Table 13. Equianalgesic Doses for Converting

Morphine to Transdermal Fentanyl1

Oral 24-Hr Morphine (mg/day)

IM 24-Hr Morphine (mg/day)

Duragesic® Dose (µg/hr)

45-134 8-22 25

135-224 23-37 50

225-314 38-52 75

315-404 53-67 100

405-494 68-82 125

495-584 83-97 150

585-674 98-112 175

675-764 113-127 200

765-854 128-142 225

855-944 143-157 250

945-1034 158-172 275

1035-1124 173-187 300

1The analgesic activity ratio of 10 mg IM morphine to 100 mcg IV fentanyl was used to derive the equivalence of morphine to Duragesic. A 10 mg IM or 60 mg oral dose of morphine every 4 hr for 24 hr (total of 60 mg/day IM or 360 mg/day oral) was considered approximately equivalent to Duragesic 100 mcg/hr.

From Janssen Pharmaceutica, Inc., Fentanyl Duragesic®, product insert, 1997. Adapted with permission.

Tapering Opioids

When a patient is ready to stop an opioid and has received the opioid for more than 3 weeks,

it is advisable to taper the medication. The opioid should be decreased by 20% every other day. If

the patient has signs and symptoms of withdrawal (flu-like symptoms, abdominal cramping,

diarrhea), the dose may need to be decreased in smaller amounts over a longer period of time.

Other opioids may need to be tapered even more slowly such as bezodiazapene which should be

decreased by 10% every 3 days (McCaffery, 1999).

Management of Complex Pain Problems

The majority of children with cancer pain can experience complete relief of pain using the

previous discussed agents. However a small number of children, particularly those with extensive

bony tumor metastasis and/or nerve involvement, may require more invasive pain management

techniques. Children with complex pain problems require thorough consideration of the

pathogenesis of the pain and consultation with a variety of specialty services who are experienced in

the management of pain in children. Clear communication with the child and family as to the goals

of any potential interventions is essential. When considering invasive therapies to control pain, the

risks and discomforts associated with the procedure must be weighed against the likelihood of pain

relief for the child.

Palliative Chemotherapy/Radiation Therapy

Intractable pain from increased tumor bulk, that is not responding to increasing doses of opioids,

may be responsive to palliative chemotherapy or radiation. The patient and family must understand

the goal of treatment with these modalities and consent to their use. Palliative chemotherapy can

be effective in reducing pain and symptoms if the tumor is still chemosensitive. The least toxic

drug and dose is used, and side effects are aggressively managed. Palliative radiation therapy can

be very effective in relieving localized pain from extensive bony metastasis, bone marrow disease,

and/or nerve compression.

Therapeutic nerve blocks

Tumors that are compressing nerves in a specific area can lead to intense focal pain. The use

of locally administered anesthetic nerve blocks can provide immediate relief from pain that is

otherwise not responsive to other less invasive techniques. Neuroablation with alcohol or phenol

can permanently destroy individual nerves. These interventions are used only in extreme cases of

nerve entrapment and excruciating pain when other interventions have failed. There is no assurance

that such blocks or ablative techniques will provide complete or permanent relief. When successful,

pain relief can be immediate. Gradual discontinuation of opioids and monitoring for respiratory

suppression and withdrawal symptoms should be the primary focus of care after such procedures.

Terminal Sedation

In very rare circumstances, children may experience such unrelenting pain or other

symptoms, that the need for sedation may be considered. Sedation is generally indicated when pain

and distress cannot be controlled by any other means either due to limited timeframe or risk of

excessive morbidity. The health care professional must determine what are truly uncontrollable

pain or symptoms versus under-treated pain and/or symptoms. It is important that prior to

considering sedation, all efforts have been made to achieve pain and symptom control.

Sedation must not be confused with euthanasia. Euthanasia refers to the active intent by

another person to end a terminally ill person’s life for the sake of compassion or mercy. The

ethical principle of double effect clarifies such issues. Double effect states that some interventions

have risks and benefits associated with them. If the intent is to provide benefits (pain relief), then

the risks (respiratory depression, death) are acceptable. The goal of sedation is to relieve obvious

pain and suffering of the child by adding drugs to induce sleep, but does not intend to hasten death.

Presenting the option of sedation to a child and family requires a caring, open relationship

between the treating health care professionals and the family. If the child and family are opposed to

sedation, they should be reassured that all efforts to gain control of pain and distress will continue.

If the child and family choose sedation, there are a number of pharmacological agents available to

produce the desired level of relief. It is important to recognize that sedation alone does not provide

analgesia, and a level of opioid analgesia that provides the most comfort possible should be

continued while the child is sedated. Consultation with a hospice physician would be appropriate to

determine the clinical appropriateness and best agents to use to achieve the desired comfort goals of

the child and family.

VI. Procedure-Related Pain Management

Invasive procedures are documented as the most painful and traumatic events experienced

by children. Although procedure-related pain represents an acute, short-lived experience, it is

accompanied by a great deal of fear and anxiety. For example, researchers have reported that bone

marrow aspirations/biopsies and lumbar punctures are perceived as extremely painful by children

with cancer (Broome, Rehwaldt and Fogg, 1998; Broome and others 1990). Previous studies have

shown that children do not adapt to the discomfort associated with intrusive procedures, but

experience greater levels of anxiety with repeated painful experiences (Zeltzer, 1990). Children

often experience symptoms such as depression, insomnia, and anorexia before the clinic or hospital

visit which will include a procedure. Consensus among professionals caring for children with

cancer supports a developmental approach to managing pain associated with procedures in children

with cancer. The goal is to provide comfort and support during all procedures experienced by the

child with cancer. The Consensus Conference on the Management of Pain in Childhood Cancer has

established the following principles that apply to all children undergoing painful interventions

(Table 14).

Table 14. Managing Childhood Procedure Related Pain

1. Prepare the child and parent(s) with specific interventions.

2. Provide maximum treatment of pain and anxiety for the initial procedure to reduce the development of subsequent anticipatory anxiety symptoms.

3. Provide adequate knowledge of behavioral and pharmacologic treatment of acute pain and anxiety by medical staff responsible for procedures.

4. Use appropriate monitoring and resuscitative equipment in the procedure room when using sedation.

5. Assure adequate mechanical skill in individuals who plan to perform pediatric procedures.

6. Provide ongoing evaluation of the child to assess efficacy of treatment for pain and anxiety.

7. Create as pleasant an environment as possible in the treatment room.

From: Report of the Subcommittee on the Management of Pain Associated With Procedures in Children with Cancer, by LK Zelter, and others, 1990. Pediatrics, 86(5), p 827. Copyright 1990 American Academy of Pediatrics. Adapted with permission

Goals of Procedural Pain Management (Schechter, Berde and Yaster, 1993)

There are three goals associated with successful procedural pain management. All require the early determination of appropriate outcomes. These three goals include: Minimize pain – coordinate painful procedures such as blood drawing and lumbar punctures; limit the number of attempts for a procedure. Maximize patient cooperation – early preparation of parent and child with information, role playing, and audio visual aids can be of benefit. Minimize risk to the patient – adequate monitoring and resuscitative equipment must be available and operational; pulse oximetry is a necessity; psychologic intervention can help to reduce need for pharmacologic agents.

Interventions

• During the course of treatment, children will frequently undergo invasive procedures which can

often be painful; for this reason, it is essential that the child be able to cope with this situation.

The first and most essential intervention is to prepare the child and family for the painful

procedure. The use of dolls to teach the younger child about what will occur during the

procedure can help to relieve some of the child’s anxiety and dispel misconceptions the child

may have. In addition, parents may benefit from written educational information, as well as a

review of the procedure and what to expect.

• The use of EMLA® cream (prilocaine/lidocaine) or anesthetic disc has proven successful in the

relief of procedure related pain. EMLA® cream or anesthetic disc is a topical anesthetic which

effectively penetrates intact skin and should be applied one to one and a half hours, but not

longer than four hours, before the procedure is to occur.

• For patients who receive a bone marrow aspirate or biopsy, buffered lidocaine may provide

subcutaneous analgesia that penetrates deeper than EMLA. The purpose of buffering lidocaine

is to alter the pH with an alkaline solution so that there is less burning with the injection. To

buffer the lidocaine, add 0.2 mL of sodium bicarbonate to 2 mL of lidocaine. Inject the buffered

lidocaine slowly into the subcutaneous tissue, using a 25 gauge needle. Wait two minutes, then

change the needle to a larger gauge and inject the lidocaine directly into the surface of the

periosteum. Wait an additional two to three minutes. This waiting time allows the lidocaine to

numb the area.

Pharmacologic management of procedural pain should provide both analgesia and sedation.

A pharmacologic approach known as conscious sedation is currently favored in many institutions.

The American Academy of Pediatrics defines conscious sedation as “a minimally depressed level of

consciousness that retains the patient’s ability to maintain a patent airway independently and

continuously, and respond appropriately to physical stimulation and/or verbal command” (AAP,

1992). Conscious sedation can be achieved with a variety of pharmacologic approaches (Table 15),

most of which combine an opioid analgesic with a benzodiazepine for anxiolysis and sedation. The

mixture DPT (Demerol, Phenergan, Thorazine) or Kiddie Cocktail administered

intramuscularly in many institutions for years as sedation is no longer recommended as the injection

is painful, and, most importantly, the drug combination is associated with a high incidence of side

effects. An opioid and/or benzodiazepine can be titrated to an individual patient’s response and

reversed with available agonists (naloxone: 5 to 10 mcg/kg/dose and flumazenil: 0.2 mg/dose). It is

critical for the practitioner sedating the child for a painful procedure to be familiar with the

pharmacokinetics and pharmacodynamics of the drugs selected in order to anticipate the onset and

duration of expected side effects.

Table 15. Examples of Sedation Medications

Drug Dosing Side-Effects Reversal Agents CONSCIOUS SEDATION: Midazolam: A Benzodiazepine (short acting), CNS depressant Onset: 1 to 5 minutes Peak Effect: 3 to 5 minutes (IV) Half Life: 1.5 to 12 hr

Oral: 0.2 to 1 mg/kg; 30 to 45 minutes before procedure; max: 20 mg IV: 0.05 mg/kg 3 minutes before procedure (may repeat dose X 2); max: 2 mg/dose

Respiratory distress, depression, apnea, PVC's, amnesia, blurred vision, or hyperexcitibility

Flumazenil: 0.2 mg/dose q 1 minute; max cumulative = 1 mg

Fentanyl: A Narcotic analgesic Onset: 1 to 5 minutes Peak Effect: (no data available) Half Life: 1.5 to 6 hr

IV: 0.5 to 3 mcg/kg/dose; may repeat after 30 to 60 minutes; max: 50 mcg/dose Use lower doses (0.5 to 1 mcg/kg/dose) when used in combination with other agents, such as midazolam

Respiratory distress or depression, apnea, seizures, shock, chest wall rigidity (most likely to occur with rapid infusion or high doses)

Naloxone: 5 to 10 mcg/kg/dose; Single dose should not exceed max recommended adult dose of 0.2 mg (Taketomo, Hodding and Kraus, 1997-98)

Morphine: A Narcotic Analgesic Onset: 15 to 60 minutes Peak Effect: 30 minutes to 1 hr Half Life: 1.5 to 2 hr

IV: 0.05 to 0.1 mg/kg 5 minutes prior to procedure; max: 15 mg/dose

Sedation, somnolence, respiratory distress or depression, pruritis

Naloxone: 5 to 10 mcg/kg/dose; Single dose should not exceed max recommended adult dose of 0.2 mg (Taketomo, Hodding and Kraus, 1997-98)

UNCONSCIOUS SEDATION: Propofol: A General anesthetic Onset: within 30 seconds

IV: 1 to 2 mg/kg followed by 75 to

100 mcg/kg/minute (Only with qualified anesthesia

Pain on injection, involuntary movements, hypotension, apnea

None

Drug Dosing Side-Effects Reversal Agents Peak Effects: 3 to 10 minutes Half Life: 3 compartment model:

initial: 2 to 8 minutes

2nd Distribution: 40 minutes

terminal: 200 minutes

personnel available)

Ketamine: A General anesthetic Onset: 30 seconds with IV administration; PO 20 to 45 minutes Peak Effects: 5 minutes Half Life: unknown

Oral: 6 to 10 mg/kg given 30 minutes prior to procedure IV: 0.25 to 0.75 mg/kg (Only: with qualified anesthesia personnel available)

Laryngospasm, severe hypo/hypertension, respiratory depression, apnea, excessive salivation

None

• There is the potential for pediatric patients to develop a syndrome referred to as “late sedation”

with these conscious sedation medications. Late sedation can occur even when the child does

not seem to be sedated at the end of the procedure, and can be due to continued drug uptake,

delayed excretion, pharmacodynamics, or the lack of external stimulation. For this reason the

child should be observed in an appropriate recovery facility for at least one hour prior to

discharge.

• Specific agonists or reversal agents must be available whenever opioid analgesics or

benzodiazepines are administered prior to a procedure (Table 15). Before or concomitantly with

pharmacologic reversal, patients who become hypoxemic or apneic during the procedure

should: 1) be encouraged or stimulated to breathe deeply; 2) receive positive pressure

ventilation if spontaneous ventilation is inadequate; and 3) receive supplemental oxygen. After

reversal, patients should be observed long enough to ensure that cardiorespiratory depression

does not recur (American Society of Anesthesiologists, 1996).

It is always important to maximize the intervention for the first procedure so that anticipatory

anxiety does not develop. The use of deep sedation or general anesthesia for initial procedures is

one approach which can assure that a patient and family do not have an initial traumatic experience.

For some children pharmacologic treatment may diminish their sense of control and they may feel

helpless and ineffective. Treatment should be individualized to the needs of the patient. The goals

of procedure pain management are to make the procedure as nonthreatening and comfortable as

possible.

VII. Nonpharmacologic Pain Interventions

Nonpharmacologic interventions in the management of pain have been found to be highly

effective for some children and for some procedures. These techniques are easy to learn and should

be used when possible to give the child some control in the management of pain. The examples

given for distraction, muscle relaxation, and guided imagery are easy techniques to learn and can be

used with young children. Additional interventions requiring specialized training include

therapeutic touch and accupressure. However, nonpharmacologic interventions are an adjunct to,

not a substitute, for pharmacological interventions.

Distraction

Distraction is used to focus the child’s attention away from the pain. For children, simple

distraction techniques can be very effective in decreasing pain. Simple measures such as looking at

books, blowing bubbles, and counting are favorite distraction techniques for children. Touch can

be an important distraction technique by stroking, patting and rocking infants as well as children

who are in distress.

Deep breathing is the easiest technique to use with young children. The child is

instructed to take a deep breath through the nose and blow it out through the mouth. Making a

conscious effort to count the child’s respirations focuses attention on the breathing. For school age

children, asking them to hold their breath during a painful procedure transfers their focus to their

breathing and not on the procedure. Asking children to “blow away their pain” has also been

discussed as an effective distraction tool (French, Painter and Coury, 1994).

Parents should be taught distraction measures and encouraged to hold their children for

comfort as much as possible (Table 16). Parent coaching gives them a way to participate in

decreasing their child’s pain and also may provide some benefit in decreasing parent anxiety and

worry.

Table 16. Distraction Techniques in Children Age Methods 0-2 years Touching, stroking, patting, rocking, playing music, using mobiles over the crib

2-4 years Puppet play, storytelling, reading books, breathing, blowing bubbles

4-6 years Breathing, storytelling, puppet play, talking about favorite places, TV shows, activities

6-11 years Music, breathing, counting, eye fixation, thumb squeezing, talking about favorite places, activities on TV shows, humor

Muscle Relaxation

Muscle relaxation is used to decrease mental and physical tension. It is used most

effectively in older children and adolescents because it involves the relaxation of voluntary skeletal

muscles. Slowly each muscle is tensed and then relaxed in a systematic way. Attention is placed

on breathing which causes the individual to be aware of the feelings of tension and relaxation.

Once breathing is under control, attention is focused on the muscles to promote progressive

relaxation. This technique is useful prior to an anxiety producing procedure. Conscious awareness

of the tension creates a more relaxed state, enabling the procedure to be completed more easily.

The following exercise can be used with most children over 5 years of age.

Muscle Relaxation exercise:

Make yourself as comfortable as possible. Move around in your chair or bed until you feel good. Close your eyes when you are ready. Take a deep breath through your nose and breathe it our slowly. Breathe again in and out slowly. Now focus on your hand, make a tight fist and hold it, hold it, now let it relax. Focus your attention on the muscles of your arm, push down your elbow against the arm of the chair or onto the bed, hold it, hold it, now relax your arm. Let’s begin relaxing the muscles of our head and neck. Lift your eyebrows up as high as possible, hold those muscles tight, hold them, now relax and let them go. Squint your eyes and wrinkle your nose, hold those muscles tight, hold them, now relax and let them go. Bite your teeth together and make a smile, hold those muscles tight, hold them, now relax and let them go. Pull your chin down toward your chest, hold it tight, hold it, now relax and let it go. Take a deep breath, hold it, hold it, pull your shoulders back, now relax and let it go. Pull your stomach in and try to hold it, hold it tight, now relax those muscles and let them go. Lift your leg and hold it out straight, hold it, hold it, now relax and let it rest again on the floor or bed. Left the other leg and hold it out straight, hold it, now relax and let it rest again on the floor or bed. Point your toes toward the ceiling, hold them tight, keep them pointed, now relax them, let them go. Take another deep breath through your nose and let it our slowly through you mouth, breathe in again slowly and let it our through your mouth. Notice how relaxed your muscles feel.

Guided Imagery

Guided imagery engages the child by focusing on a pleasant activity, providing distraction

from the pain, or changing the perception of the painful experience. Imagery is used to give the

child the opportunity to imagine being in a more pleasant situation (Table 17). Effective use of

imagery involves all of the child’s senses. When imagining a favorite place the child is asked to

feel the warmth all around, see the colors, smell the odors, and hear the sounds. This helps the child

create a clear scene in their mind. It is important to stress that every child needs a favorite place to

go that is safe. This safe place provides a means of escape. Children often like to imagine they are

watching a favorite TV show or movie. The child can be involved in this type of imagery by asking

the child to discuss what is happening on the TV show like a cartoon. The child can sometimes

imagine being a particular character in the cartoon. The following is an exercise that can be used

with school age children and adolescents.

Guided Imagery Exercise:

Make yourself as comfortable as possible. Move around in your chair or bed. Take a deep breath through your nose and breathe it out slowly. I am going to count and with each number you will notice yourself becoming more comfortable. 12, breathing softly, 11-10-9-8, you can close your eyes if you wish. You may want to imagine in your mind a place that is special to you. It may be at the seashore, by a river, in the mountains. There may be other people there with you, or you might want to be by yourself. 7-6-5-4, you can enjoy this special place and know that your mind will remember it when you need to return. 3-2-1, your breathing is now slow and easy. The muscles of your face are relaxed. Let yourself see, feel, and hear the surroundings of that special place. It is yours. (Pause a few minutes and let them enjoy that special place). When you are ready to return from that special place all your own, you will become more aware of my voice, aware of the light in the room. You may want to stretch your muscles, take a deep breath. You can open your eyes when you are ready.

Table 17. Favorite Imagery Scenes for Children Visual Imagery

Favorite places Animals Flower gardens TV or movies Favorite room Favorite sport

Auditory Imagery Conversations with significant others Favorite song Playing a musical instrument Listening to music Environmental sounds (waves, etc.)

Movement Imagery Flying Swimming Skating Amusement rides Any activity

Comfort Measures

Comfort measures can be a useful treatment option for reducing pain. Comfort measures

can be used as a distraction to help to relieve the anxieties and fears associated with painful

procedures. These measures generally allow the child to feel more relaxed and at ease. Various

comfort measures that can be useful to children with cancer are discussed in Table 18.

Table 18. Comfort Measures

Comfort Measure Description

Quiet presence Sitting quietly and displaying a sense of calmness. Massage Includes stroking, rubbing or deep manipulation of muscles. Music Can help to provide the child with a familiar environment;

children often come to the hospital or hospice with their own music.

Heat Warm compress or use of a heating pad, to the painful site (moist or dry heat).

Cold/Ice Cold compress or ice pack. Precaution: assure ice pack is wrapped allowing comfortable sensation of cold without damaging the skin by freezing tissue. Limit ice application to 10 minutes, then rotate site. If skin becomes blanched, discontinue cold treatment.

Baths Warm soak; can include whirlpool/jacuzzi. Vibration Over the counter massage devise. May be used to stimulate

skin and muscle tissue. Menthol Product (e.g., Ben-Gay)

Apply to skin, however caution must be used to avoid areas of open wounds or irritated skin. Product selection is important as some contain salicylates which may be contraindicated in some patients.

VIII. Special Considerations for The Dying Child

When a child is diagnosed with cancer there is a strong possibility that cure can be achieved.

Options for cure and goals of treatment are outlined with the child and family, and the child is

placed on the most up-to-date treatment protocols available. The health care team monitors

treatment response frequently and assesses for side effects.

For the child and family who do not achieve cure, it is imperative that they receive the same

level of monitoring and assessment of pain and discomfort throughout the terminal phase of the

illness. When the goal of care shifts from a curative intent, to palliation of symptoms and support

through the dying process, health care professionals should inform parents of the options available

for managing pain and other symptoms. Families should be reassured that continued attentive care

and support will be provided. The goal of care becomes freedom from pain and discomfort and

enhancement of the quality of the time remaining to the child and family.

The majority of children with cancer who are terminally ill will require pain relief. Children

with solid tumors often experience metastasis throughout the body and may present with mixed

etiologies (e.g., bone, nerve, visceral) for their pain. These patients may require a combination of

opioids, adjuvants, and invasive therapies to provide adequate pain relief. Children with

hematologic malignancies often experience rapid onset of pain due to marrow infiltration; however,

they are usually managed very successfully on a combination of opioids and adjuvants. Pain in

terminally ill children not only varies with the degree and location of physical damage to tissues but

also by the psychological, social, and cultural factors unique to each child.

Goals of Pain Management in Terminally Ill Children

● The child can sleep undisturbed by pain.

● Side effects from pain medications will be prevented or minimized.

● The child is pain-free when at rest.

● The child can move about or be handled without discomfort.

● The family is educated regarding the pain treatment plan.

● The family is involved in choosing the most effective and appropriate pain management for the

child.

● The family is able to identify increasing pain and provide analgesics to relieve the pain.

Principles for managing pain in terminally ill children

● Consider the concept of complete pain control at all times and conduct a thorough but rapid

assessment of the pain.

● Titrate medications as needed.

● Avoid unnecessary delay in treating the pain, especially if it is severe.

● Follow the WHO analgesic stepladder and utilize pain management interventions appropriate to

the level of pain reported by the child.

● Consider adjuvant therapy at all stages. These drugs have little or no intrinsic analgesic activity

but produce useful pain relief either alone or as an adjuvant to standard analgesic drugs. These

include corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and anxiolytics

(Table 9).

● Give drugs by the least traumatic route available. If a young child refuses oral medications and

administration is traumatic for the parent and child, consider alternative routes such as dermal,

subcutaneous or intravenous infusion to decrease the distress on the child and family.

● Use appropriate conversions when changing route.

● Use around the clock dosing to provide consistent pain relief. Provide extra doses for the

management of escalating or breakthrough pain. PRN doses are only useful for breakthrough

pain, not as the primary management.

● Frequently reassess the child’s pain, particularly after adjusting dosages or adding additional

drugs. If pain is severe, reassess every 30 minutes and continue to modify doses and drugs until

pain relief is achieved. Seek consultation with other pediatric specialties or hospice and

palliative care professionals in complex pain presentations.

● Anticipate side effects associated with analgesic therapy and treat them prophylactically when

possible. Manage any distressing symptoms aggressively as they occur.

Appendix A: Translations for “pain”

Language Translation

Spanish Dolor

French Douleur

German Schmerz

Italian Dolore

Vietnamese Đau

Chinese Tong

Appendix B: Additional Behavioral Assessment Scales

Tools and Authors/ Ages of Use Reliability and Validity Objective Pain Score (OPS) (Hannallah and others, 1987)

Ages of use: 4 months–18 years

No testing in original publication Later tested by original authors 1988–concurrent validity with Linear Analogue Pain Scale, Spearman’s r = 0.721

with scores ∞ 6 and 0.419 with scores < 6 1991–interrater agreement, coefficient alpha = 0.986 for one rater and 0.983 for

the other 1991–concurrent validity with CHEOPS, Pearson correlation coefficient = 0.88

and 0.94

Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS)

(McGrath and others, 1985) Ages of use: 1–5 years

Interrater reliability = 90%–99.5% Internal correlation = significant correlations between pairs of items Concurrent validity between CHEOPS and VAS = 91; between individual and

total scores of CHEOPS and VAS = 0.50–0.86 Construct validity with preanalgesia and postanalgesia scores = 9.9 – 6.33

Nurses Assessment of Pain Inventory (NAPI)

(Stevens, 1990) Ages of use: newborn–16 years

Not tested by original author. Later tested by Joyce and others (1994). Interrater agreement: weighted kappa 0.37–0.80 Discriminant validity: statistically significant differences between preanalgesia

and postanalgesia scores ( p < .0001) Reliability: Cronbach’s alpha = 0.35–0.69

Behavioral Pain Score (BPS) (Robieux and others, 1991)

Ages of use: 3–36 months

Original article stated, “reliability of the BAS and BPS scores was tested by a k test”; no further testing of reliability or validity was mentioned

Modified Behavioral Pain Scale (MBPS)

(Taddio and others, 1995) Ages of use: 4–6 months

Concurrent validity between MBPS and VAS scores = correlation coefficient 0.68 (p < 0.001) and 0.74 (p < 0.001)

Construct validity using prevaccination and postvaccination scores with EMLA vs. placebo: significantly lower scores with EMLA (p < 0.01)

Internal consistency of items = significant correlations between items Interrater agreement: ICC = 0.95, p < 0.001 Test–retest reliability: r = 0.95, p < 0.001

Riley Infant Pain Scale (RIPS) (Schade and others, 1996)

Ages of use: <36 months and children with cerebral palsy

Interrater agreement using Intraclass Correlation Coefficient = 0.53–0.83, p < 0.0001

Discriminant validity using Mann–Whitney U test with preanalgesia and postanalgesia scores = statistically significant (p < 0.001)

Sensitivity = 0.31–0.23 Specificity = 0.86–0.90

FLACC Postoperative Pain Tool (Merkel and others, 1997)

Ages of use: 2 months–7 years

Interrater reliability using two–way cross tabulations and kappa statistics (r[87] = 0.94; p < 0.001) and kappa values above 0.50 for each category

Validity using ANOVA for repeated measures to compare FLACC scores before and after analgesia; preanalgesia FLACC scores were significantly higher than postanalgesia scores at 10, 30, and 60 minutes (p < 0.001 for each time)

Correlation coefficients used to compare FLACC pain scores and OPS pain scores; significant positive correlation between FLACC and OPS scores (r = 0.80; p < 0.001); positive correlation also found between FLACC scores and nurses’ global ratings of pain (r[47] = 0.41; p < 0.005)

Appendix C: Spanish Translation for FACES Pain Rating Scales for Children

FACES Pain Rating Scale (Whaley and Wong, 1999, with permission)

0 No Hurt

1 Hurts

Little Bit

2 Hurts

Little More

3 Hurts

Even More

4 Hurts

Whole Lot

5 Hurts Worst

FACES Scale From Nursing Care of Infants and Children, 6th ed., (p 2040), by DL Wong and others, 1999. St. Louis: Mosby. Copyright 1999, Mosby. Reprinted with permission. Expliquele a la persona que cada cara representa una persona que se siente feliz perque no tiene dolor o triste perque siente un poco o mucho dolo. Cara 0 se siente muy feliz perque notiene dolor. Cara 1 tiene un poco de dolor. Cara 2 tiene un poquito más de dolor. Cara 3 tiene más dolor. Cara 4tiene mucho dolor. Cara 5 tiene el dolor más fuerte que usted pueda imaginar, aunque usted no tiene que estar llorando para sentirse asi de mal. Pidale a la persona que escoja la cara mejor descibe su proprio dolor. Esta escala se puede usar con personas de tres años de edad más.

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