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 Childrens Cancer Center Texas Childrens Hospital, Houston, Texas Patrick Barrera, BS Project Coordinator Texas Childrens Cancer Center Texas Childrens Hospital, Houston, Texas Melody Brown, MS, RN, CPON Coordinator, Childrens Hospice Services The Hospice at the Texas Medical Center, Houston, Texas Sarah J. Bottomley, MN, RN, CPNP, CPON Pediatric Nurse Practitioner Texas Childrens Cancer Center Texas Childrens Hospital, Houston, Texas Jill Brace ONeill, MS, RN-CS, PNP, CPON Pediatric Nurse Practitioner Texas Childrens Cancer Center Texas Childrens Hospital, Houston, Texas

Texas Childrens Hospital

Baylor College of Medicine

REVIEWERS: Donna Wong, PhD, RN, PNP, CPN, FAAN Nurse Consultant, The Childrens 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 Childrens Cancer Center, Texas Childrens Hospital, Houston, Texas Douglas Strother, MD Assistant Professor of Pediatrics, Baylor College of Medicine, Houston, Texas Texas Childrens Cancer Center, Texas Childrens Hospital, Houston, Texas Edith M. Eby, PharmD Clinical Pharmacy Specialist, Hematology/Oncology Texas Childrens Hospital, Houston, Texas Nancy E. Kline, PhD, RN, CPNP Assistant Professor of Pediatrics, Baylor College of Medicine Pediatric Oncology Nurse Practitioner Texas Childrens Cancer Center Texas Childrens 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 Childrens Medical Center of Dallas Dallas, Texas Marge Brown, RN Driscoll Childrens Hospital, Childrens Medical Center of South TX. Corpus Christi, Texas Melody Brown, MS, RN, CPON Coordinator, Childrens 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 Childrens Hospital Lubbock, Texas Janine Primomo, MSN, RN Department Head Pediatric Hematology Oncology Santa Rosa Childrens Hospital San Antonio, Texas Kathleen M. White, MSN, RN, CPNP Cook Childrens Medical Center Fort Worth, Texas

APON Clinical Practice Committee Reviewers:

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

Pain Management In Children With Cancer:

Content Outline
Introduction I. II. III. IV. V. VI. VII. Physiology of Pain Etiology of Cancer Pain Barriers to Effective Pain Management Pain Assessment Pharmacologic Pain Management Procedure Related Pain Nonpharmacologic Pain Management pp 8 pp 9-10 pp 11-13 pp 14-16 pp 17-23 pp 24-44 pp 45-49 pp 50-54 pp 55-56

VIII. Special Considerations For The Dying Child IX. X. Appendices 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 childs 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
B. Visceral Pain

II.

Neuropathic Pain
D. Peripherally Generated Pain

A. Somatic Pain I.

C. Centrally Generated Pain II.

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

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

2.

2.

B. Peripherally Generated Pain 1.

2.

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

Bone -Skull -Vertebrae -Pelvis/femur

Clinical Presentation
-Aching to sharp, severe pain generally more

Causes
-Infiltration of bone -Skeletal metastases - irritation and stretching of pain receptors in the periosteum and endosteum. -Prostaglandins released from bone destruction.

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

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

-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). -Obstruction bowel, urinary tract, biliary tract -Mucosal ulceration -Metabolic alteration -Nociceptor activation, generally from distention or inflammation of visceral organs

Visceral -Soft tissue -Tumors of the bowel -Retroperitoneum

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

-Post-LP headaches -Radiation dermatitis -Post-surgical

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. Childrens 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-weekold 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 drugs 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. Childrens 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: Childrens behavior reflects their pain intensity. Fact: Children are unique in their ways of coping. Childrens 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) 4)

Fear that pain is a sign that the disease is worsening. 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. There is often a lack of a comprehensive approach to pain assessment. Healthcare providers may underestimate the intensity of the childs pain. 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. Health care providers frequently have limited knowledge regarding state of the art pain management. There is often reluctance by nurses or family members to administer medications due to fear of addiction, over medication, and/or side effects.

2) 3) 4)

5)

6)

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 childs 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 patients 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
Tell me what pain is. Tell me about the hurt you have had before. Do you tell others when you hurt? If yes, who? What do you do for yourself when you are hurting? What do you want others to do for you when you hurt? What dont you want others to do for you when you hurt? What helps the most to take your hurt away? Is there anything special that you want me to know about you when you hurt? (If yes, have child describe.)

Parent Form
What word(s) does your child use in regard to pain? Describe the pain experiences your child has had before. Does your child tell you or others when he/she is hurting? How do you know when your child is in pain? How does your child usually react to pain? What do you do for your child when he/she is hurting? What does your child do for him/herself when he/she is hurting? What works best to decrease or take away your childs 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 121135. Copyright 1994 Hemisphere Pub. Corp. Adapted with permission.

Table 4. Pain Rating Scales for Children

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

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

Recommended Age
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 horizontally or vertically. 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.

0 No Pain

2. Physical Examination Performing a complete physical examination is vital to a thorough assessment of a patients 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 selfreport 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 childs 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
Face

0
No particular expression or smile Normal position or relaxed Lying quietly, normal position, moves easily No cry (awake or asleep) Content, relaxed

1
Occasional grimace or frown, withdrawn, disinterested Uneasy, restless, tense Squirming, shifting back and forth, tense Moans or whimpers; occasional complaint Reassured by occasional touching, hugging or being talked to, distractible

2
Frequent to constant quivering chin, clenched jaw Kicking, or legs drawn up Arched, rigid or jerking Crying steadily, screams or sobs, frequent complaints Difficult to console or comfort

Legs Activity Cry Consolability

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.

Behavior/ Category
Facial Body Movement Sleep

Riley Infant Pain Scale Assessment Tool 0

Neutral/smiling Calm, relaxed

1
Frowning/grimacing Restless/fidgeting

2
Clenched teeth Moderate agitation or moderate mobility Sleeps intermittently (sleep/awake) Pain crying Not easy to console Cries out when moved/touched

3
Full cry expression Thrashing, flailing, incessant agitation or strong voluntary immobility Sleeping for prolonged periods of time interrupted by jerky movements or unable to sleep Screaming, high-pitched cry Inconsolable High-pitched cry or scream when touched or moved

Sleeping quietly with easy respirations No cry Neutral Moves easily

Restless while asleep

Verbal/vocal Consolability Response to movement/ Touch

Whimpering, complaining Easy to console Winces when touched/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 Infants Expressions of Pain May: l Exhibit body rigidity or thrashing, may include arching l Exhibit facial expression of pain (brows lowered and drawn together, eyes tightly closed, mouth open and squarish) l Cry intensely/loudly l Be inconsolable l Draw knees to chest l Exhibit hypersensitivity or irritability l Have poor oral intake l Be unable to sleep 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 May: l Verbalize intensity of pain l See pain as punishment l Exhibit thrashing of arms and legs l Attempt to push stimulus away before it is applied l Be uncooperative l Need physical restraint l Cling to parent, nurse, or significant other l Request emotional support (e.g. hugs, kisses) l Understand that there can be secondary gains associated with pain l Be unable to sleep May: l Verbalize pain l Use an objective measurement of pain l Be influenced by cultural beliefs l Experience nightmares related to pain l Exhibit stalling behaviors (e.g., Wait a minute or Im not ready) l Have muscular rigidity such as clenched fists, white knuckles, gritted teeth, contracted limbs, body stiffness, closed eyes, or wrinkled forehead l Include all behaviors of preschoolers/young children l Be unable to sleep May: l Localize and verbalize pain l Deny pain in presence of peers l Have changes in sleep patterns or appetite l Be influenced by cultural beliefs l Exhibit muscle tension and body control l Display regressive behavior in presence of family l Be unable to sleep
l l l l l

Toddlers

Preschoolers/Young Children

School-Age Children

Adolescents

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 patients 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 childs 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 patients 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 childs 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 antiinflammatory 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 childs 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 Aspirin Ibuprofen Choline magnesium trisalicylate Diclofenac sodium Naproxen Naproxen sodium Ketorolac 10 to 15 mg/kg/dose q 4 hr PO to a max of 650 mg/dose 10 to 15 mg/kg/dose q 6 to 8 hr PO to a max of 650 mg/dose 10 mg/kg/dose to a max single dose of 800 mg q 6 to 8 hr PO 7.5 to 25 mg/kg/dose bid-tid; max single dose of 1500 mg PO 1 to 1.5 mg/kg/dose to a max single dose of 75 mg q 8 to 12 hr PO 5 to 7.5 mg/kg/dose to a max of 500 mg/dose q 12 hr PO Same as Naproxen 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 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

Celecoxib (Cox-2 inhibitor) Rofecoxib (Cox-2 inhibitor)

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, HockenberryEaton, 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. Crosstolerance 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 Codeine Acetaminophen and Codeine Oral Starting Doses 0.5 to 1 mg/kg q 4 to 6 hr; max: 60 mg/dose 0.5 to 1.0 mg/kg/dose of codeine q 4 to 6 hr; max: 2 tablets/dose; 15 mL/dose Dosage Forms Tablet, as sulfate: 30 mg Liquid: 3 mg/mL 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 Starting Doses IV N/A N/A IV to PO N/A N/A

Drug Hydrocodone and Acetaminophen

Oral Starting Doses 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 Instant release: 0.05 to 0.15 mg/kg/dose up to 5 mg/dose q 4 to 6 hr Sustained release: for patients taking >20 mg/day of oxycodone can administer 10 mg q 12 hr 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 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

Dosage Forms Tablet: hydrocodone 5 mg and acetaminophen 500 mg Oral solution at: 0.5 mg hydrocodone and 33.4 mg/mL acetaminophen

Starting Doses IV N/A

IV to PO N/A

Oxycodone

Instant release: 5 mg Sustained release: 10 mg, 20 mg, 40 mg, 80 mg

N/A

N/A

Morphine

Fentanyl

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

0.1 mg/kg/ dose 0.1 to 0.2 mg/kg/dose q 2 to 4 hr; max: 15 mg/dose 1 to 2 mcg/kg/dose; max: 50 mcg/ dose Continuous IV infusion: 1 mcg/kg/hr

10 mg IV = 30 to 60 mg PO N/A

Patch: 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, 100mcg/hr Injection: 50 mcg/mL

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

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

Suppository: 3 mg 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 Amitriptyline Dosage 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 Indication ANTIDEPRESSANTS Continuous neuropathic pain with burning, aching, dysthesia with insomnia Provides analgesia by blocking reuptake 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 Comments

Nortriptyline

0.2 to 1.0 mg/kg PO a.m. or bid Neuropathic pain Titrate up by 0.5 mg q 5 to 7 days as above without Max: 25 mg/dose insomnia ANTICONVULSANTS 5 mg/kg PO at bedtime Increase to bid on day 2, tid on day 3 Max: 300 mg/day <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 Neuropathic pain Mechanism of action unknown. Side effects include sedation, ataxia, nystagmus, dizziness

Gabapentin

Carbamazepine

Sharp, lancinating Similar analgesic effect as neuropathic amitriptyline pain Monitor blood levels for toxicity Peripheral only neuropathies Side effects include decreased blood Phantom limb counts, ataxia, and GI irritation pain

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 Dose dependent on clinical situation; Pain from higher bolus doses in cord compression, increased then lower daily dose. Try to wean to intercranial NSAIDs if pain allows pressure Cerebral edema: 1 to 2 mg/kg load then 1 Bony metastasis to 1.5 mg/kg/day divided every 6 hr; Spinal/nerve max: 4 mg/dose compression Anti-inflammatory: 0.08 to 0.3 mg/kg/day divided every 6 to 12 hr OTHERS 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 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

Dexamethasone

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 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 longterm 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
Constipation

Adjuvant Drugs
Senna and docusate sodium: Tablet: 2 to 6 years Start: 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 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 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

Nonpharmacologic Techniques
Increase water intake Prune juice, bran cereal, vegetables

Sedation

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

Nausea/Vomiting

Imagery, relaxation Deep, slow breathing

Side Effect
Pruritus

Adjuvant Drugs
be very sedating 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 Hold dose of opioid Reduce subsequent doses by 25% 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 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 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

Nonpharmacologic Techniques
Oatmeal baths, good hygiene Exclude other causes of itching Change opioids

Respiratory depression: Mildmoderate Respiratory depression: Severe

Arouse gently, give O2, encourage to deep breath O2, bag and mask if indicated

Dysphoria/confusion /hallucinations

Rule out other physiologic causes

Urinary retention

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 childs 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 patients 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 Loading dose Background infusion (basal rate) Interval dose Lockout Four-hour maximum Purpose Obtain immediate pain control To maintain continuous pain relief Initial Dose Recommendations 0.05 to 0.1 mg/kg; max: 10 mg 0.01 to 0.02 mg/kg/hr

A bolus interval dose will allow the 0.015 to 0.025 mg/kg patient to titrate his/her own pain control To prevent overdose in an opioid nave 6 to 15 minutes patients To avoid overdose in an opioid nave 0.25 to 0.35 mg/kg patient. Assess q hr to determine adequate pain management and adjust dose as necessary (McCaffery, 1999)

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 To PO 10 mg IV = X mg IV morphine = 60 mg PO 90 mg PO morphine/24 hr 10 x 90 = 900 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 = 1.5 mg IV hydromorphone 15 mg IV morphine X mg IV hydromorphone (1.5 x 15) 10 = X

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 24 = 0.1 mg/hr IV hydromorphone

Table 12. Equianalgesic Conversion Table

Drug Onset (min) Peak(h) 1 (h) EquianalgesicDoses IV/IM Codeine Fentanyl Hydrocodone Hydromorphone Methadone Morphine Oxycodone, P.O. Oxymorphone 10-30 7-8 ND 15-30 30-60 15-60 15-30 5-10 0.5-1 ND ND 0.5-1 0.5-1 0.5-1 1 0.5-1 3 1.5-6 3.3-4.5 2-3 15-30 1.5-2 ND ND (mg) 120 0.1 ND 1.5 10 10 NA 1 Oral (mg) 200 NA ND 7.5 20 60 30 10#

From: Texas Childrens 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)
45-134 135-224 225-314 315-404 405-494 495-584 585-674 675-764 765-854 855-944 945-1034 1035-1124
1

IM 24-Hr Morphine (mg/day)

8-22 23-37 38-52 53-67 68-82 83-97 98-112 113-127 128-142 143-157 158-172 173-187

Duragesic Dose (g/hr)

25 50 75 100 125 150 175 200 225 250 275 300

The 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 persons 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. 2. 3. 4. 5. 6. 7. Prepare the child and parent(s) with specific interventions. Provide maximum treatment of pain and anxiety for the initial procedure to reduce the development of subsequent anticipatory anxiety symptoms. Provide adequate knowledge of behavioral and pharmacologic treatment of acute pain and anxiety by medical staff responsible for procedures. Use appropriate monitoring and resuscitative equipment in the procedure room when using sedation. Assure adequate mechanical skill in individuals who plan to perform pediatric procedures. Provide ongoing evaluation of the child to assess efficacy of treatment for pain and anxiety. 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 childs 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 patients 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 patients 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 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 Fentanyl: A Narcotic analgesic Onset: 1 to 5 minutes Peak Effect: (no data available) Half Life: 1.5 to 6 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 Dosing Side-Effects Reversal Agents

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) 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) None

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

UNCONSCIOUS SEDATION: Propofol: A General anesthetic IV: 1 to 2 mg/kg followed by 75 to Onset: within 30 100 mcg/kg/minute seconds (Only with qualified anesthesia

Pain on injection, involuntary movements, hypotension, apnea

Drug Peak Effects: 3 to 10 minutes Half Life: 3 compartment model: initial: 2 to 8 minutes 2nd Distribution: 40 minutes terminal: 200 minutes Ketamine: A General anesthetic Onset: 30 seconds with IV administration; PO 20 to 45 minutes Peak Effects: 5 minutes Half Life: unknown

Dosing personnel available)

Side-Effects

Reversal Agents

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 childs 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 childs 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 childs pain and also may provide some benefit in decreasing parent anxiety and worry.

Table 16. Distraction Techniques in Children Age

0-2 years 2-4 years 4-6 years 6-11 years

Methods
Touching, stroking, patting, rocking, playing music, using mobiles over the crib Puppet play, storytelling, reading books, breathing, blowing bubbles Breathing, storytelling, puppet play, talking about favorite places, TV shows, activities 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. Lets 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 childs 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 Quiet presence Massage Music Heat Cold/Ice Description Sitting quietly and displaying a sense of calmness. Includes stroking, rubbing or deep manipulation of muscles. Can help to provide the child with a familiar environment; children often come to the hospital or hospice with their own music. Warm compress or use of a heating pad, to the painful site (moist or dry heat). 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. Warm soak; can include whirlpool/jacuzzi. Over the counter massage devise. May be used to stimulate skin and muscle tissue. 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.

Baths Vibration Menthol Product (e.g., Ben-Gay)

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 childs 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 French German Italian Vietnamese Chinese

Dolor Douleur Schmerz Dolore au Tong

Appendix B: Additional Behavioral Assessment Scales Tools and Authors/ Ages of Use
Objective Pain Score (OPS) (Hannallah and others, 1987) Ages of use: 4 months18 years

Reliability and Validity

No testing in original publication Later tested by original authors 1988concurrent validity with Linear Analogue Pain Scale, Spearmans r = 0.721 with scores 6 and 0.419 with scores < 6 1991interrater agreement, coefficient alpha = 0.986 for one rater and 0.983 for the other 1991concurrent validity with CHEOPS, Pearson correlation coefficient = 0.88 and 0.94 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 = 0.500.86 Construct validity with preanalgesia and postanalgesia scores = 9.9 6.33 Not tested by original author. Later tested by Joyce and others (1994). Interrater agreement: weighted kappa 0.370.80 Discriminant validity: statistically significant differences between preanalgesia and postanalgesia scores ( p < .0001) Reliability: Cronbachs alpha = 0.350.69 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 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 Testretest reliability: r = 0.95, p < 0.001 Interrater agreement using Intraclass Correlation Coefficient = 0.530.83, p < 0.0001 Discriminant validity using MannWhitney U test with preanalgesia and postanalgesia scores = statistically significant (p < 0.001) Sensitivity = 0.310.23 Specificity = 0.860.90 Interrater reliability using twoway 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)

Childrens Hospital of Eastern Ontario Pain Scale (CHEOPS) (McGrath and others, 1985) Ages of use: 15 years Nurses Assessment of Pain Inventory (NAPI) (Stevens, 1990) Ages of use: newborn16 years Behavioral Pain Score (BPS) (Robieux and others, 1991) Ages of use: 336 months Modified Behavioral Pain Scale (MBPS) (Taddio and others, 1995) Ages of use: 46 months

Riley Infant Pain Scale (RIPS) (Schade and others, 1996) Ages of use: <36 months and children with cerebral palsy FLACC Postoperative Pain Tool (Merkel and others, 1997) Ages of use: 2 months7 years

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 ms de dolor. Cara 3 tiene ms dolor. Cara 4tiene mucho dolor. Cara 5 tiene el dolor ms 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 aos de edad ms.

References:
AAP American Academy of Pediatrics, Committee on Drugs (1992). Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics, 89(6), 1110-1115. APS American Pain Society (1999). Principles of analgesic use in the treatment of acute pain and cancer pain, (4th ed.). Glenview, IL: American Pain Society. American Society of Anesthesiologists (1996). Practice Guidelines for Sedation and Analgesia by Non-Anesthesiologists. A Report by the American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Anesthesiology, 84, 459-471. Anand KJ (1998). Clinical importance of pain and stress in preterm neonates. Biol Neonate, 73(1), 1-9. Baker CM and Wong DL (1987). QUEST: a process of pain assessment in children. Orthop Nurs 6(1),11-21. Beyer JE, McGrath PJ and Berde CB (1990). Discordance between self-report and behavioral pain measures in children aged 3-7 years after surgery. J Pain Symptom Manage 5(6), 350-356. Broome ME, Rehwaldt M and Fogg L (1998). Relationships between cognitive behavioral techniques, temperament, observed distress, and pain reports in children and adolescents during lumbar puncture. J Pediatr Nurs 13(1), 48-54. Broome ME, Bates TA, Lillis PP and McGahee TW (1990). Childrens medical fears, coping behaviors, and pain perceptions during a lumbar puncture. Onc Nurs Forum 17(3), 361-367. Collins JJ and Berde CB (1997). Management of cancer pain in children. In PA Pizzo and DG Poplack (Eds), Principles and Practice of Pediatric Oncology, 3rd ed, (pp. 1183-1199). Philadelphia: Lippincott-Raven. Favaloro R and Touzel B (1990). A comparison of adolescents and nurses postoperative pain ratings and perceptions. Pediatr Nurs, 16(4), 414-424.

French GM, Painter EC, and Coury DL (1994). Blowing away shot pain: A technique for pain management during immunization. Pediatrics, 93(3), 384-388. Foley KM (1996). Controlling the pain of cancer. Sci Am 275(3),164-165. Hertzka RE, Gauntlett IS, Fisher DM and Spellman MJ (1989). Fentanyl-induced ventilatory depression: effects of age. Anesthesiology 70(2), 213-218. Jacox A, Carr DB, Payne R and others (1994). Management of Cancer Pain: Adults Quick Reference Guide, (No 9, AHCPR Publication No 94-0593). Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Department of Health and Human Services. Kart T, Christrup LL and Rasmussen M (1997). Recommended use of morphine in neonates, infants and children based on a literature review: Part 2Clinical use. Paediatr Anaesth 7(2), 93-101. Leahy S, Hockenberry-Eaton M and Sigler-Price K (1994). Clinical management of pain in children with cancer: selected approaches and innovative strategies. Cancer Practice 2(1), 37-45. Martin G (1998). Experience talks: How weve managed pain and symptoms in our pediatric hospice patients. Hospice, 9(1), 21-23. McCaffery M and Pasero C (1999). Pain: A Clinical Manual, 2nd ed. St. Louis: Mosby. McGrath PA (1996). Development of the World Health Organization guidelines on cancer pain relief and palliative care in children, J Pain Symptom Manage 12(2), 87-92. Micromedex Healthcare Series: MICROMEDEX Inc, Englewood, Colorado, 1999. Olson G and Berde C (1993). Neuropathic pain in children and adolescents. In NL Schechter, CB Berde and M Yaster (Eds), Pain in Infants, Children, and Adolescents (pp 473-493). Baltimore, MD: Williams & Wilkins.

Physicians Desk Reference, 53rd ed. (1999). Montvale, New Jersey: Medical Economics Company. Sabatino G Quartulli L, Faio S and Ramenghi, LA (1997). Hemodynamic effects of intravenous morphine infusion in ventilated preterm babies. Early Hum Dev 47(3), 263-270. Schecter NL, Berde CB and Yaster M, (Eds). (1993). Pain in Infants, Children, and Adolescents. Baltimore, MD: Williams & Wilkins. Taketomo CK, Hodding, JH and Kraus DM (1998). Pediatric dosage handbook, 4th ed, 1997-1998. Hudson, Ohio: Lexi-Comp. Tesler MD and others (1991). Childrens words for pain. In SG Funk and others, (Eds), Key aspects of comfort: management of pain, fatigue, and nausea. New York: Springer. Texas Childrens Hospital, Pharmacy Department (1999). Drug information and formulary, 5th ed. Hudson, Ohio: Lexi-Comp. Whaley L and Wong DL (1987). Nursing care of infants and children, 3rd ed. St Louis: CV Mosby. Wong DL and Baker C (1988). Pain in children: comparison of assessment scales. Pediatr Nurs 14(1), 9-17. Yaster M and others (1997). Pediatric pain management and sedation handbook. St. Louis: Mosby. Zeltzer LK, Jay SM and Fisher DM (1989). The management of pain associated with pediatric procedures. Pediatr Clin North Am 36(4), 941-964.