Management of Pain

Author: Ayda G. Nambayan, DSN, RN, St. Jude Children’s Research Hospital Content Reviewed by: Nursing Education Department, International Outreach Program, St. Jude Children’s Research Hospital Wren Kennedy, RN, MSN, PNP/O, St. Jude Children’s Research Hospital Cure4Kids Release Date: 1 September 2006

Children of all ages deserve compassionate and effective pain treatment. - World Health Organization

It is a common belief that if a child or adolescent has cancer, he or she must be in pain. Although this statement is not necessarily true, if and when the child or adolescent has pain, concerted efforts should be made to reduce or eliminate the pain whenever possible. As a population group, pediatric patients in general are at risk of undertreatment of pain; undertreatment is due perhaps to several reasons related to age and assessment. Not only should the nurse be mindful of the presence of pain, but also parents should be encouraged to discuss the issue of pain with the health care providers. Studies have shown that anxiety, fear and even phobias can develop as a result of painful experiences long before children can express them.

The goal of pain management is to provide each child or adolescent with the dose of analgesic medication that prevents the recurrence of pain before the next dose is administered; thus, the patient remains pain-free (McGrath, 1996). Health care providers must be educated and provide information to patients and families regarding the appropriate medical use of analgesic agents.

The treatment plan for pain is usually based upon the following factors:  The patient’s age,  The patient’s overall health and medical history, which should include the results of an assessment of the presence, of persistent and breakthrough pain and their effects on function,  The type and extent of the cancer,  A diagnostic evaluation of signs and symptoms associated with common presentations of cancer pain and syndromes,  A patient’s tolerance of specific medications, procedures and therapies,  The parents’ opinions and preferences,  The outcomes of the psychosocial assessment.

Several professional groups (A – 1) have developed recommendations, assessment and management guidelines and treatment algorithms that are designed for clinical use. Module 9 - Document 7 Page 1 of 18 Management of Pain

Although the recommendations (A – 2) are good roadmaps, 2 key principles should be emphasized in planning and implementing strategies of pain management: the regimen should be individualized, and the administration or implementation of the regimen should be optimized.

Individualizing the Regimen

There is not a standard dose of pain medication that will work for all children and adolescents. It is important that the needs of the patient be considered when the dosages of pain medication are determined.

Individualizing the pain treatment plan (A – 3) begins with a comprehensive pain assessment. To date, there are many different formulations of pain medications. Their creative use in a logical manner and according to the specific patient needs is becoming accepted practice. Information gathered during the assessment will help clinicians develop a strategy in which pharmacologic and nonpharmacologic approaches are used to manage pain. For example, instead of the oral route for administration of pain medication, a transdermal route may be used to treat the patient who has mucositis, dislikes swallowing pills or has had bad experiences with the taste of oral medications.

The health care professional should use information gathered during the assessment about the culture and beliefs of the patient and the family. For example, Chinese patients traditionally take medications as a single dose and may not continue taking the medication around the clock if they feel well. They may also be confused by the use of controlled-release pain medications.

The medication dose should be titrated according to the desired effect (the absence of pain with minimal side effects). Because individual patients may respond differently to the same analgesic medications and dose, the amount and dose intervals must be titrated to optimize the balance between analgesia and side effects.

Understanding the unique needs of each child or adolescent is essential in providing appropriate pain interventions. Careful consideration of the patient’s situation provides individualized pain treatment and its associated nursing care – thus, the patient’s quality of life will be improved.

Optimizing Administration

The rule regarding optimization of administration is to provide sufficient analgesic(s) to continuously relieve the pain, if possible. A preventive approach may entail administering analgesic medications (or starting imaging activities) before the pain occurs or increases. To maintain the optimum level of pain relief, analgesic administration should be scheduled to prevent pain recurrence. Examples include giving the pain medication several minutes before a painful procedure such as dressing changes and around-the-clock administration of analgesics if the pain is present most of the day. Another example is using timed- or continuous- release formulations for patients with persistent pain

Another way that clinicians can optimize administration is to be creative with the meaning of “PRN” (as needed) analgesics. Nurses have been taught to administer PRN medications only when a patient requests them; however, current clinical practice guidelines recommend the proactive use of analgesics as around-the-clock rather than PRN medications to prevent pain Module 9 - Document 7 Page 2 of 18 Management of Pain from becoming severe. Thus, PRN analgesics should be given if the pain assessment indicates the need for the analgesic (presence of breakthrough pain), even if the patient has not yet requested it.

Because young children and infants have lower pain thresholds and poor central modulation, they will often require sedation or general anesthesia to undergo procedures (such as bone marrow aspiration) that adults often undergo with minimal or no analgesia. Older children and adolescents may be given opioids or nonopioid analgesics before they undergo such procedures; however, ample time for the analgesic(s) to reach its peak concentration should be allowed before the painful procedures are performed.

Pharmacologic Management of Pain

Effective doses of analgesics (A – 4) should be used to treat pain; the selection of the appropriate analgesic should depend upon its indications for use, side effects, needs of the individual patient, dosing and titration. A good guideline that is commonly used in clinical practice is the World Health Organization (WHO) Analgesic/Pain Ladder (A – 5).

Nonopioid analgesics (A – 6) are a class of pharmacologic agents that can effectively treat mild to moderate pain and are often used in combination with an opioid analgesic to control pain caused by bone metastasis and other types of severe pain. The main types of nonopioid analgesics are as follows:

 acetaminophen (Tylenol®), which is usually the drug of choice for children with mild to moderate pain;  aspirin (ASA), although it is not commonly used in patients with cancer because of its antiplatelet activity;  other nonsteroidal anti-inflammatory drugs, which have analgesic, antipyretic and anti-inflammatory effects, inhibit cyclo-oxygenases 1 and 2 (COX1 and COX2) and prevent synthesis of prostaglandins.

Opioids (A – 7) are a second class of pharmacologic agents used to treat pain. Their mechanism of action depends upon their ability to bind to specific opioid receptors in the central nervous system (CNS). The primary CNS receptors are mu (μ) and kappa (ĸ). Opioids are also capable of altering the perception of and emotional responses to pain because of the wide distribution of the opioid receptors in the CNS. Opioids are classified as agonists, partial agonists and agonist- antagonists.  Agonist opioids bind to the opioid receptors to activate them and stimulate the maximum response mediated by the individual receptors.  Partial agonists bind to the receptors, but their binding produces only a partial response.  Agonist-antagonist opioids cause mixed effects – these compounds act as an agonist at one type of opioid receptor and as a competitive antagonist at another.

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Adjuvant drugs (A – 8), a third class of pharmacologic agent used to treat pain, are medications used in combination with analgesics to enhance pain relief or to treat symptoms that exacerbate pain. In some instances, adjuvant drugs may be used alone to treat specifically identified pain. Medications in this category include the following.  Anticonvulsants, antidepressants, anesthetics and antidysrhythmics are commonly used to treat neuropathic pain and are often used in combination with an opioid.  Antihistamines have analgesic properties as well as anxiolytic and sedative effects, which are often helpful for patients who need to rest.  Corticosteroids are beneficial to the treatment of cancer pain originating in a fairly restricted area such as an intracranial or pelvic region or an area along a nerve root. Corticosteroids suppress the release of prostaglandins; thus, inflammation is inhibited, and subsequently pressure within the confined area or along the nerve is relieved.  Psychostimulants potentiate opioid analgesia and increase alertness or reduce persistent opioid-induced sedation in some patients.  Clonidine (Catapres; Duraclon) is used to treat pain related to reflex sympathetic dystrophy. It is also used in patients who have cancer and are opioid- tolerant or have phantom pain syndrome.  Capsaicin is an alkaloid derived from chili peppers and is formulated into a cream (in Asia, capsaicin is often imbedded in adhesive tapes for transdermal delivery). This drug decreases pain transmission by depleting substance P in nerve fibers. Often the drug is topically applied to relieve muscle aches and other types of localized pain. One common name brand of capsaicin is Zostrix.

Methods of Drug Delivery

Most pain medications are available in oral preparations. The oral route is the preferred route of administration to patients except those who have problems with swallowing because of tumor growth or mucositis and those who have problems with retention (i.e., those who have a problem with excessive vomiting or diarrhea).

Some medications can be given rectally. This route can be used to treat pain in patients with problems such as chemotherapy-induced nausea and vomiting. This route should not be used in patients who are immunocompromised because damage to the rectal mucosa due to drug administration can increase the risk of infection.

Subcutaneous and intramuscular routes of drug delivery should be considered only as a last resort for analgesic administration. Intramuscular injections cause added pain which is unnecessary.

Intravenous delivery provides fast analgesia and should be considered if the patient is unable to tolerate oral or transdermal delivery of medication.

Transdermal delivery is also preferable, but the availability of transdermal analgesics is limited.

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Methods and Concepts of Analgesic Therapy

The Latin phrase “pro re nata” (PRN) means “as needed,” i.e., a drug should be administered only when it is required. Ordinarily, patients or parents request pain medications. PRN administration of analgesics is useful in treating intermittent pain and breakthrough pain and in initiating opioid analgesic therapy to opioid-naive patients.

Around-the-clock (ATC) administration of an analgesic means that the agent is given at specified times within a 24-hour period, regardless of the presence or absence of pain. ATC administration is usually prescribed to treat severe, continuous types of pain such as chronic cancer pain or, at times, immediately during the initial postoperative period. The goal is to maintain a pain rating that is satisfactory to the patient by maintaining a stable blood concentration of the analgesic(s). Drugs commonly administered ATC include controlled- or sustained-release preparations combined with immediate-release analgesics (given in rescue doses) for breakthrough pain.

Patient-controlled analgesia (PCA) (A – 9) is an interactive method of pain management in which the patient self-administers doses of analgesic(s). Although the dosage and dose interval are usually preset by the clinician (lock-out), the patient controls the time that the dose is administered; thus, this method addresses the significant variations in analgesic requirements between individual patients. The lock-out mechanism prevents inadvertent overdose or administration of excessive analgesia. Studies have shown that some of the advantages of PCA include enhancement of self-care abilities, which increases patient empowerment, and, if used as prescribed and intended, PCA can significantly reduce the risk of oversedation.

Proxy patient-controlled analgesia (PPCA) can be used by patients who are cognitively but not physically able to use a PCA device because of neuromuscular limitations, young age or terminal disease. In pediatrics, the proxy is most often the caregiver (either the parents or the nurse). However, complications such as oversedation, respiratory depression and even death have been associated with PPCA. These complications are often the result of well-intentioned efforts by family and caregivers to keep the patient comfortable. Some recommendations to ensure continuing safety include careful patient selection, education of proxy users, appropriate documentation and compliance with institutional guidelines.

Continuous intravenous infusion may be used when other routes and dosing methods have failed to satisfactorily relieve pain. The initial dose (infusion rate) is determined by the current requirements of the pain treatment, and dose adjustments are based on objective and subjective evidence of pain relief and side effects. Before continuous infusion begins, it is necessary to obtain measures of the baseline vital signs for later comparison.

Patients who are on a fixed schedule for pain control (ATC administration of analgesics) may experience intermittent flares of pain (breakthrough pain). These intermittent flares can be effectively managed by breakthrough doses. The requirements for breakthrough doses are used to evaluate pain status and the efficacy of the fixed dosing schedule. Short-acting opioids are often used to treat breakthrough pain because they are easily administered, have a rapid onset of action and are rapidly excreted.

Balanced analgesia is a continuous multimodal approach that is useful in treating continuous pain. This method uses a combination of analgesic regimens; thus, significant side effects due to Module 9 - Document 7 Page 5 of 18 Management of Pain a single agent or method are avoided. Opioids are usually the mainstay agents and are used in combination with NSAIDs or local anesthetics.

Pre-emptive analgesia is designed to reduce the impact of noxious stimuli on the CNS and involves administration of analgesic agents before the event that will produce the noxious stimuli occurs.

Equianalgesia (A – 10) refers to the dosages and frequencies of various opioid analgesics that provide approximately the same pain relief. An equianalgesic chart (A – 11) lists oral and parenteral doses that are approximately equal to each other; the equianalgesic dose serves as a basis for the selection of the appropriate starting dose when one opioid or route of administration is replaced with another.

Tapering Opioid Doses Before Discontinuation of Therapy

If a patient has received an opioid for more than 3 weeks and is ready to stop taking the medication, his or her dose should be tapered (i.e., slowly decreased) to prevent symptoms of withdrawal. Typically, tapering the dose of the opioid is done by decreasing the dose by 20% every other day.If the patient shows signs of withdrawal (flu-like symptoms, abdominal cramping, diarrhea), the dose should be decreased by a smaller amount over a longer period of time.

Like opioids, benzodiazepine doses should be tapered before they are discontinued; however, the tapering of benzodiazepine doses should be done more slowly—generally, the dose should be decreased by 10% every 3 days.

Side Effects of Pain Treatment

Knowledge of effective pain management includes a thorough understanding of the numerous side effects that could be due to pain medications. The most common side effects (A – 12) associated with opioid therapy are constipation, sedation, pruritus, nausea and vomiting. Nurses must use pharmacologic and nonpharmacologic interventions to provide relief from side effects. It is essential to understand that pain management should continue in the presence of side effects.

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Helpful Web Sites

International Association for the Study of Pain http://www.iasp-pain.org/terms-p.html

The MayDay Pain Project http://www.painandhealth.org/pediatric-links.html

Pediatric Pain, Science Helping Children IWK Health Centre, Psychology Department of Dalhousie University, Halifax, Nova Scotia, Canada http://pediatric-pain.ca/proreshp.html

Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX This Web site contains a comprehensive handbook on cancer pain assessment and management in children. The handbook can be downloaded. http://www.childcancerpain.org/frameset_nogl.cfm?content=handbook.html

Equianalgesic Chart – Duke University Medical Center http://www2.mc.duke.edu/9200bmt/equianalgesia.htm

Critical Facts About Equianalgesia – Massachusetts General Hospital, Boston, MA http://www.massgeneral.org/painrelief/Equianalgesia.pdf

Starting Doses and Conversion Factors for Commonly Prescribed Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX http://www.childcancerpain.org/content.cfm?content=pharm07

Related www.Cure4kids.org Seminars:

Seminar #86 Pain Assessment and Management in the Pediatric Oncology Patient Linda Oakes, RN, MSN, CC http://www.cure4kids.org/seminar/86

Seminar #637 Chronic Pain in Children and Adolescents: Common Problems, Practical Solutions Melissa Wheeler, MD http://www.cure4kids.org/seminar/637

Seminar #638 Pediatric Cancer Pain Management: the St. Jude Children's Research Hospital Approach Doralina Anghelescu, MD http://www.cure4kids.org/seminar/638

Seminar #696 Controversies in Pediatric Pain management: PCCA by Proxy - Is it Safe? Doralina Anghelescu, MD http://www.cure4kids.org/seminar/696

Seminar #742 Multidisciplinary Pain Management in Pediatric Cancer: Interactive Panel Discussion Doralina Anghelescu, MD; Linda Oakes, RN, MSN, CCNS; Mark Popenhagen, PsyD; Raye Pietruszka, MA, CCLS; Deborah Ward, PharmD; and Tori Marchese, PhD, PT http://www.cure4kids.org/seminar/742

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APPENDIX

A – 1 Groups That Have Developed Recommendations, Assessment and Management Guidelines and Treatment Algorithms for Pain

World Health Organization (WHO) http://www.who.int/cancer/palliative/painladder/en/),

National Comprehensive Cancer Network (NCCN) http://www.nccn.org/professionals/physician_gls/PDF/pediatric_pain.pdf

International Association for the Study of Pain (IASP) http://www.tmjpain.org/main_m/w_n_01.htm

American Pain Society (APS) http://www.ampainsoc.org/about/ethics.htm http://ampainsoc.org/advocacy/pediatric.htm

Agency for Health Care Policy and Research/Agency for Healthcare Research and Quality (AHCPR/AHRQ) http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.32374 http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.18803

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A – 2 Recommendations from the American Pain Society and the American Academy of Pediatrics

 Expand knowledge about pediatric pain and principles and techniques of pediatric pain management.  Provide a calm environment in which procedures are performed. Calmness reduces distress-producing stimulation.  Use appropriate tools and techniques for pain assessment.  Anticipate predictable painful experiences, and intervene and monitor accordingly.  Use a multimodal approach (pharmacologic, cognitive, behavioral and physical) to manage pain, and use a multidisciplinary approach when possible.  Involve the patient’s family, and tailor interventions to meet the needs of the individual patient.  Serve as an advocate for the effective use of pain medication for children and adolescents to ensure compassionate and competent management of their pain.

Principles in Managing Pain Related to Procedures (Zelter et al., 1990; http://www.childcancerpain.org/frameset.cfm?content=proced01)

Prepare the patient and parent(s) for possible procedure-related pain by using specific interventions. 1. Provide maximum treatment of pain and anxiety for the initial procedure. This approach will reduce the subsequent development of anticipatory anxiety. 2. Provide adequate knowledge of behavioral and pharmacologic treatment of acute pain and anxiety. 3. Use appropriate monitoring and resuscitative equipment in the procedure room when sedation is used. 4. Ensure that the persons who plan to perform pediatric procedures have adequate mechanical skill. 5. Evaluate the patient continually to assess the efficacy of treatment for pain and anxiety. 6. Create as pleasant an environment as possible in the treatment room.

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A – 3 Treatment Plan—Individualization and Optimization Grossman, SA, Baumohl, J. Cancer Pain. Best Practice of Medicine http://merck.micromedex.com/index.asp?page=bpm_report&article_id=CPM01ON246§ion=report&ss=3

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A – 4 Types of Analgesics and Examples of Each Type

Nonopioids Opioids Adjuvants Acetaminophen Mu Agonist (full agonist, pure agonist, Multiple uses in treating chronic (Tylenol; Tempra, APAP, Panadol) morphine-like) pain Codeine (Tylenol # 3) Antidepressants such as Fentanyl (Duragesic patch) Amitriptyline (Elavil) Hydrocodone (Lortab, Vicodan) Desipramine (Norpramin) Hydromorphone (Dilaudid) Nortriptyline (Aventyl; Levorphanol (Levodromoran) Pamelor) Meperedine (Demerol) Methadone Corticosteroids Morphine Dexamethasone (Decadron) Oxycodone (OxyContin, Percocet) Propoxyphene (Darvon) Psychostimulants Dextroamphetamine (Dexedrine) Methylphenidate (Ritalin) NSAIDs Agonist-Antagonist Multiple uses in treating moderate Aspirin Buprenorhine (Buprenex) to severe acute pain Carprofen (Rimadyl) Butorphanol (Stadol) Anesthetics such as Diflunisal (Dolobid) Dezocine (Dalgan) Lidocaine Etodolac (Lodine) Nalbuphine (Nubain) Ketamine Fenoprofen (Nalfon) Pentazocine (Talwin) Ibuprofen (Motrin, Advil) Ketorolac (Toradol) Ketoprofen (Orudis) Meclofenamate (Meclomen) Mefenamic acid (Ponstel) Nabumetone (Relafen) Naproxen (Naprosyn) Naproxen sodium (Anaprox, Aleve) Piroxicam (Feldene) Salsalate (Disalcid) Continuous Neuropathic Pain Antidepressants Amitriptyline (Elavil) Oral Anesthetics Mexiletine Lancinating Neuropathic Pain Anticonvulsants Gabapentin (Neurontin) Carbamazepine (Tegretol) Phenytoin (Dilantin) Clonazepam (Klonopin) Valproic acid (Depakene) Malignant Bone Pain Corticosteroids Dexamethasone Calcitonin Reprinted with permission from McCaffery, M and Pasero, C. Pain Clinical Manual, p. 109. 1999. CV Mosby.

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A – 5 WHO Analgesic/Pain Ladder

Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX Cancer Pain Management in Children http://www.childcancerpain.org/content.cfm?content=pharm03

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A – 6 Non-Opioid Analgesics NSAIDs (Nonsteroidal Anti-inflammatory Drugs)

Acetaminophen –brand name: Tylenol Ibuprofen- brand name: Motrin

Acetylsalicylic Acid- brand name: Aspirin St. Joseph

Special formulations of children’s ibuprofen have been designed to relieve pain and to relieve fever for a longer period of time. One example is Children’s MOTRIN* (Ibuprofen), which effectively relieves a child’s pain and relieves a child’s fever for as long as 8 hours. These formulations of ibuprofen are usually found next to the adult pain relievers in the pharmacy section.

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A – 7 Papaver somniferum – Source of Opioids

www.nih.gov Meperidine (Demerol) should not be used to manage chronic pain in children because it can cause seizures. In addition, Demerol is typically administered intramuscularly (IM) and because this type of administration (IM injection) is painful, children have been known to “play down” their pain to avoid the injection.

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A – 8 Adjuvant Drugs

Clonidine, brand name: Catapres Capsaicin (over the counter). Brand name: Zostrix, Salonpas Pain relieving patch

Neurontin (gabapentin). Propanolol, brand name: Inderal Brand name : comesin oral solution

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A - 9 Patient-Controlled Analgesia (PCA) Pump

Stanford University School of Medicine, Stanford, CA Stanford Medical Staff Update http://www-med.stanford.edu/shs/update/archives/JULY2004/pca.html Go Back

A - 10 Equianalgesia

Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX Cancer Pain Management in Children http://www.childcancerpain.org/content.cfm?content=pharm18 Go Back Module 9 - Document 7 Page 15 of 18 Management of Pain

A – 11 Equianalgesic Conversion

Drug Onset Peak 1 ½ hours Equianalgesic Doses (minutes) (Hour) IV/IM Oral (mg) (mg) Codeine 10-30 0.5 – 1 3 120 200 Fentanyl 7 -8 ND 1.5 – 6 0.1 NA Hydrocodone ND ND 3.3 – 4.5 ND ND Hydromorphone 15 – 30 0.5 – 1 2 – 3 1.5 7.5 Methadone 30 – 60 0.5 – 1 15 – 30 10 20 Morphine 15 – 60 0.5 – 2 1.5 – 2 10 60 Oxycodone, P.O. 15 - 30 1 ND NA 30 Oxymorphone 5 – 10 0.5 – 1 ND 1 10 From: Pharmacy Department, Texas Children’s Hospital, ND = No Data; NA = Not Applicable

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A – 12 Side Effects of Pharmacologic Pain Interventions and Management

Pharmacologic Agent Side Effects Nursing Intervention Acetaminophen Considerably fewer side effects Teach the patient about multiple Liver toxicity trade names and the use of this Higher doses correlated with renal disease drug as an additive in OTC medications (e.g., cold medications), which may increase the dose taken. NSAIDs Local GI irritation – heartburn, mild gastritis Implement prophylactic therapy Severe effects– GI ulceration, perforation and bleeding using gastroprotective drugs such as antacids, misoprostol, sacralfate and H2 receptor blockers such as Tagamet or Zantac. Hematologic effects – interference with platelet aggregation causing increased bleeding time

Possible renal insufficiency Increase fluid intake

CNS effects – mild dizziness and drowsiness, cognitive Safety measures dysfunction such as decreased attention span, loss of short-term memory

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Opioids GI effects – delayed emptying, slow bowel motility and Prevent by using stimulant decreased peristalsis laxatives. constipation, nausea and vomiting Determine cause of nausea and vomiting, and treat accordingly with 5HT receptor blocker or Reglan.

Decrease dose; treat with an Pruritus antihistamine.

Confusion, hallucinations, paranoia, clouded Evaluate the underlying cause. consciousness, delirium Switch to another opioid.

Sedation Determine whether the cause is the opioid. Reduce dose if possible; lower dose but increase frequency. Add simple stimulants.

Respiratory depression Monitor sedation and respiratory function. Decrease dose, add nonopioids. Use naloxone, if necessary. Antidepressants Sedation and mental clouding Implement safety precautions. Orthostatic hypotension

Dry mouth, blurred vision Provide oral care, ice chips, chewing gums. Corticosteroids Water retention, Monitor I and O, BP. GI – dyspepsia Teach patient and family. Mood disturbances Tapering dose before DC. Withdrawal symptoms Alpha2-adrenergic Sedation, hypotension, dry mouth Monitor BP, and provide ice chips, agonist (clonidine) gum. Implement safety precautions. Abbreviations: BP, blood pressure; DC, discontinuation; GI, gastrointestinal; I, input; NSAIDs, nonsteroidal anti- inflammatory drugs; O, output. Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX Cancer Pain Management in Children Management of the Side Effects of Opioids http://www.childcancerpain.org/content.cfm?content=pharm11

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Acknowledgments

Cure4Kids.org International Outreach Program St. Jude Children's Research Hospital 332 N. Lauderdale St. Memphis, TN 38105-2794

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