Guidelines for Standard of Care of

Acute Painful Episodes in Patients with

Sickle Cell Disease

 

Developed by:

Samir K. Ballas, MD (1)

Timothy M. Carlos, MD (2)

Carlton Dampier, MD (3)

and the Guidelines Committee

Commonwealth of Pennsylvania

Department of Health

 

1. Cardeza Foundation for Hematological Research

Jefferson Medical College, Thomas Jefferson University

Philadelphia, PA

2. Montefiore University Hospital

University of Pittsburgh Medical Center

Pittsburgh, PA

3. St. Christopher's Hospital for Children

Philadelphia, PA

Commonwealth of Pennsylvania Department of Health

Sponsored by Pennsylvania Department of Health, Governor Tom Ridge

Guidelines Committee Members

Samir K. Ballas, M.D., FACP, FASCP

Chair, Professor of Medicine, Director, Sickle Cell Center Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Joann Adair, R.N.

Director, Newborn Screening & Genetic Services ProgramDivision of Maternal and Child Health, Pennsylvania Department of Health Commonwealth of Pennsylvania, Harrisburg, Pennsylvania

Rev. Walter Brandon

Sickle Cell Patient, President, Sickle Cell Disease Association of America Philadelphia Delaware Valley Chapter, Philadelphia, Pennsylvania

Zemoria Brandon

Executive Director, Sickle Cell Disease Association of America, Philadelphia Delaware Valley Chapter, Philadelphia, Pennsylvania

Timothy M. Carlos, M.D.

Assistant Professor of Medicine, School of Medicine, University of Pittsburgh, Montefiore University Hospital Pittsburgh, Pennsylvania

Carlton Dampier, M.D.

Associate Professor of Pediatrics, Director, Marian Anderson Sickle Cell Care And Research Center, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

Roy N. Gay, M.D., P.C.

Medical Director, Misericordia Hospital, Director, Sickle Cell Program, Philadelphia, Pennsylvania

Neddie Hollis, MSW, ACSW

Executive Director, Sickle Cell Society, Inc., Pittsburgh, Pennsylvania

Rubye Jenkins-Husband, M.S.

Care Coordinator, John F. Kennedy Center, United Neighborhood Facilities, Health Care Corporation, Erie, Pennsylvania

Karen Musser, R.N.

Nursing Services Consultant, Division of Maternal & Child Health, Pennsylvania Department of Health Commonwealth of Pennsylvania, Harrisburg, Pennsylvania

Kwaku Ohene-Frempong, M.D.

Associate Professor of Pediatrics, President, Sickle Cell Disease Association of America, Director, Comprehensive Sickle Cell Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Ronald Rubin, M.D.

Professor of Medicine, Director, Sickle Cell Program Temple University Hospital, Philadelphia, Pennsylvania

Levi Walker, M.D., Internal Medicine

Faculty Member, University of Pittsburgh, Pittsburgh, Pennsylvania

Joseph Wanamaker

Sickle Cell Patient, President, Sickle Cell Patients Committee, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Copies are available from:

Samir K. Ballas, M.D., Cardeza Foundation, 1015 Walnut Street,Philadelphia, PA 19107


Guidelines for Standard of Care of Acute Painful Episodes in Patients with Sickle Cell Disease

Outline

I. Preamble

II. Introduction

Patient's Bill of Rights

Patient's Responsibilities

III. Acute Sickle Cell Painful Episodes

Definition

Description

Types

IV. Pain Assessment

Adults, Children

V. Pharmacologic Management of Pain

A. Management of Pain at Home

B. Management of Pain in the Emergency Room

C. Management of Pain in the Hospital

1. Fixed Schedule of Parental Opioids with Rescue Doses

2. Patient-Controlled Analgesia (PCA)

D. Side Effects of Opioid Analgesics

VI. Non-Pharmacologic Management of Pain

VII. Management of Pain in the Frequent Utilizer of Care Facilities

(Difficult or "Problem" Patients)


I. Preamble

Acute recurrent painful episodes which require treatment with parenteral narcotic analgesics in the Emergency Room and/or during hospitalization is the hallmark of sickle cell disease. Treatment of acute painful episodes is the primary reason for hospital admission in about 90% of adult patients with sickle cell disease.

Medical staff in US hospitals frequently fail to provide adequate relief when dealing with a patient's complaint of pain in general and sickle cell pain in particular. In recent years, standards for the management of acute pain (1) and pain related to terminal cancer (1, 2) have been published. These manuals are good sources of reference for practitioners treating these conditions. They also provide information regarding the appropriate use and monitoring of non-opioid analgesics. These manuals, however, do not consider the management of a chronic pain syndrome, such as sickle cell disease. In contrast to conditions producing acute pain or to a disease such as cancer that generates chronic pain of short duration, the medical management of pain in patients with sickle cell disease poses several unique problems. This singularity exists because of several issues (Table I) the most important of which involve tolerance or substantially increased opioid utilization compared to other patients and the lack of continuity of care. The mechanisms responsible for increased consumption of opioid analgesics in patients with sickle cell painful episodes are not well characterized.

The Sickle Cell Program of the Commonwealth of Pennsylvania has been in existence since 1977 and supports fourteen centers throughout the State. Services provided by the Centers include a comprehensive initial evaluation, periodic follow up evaluations, ongoing medical care including preventive therapy (i.e., penicillin prophylaxis), and special services as needed, including developmental and psychological tests, psychosocial services, and rehabilitative services. Parents of newborns identified through newborn screening, with hemoglobinopathy traits, receive information, counseling and family testing (as requested). Its current budget is $1,577,000 targeted to the primary care of patients with sickle cell disease. To date over 3,000 patients with sickle cell disease have been enrolled in this Program.

Currently, there are about 2,000 patients actively enrolled in the State's Program. The Department of Health of the Commonwealth of Pennsylvania, in response to concerns expressed by patients, their relatives, advocates, community leaders and sickle cell providers about the quality of pain management both in the emergency room and during hospitalization, made a decision to develop guidelines for Standard of Care to establish uniformity of care across the Commonwealth. A request was made by the Department of Health that the directors of the sickle cell centers supported by the Commonwealth of Pennsylvania form a committee to draft Standards of care of acute painful episodes of patients with sickle cell disease based on what is reported in the literature and on their own experience. This communication is the summary of the Committee's recommendations for physicians caring for patients with sickle cell disease. It is hoped that these recommendations will be of value in the total care of patients with sickle cell disease at home, in the office, in the emergency room, and in the hospital.

 

Table I: Obstacles to effective management of Sickle Cell Disease

1. Sickle cell disease is inherited, chronic, and incurable.*

2. Differences in the sociocultural background between patients and health care providers.

3. Heavy use of opioid analgesics by some patients.

4. Failure to distinguish between addiction, dependence, and tolerance by health care providers.

5. Overemphasis by some providers on the addictive effects of opioid analgesics.

6. Lack of continuity of care in some institutions.

7. Lack of lucrative insurance coverage in the majority of patients.

8. A prevalent negative attitude among providers towards patients with sickle cell disease.

* Cure has recently been reported after successful bone marrow transplantation in selected patients.


II. Introduction

A. Patient's Bill of Rights

Patients with sickle cell disease, like any other patient, have rights. Needless to say, all hospitals should endorse a patient's Bill of Rights. This emphasizes that compliance with patient's rights can contribute to effective patient care. Because of their often poor psychosocial background, patients with sickle cell disease may not be aware of their rights. It is expected that care providers and hospitals deliver pain management with an overriding concern for the patients, and, most importantly, the recognition of their dignity as human beings. The contents of a modification of the American Hospital Association's Bill of Rights (3) should be conveyed to patients with sickle cell disease as follows:

1. Patients have the right to considerate and respectful care with recognition of their personal dignity.

2. Patients have the rights to have their property treated with respect.

3. Patients have the right to confidentiality of their records in compliance with legal requirements.

4. Patients have the right to be fully informed in advance of any change in the care or service provided to them and that may affect their well being.

5. Patients have the right to participate in planning care and services or changes in care and services unless they are judged incompetent.

6. Patients have the right to obtain from their certified provider, complete current information concerning their diagnosis, treatment, and prognosis in terms the patients can reasonably be expected to understand. When it is not advisable to give such information to the patient, the information should be available to an appropriate person on their behalf.

7. Patients have the right to receive from their certified provider, information to give informed consent prior to the start of any procedure and/or treatment. This shall include such information as the medically significant risks involved with any procedure and probable duration of incapacitation. Where medically appropriate, alternatives for care or treatment should be explained to the patient.

8. Patients have the right to refuse any and all treatment, to the extent permitted by law, and to be informed of any of the medical consequence of their action.

9. Patients have the right to every consideration of privacy concerning their own medical care program, limited only by state statutes, rules, regulations, imminent danger to the individual or others.

10. Patients have the right to reasonable continuity of care.

11. Patients have the right to be informed of anticipated termination of service by their provider or of plans to transfer their services to another provider.

12. Patients have the right to be advised if the clinician, hospital, clinic, etc. proposes to engage in or perform human experimentation affecting their care or treatment. Patients have the right to refuse to participate in such research projects.

13. Patients have the right to voice grievances about care and services furnished by their provider (or services not furnished) without discrimination or reprisal for their doing so. A grievance procedure should be provided to each patient on admission.

B. Patient's Responsibilities

The flip side of rights is responsibilities. These are as follows:

1. Providing accurate and complete information about their disease, hospitalization, emergency room visits, medications, and other matters relevant to their heath.

2. Treating their providers and ancillary personnel with respect.

3. Complying with instructions related to services and products provided.

4. Cooperating with all personnel (in the clinic, office, emergency room, hospital) and asking questions if they do not understand the information or instructions given to them.

5. Participating in the planning of their care and services as outpatients.

6. Informing the clinic or office when they will not be able to keep an appointment.

7. Providing information and making arrangement (example, obtain referrals) for payment for the services rendered by their care provider.

8. Understanding the management of pain and the need of judicious use of opioid analgesics.

9. Understanding the importance of establishing a trusting environment between themselves and their health care providers.


III. Acute Sickle Cell Painful Episodes

The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. This definition implies at least two important aspects of pain as follows:

1) pain may or may not be associated with objective findings secondary to tissue damage; and 2) it is misleading to speak of pain causing emotions or emotions producing pain, since pain is, in part, emotion. Emotions constitute an essential component of pain. This definition applies extremely well to patients with sickle cell disease and acute painful episodes who present themselves to the emergency room with no evidence of objective signs or major change in their base line data and vital signs (4). Thus, a painful crisis can occur in the absence of all objective signs.

The acute painful sickle cell episode (painful crisis) is the hallmark of sickle cell disease and the most common complaint among patients with this disease. The frequency and severity of these painful episodes vary considerably among patients and in the same patient from time to time. Infection, physical stress, and emotional upheaval may precede a painful crisis. In the majority of patients, however, there is no obvious precipitating factor. Objective signs of tissue damage may be absent especially at the initial phase of the crisis (4, 5). Pain usually involves the low back, legs, knees, arms, chest, and abdomen in decreasing order of frequency. Pain may be throbbing, sharp, dull, or stabbing in nature. Patients with sickle cell disease are also prone to develop other types of pain (both acute and chronic) as listed in Table II.

 

Table II: Major Pain Syndromes in patients with Sickle Cell Disease

Acute Pain Syndromes

Painful episodes

Acute Chest Syndrome

Right Upper Quadrant Syndrome

Hand-Foot Syndrome

Splenic Sequestration

Priapism

Calculus Cholecystitis

Chronic Pain Syndromes

Aseptic (Avascular) Necrosis

Vertebral Body Collapse

Arthropathy

Leg Ulcers

Arthritis


IV. Pain Assessment

A. Pain Assessment in Adults

Reasons for the failure to relieve a patient's pain include the lack of proper assessment of the patient's perception of pain and the failure to monitor results of therapy (1). A comprehensive protocol for assessing pain in adults with sickle cell disease should include the following (6):

1. An Objective Tool for Self-Assessment of Pain and Activity

A verbal pain scale (0 [no pain] - 10 [worst pain imaginable]) should be employed during periods of acute pain, a time when patients may be unable or unwilling to give a written response. Verbal responses are most useful in the emergency department or during the initial day of hospitalization and aid in determining analgesic efficacy during titrated loading doses of medication. A written assessment of pain, e.g., a Visual Analogue Scale (VAS), has been utilized in several studies examining the relief of pain in adult patients with sickle cell disease (7, 8). Of interest, these reports confirm that patients continue to have moderate pain at the time of discharge and suggest that they continue to cope with pain as outpatients. Thirdly, a daily diary noting activity, medication use, and presence or absence of pain has also been shown to provide information regarding the ability of patients to cope with pain as outpatients (9).

2. Other Single Dimension Self-Report Measures

These include pain relief scale, mood scale, and sedation scale. For the pain relief scale patients are asked to indicate the amount of relief (from 0% to 100%) they have from their pain at the time of assessment compared to the previous day or to their first day of hospitalization. For the mood scale, the patient is asked to circle a number from 0 (worst mood) to 10 (best mood) which indicates his/her mood at the time of assessment. Sedation is also graded by the examiner from 0 (fully awake) to 10 (deep sleep).

Patients are also asked to give a verbal description of their pain and to indicate whether the pain is similar to their usual crisis pain or not. Pain that is not typical of crisis is a signal to conduct a thorough search for other causes of pain.

3. Location of Pain

The spatial distribution of pain is documented by asking the patients to mark the area of pain on a scaled drawing of the body. Fig. 1 represents a scheme where single dimension self-report measures as well as the location of pain are documented at least once every day.

4. An objective Assessment of Coping Strategies

Coping strategies should be assessed through structured interview techniques or standard questionnaire [e.g., Coping Strategies Inventory (10)]. These are best performed as outpatient when patients are not experiencing a concurrent crisis.

5. An Assessment of Social and Environmental Factors that May Influence the Pain Experience

Sickle cell disease has an impact on the entire family. A multidisciplinary approach to pain management should assess the role of the spouse and other family members in the patient's response to treatment (6). Included in this assessment is an evaluation of the patient's and family's understanding of the pain and its management. Marital satisfaction, satisfaction with social support elements, performance at school or work, and participation in activities of daily living and social interactions should be assessed. As with assessing coping strategies, examinations of social and environmental factors should be made during pain-free interludes.

6. Indices of Health Care Utilization

Patients with a high-risk behavior for frequent use of medical services should be identified. Patterns of high-risk behavior include increasing medication usage, failure in school or employment, increasing hospitalizations, and adversarial relationships with health care providers (6). The frequency of painful episodes, number of emergency room visits, frequency and duration of hospitalizations, and need for analgesic medication should also be assessed.

B. Pain Assessment in Children (8, 11-14)

There is no question that sickle cell pain occurs in children, and that this pain represents an aversive stimulus which likely has a detrimental effect. Such pain deserves pain relief as it does in adult patients, yet the assessment of sickle cell pain in children presents some unique challenges. Such pain occurs across the pediatric age group from infants to adolescents, and can occur in many different parts of the body and in many different clinical contexts. The concomitant behaviors that these patients may display in response to this pain is likely to be age specific, as is their ability to provide meaningful self-reports of their pain experience. For the purpose of this discussion, pediatric patients will be broken into four age groups: adolescents (13-20 years), and school-age children (6-12 years), preschool children (3-5 years), and infants (0-2 years).

1. Adolescents

These patients have many of the features of young adult patients. Several studies have shown the validity and reliability of a variety of self-reports of pain intensity. These include typical visual analogue scales (VAS) and verbal categorical scales of 0-10 or 0-100. They also have been shown to appropriately use body diagrams or outlines to locate their pain. The ease of use of adjectives to describe their painful experience will likely depend on their educational level. In general, most such scales for adolescents have selected a subset of words from adult questionnaires or have asked them to volunteer their own descriptors.

There is little or no data on the type of pain behaviors typically displayed by adolescents during their pain episodes. In general, they report engaging in less motor activity (e.g. sports, and going to school) when in pain. The degree to which severe pain limits their ability to engage in daily living activities, or causes them to display typical pain behavior (grimacing, vocalization, guarding, etc.) likely varies with personality and coping styles as it does in adult patients. Some adolescent patients may be particularly anxious about their pain experience, as their sickle cell disease may have been relatively less symptomatic prior to that event. Other adolescents may engage in controlling types of behavior as this is a particularly important issue at this stage of their lives. We have also seen some adolescents who become severely depressed as they begin to realize how much their pain and their underlying disease may interfere with the lifestyle in which they may wish to engage. Thus an interpretation of an adolescent's self-report of pain and their actual pain related behavior will be assisted by understanding them as individuals, and understanding what the pain experience means in the context of their lives. Better understanding of these issues could be obtained with psychological testing using standardized methods.

2. School-Age Children

Pain assessment begins to become complicated in this age group. The use of VAS and categorical scales with many intervals requires a concept of relative line length and other related elementary arithmetic concepts. Depending on the child's educational level and maturity, these scales may not be useful for the younger children in this age group. However, with appropriate explanations and practice, the older children in this age group can use them in a valid and reliable fashion. The use of words to describe pain characteristics may again be problematic in the younger children in this age group because of limited ability to read, and a limited expressive vocabulary. To effectively communicate with these younger children, it is particularly important to understand what words or expressions are used in the home to express levels of pain or discomfort.

Interpreting pain related behavior in this age group is similarly difficult. Some of the older children in this age group may have similar issues to those of the adolescent patients, while for the younger children fear and anxiety about the hospital experience itself may be a dominate feature. They may not want to report pain because they expect such a report may lead to further venipuncture or intramuscular injections, whose associated anxiety may make these procedures worse than their sickle cell pain.

 

Fig. 1: Pain Assessment Tool (adapted from reference #1, 2)

Date:

Time:

1. Please Circle The Number That Best Describes Your Pain.

0 1 2 3 4 5 6 7 8 9 10
No Pain Worst Possible Pain

 

2. Please Circle The Number That Best Describes Your Belief Of Pain.

0 1 2 3 4 5 6 7 8 9 10
No Pain Complete Relief

3. Shade the figure where you feel pain.

4. Mark an X where you hurt most.

3. Pre-School Children

There have been no published studies of pain assessment of sickle cell pain in this age group. We must currently assume that pain assessment tools developed to assess the intensity of post-operative or arthritis pain will be similarly valid for sickle cell pain. These tools consist of small interval categorical scales (3-4 intervals) often using visual markers. One such scale uses poker chips to represent amounts of pain or "hurt", while another popular tool asks the child to use several different colored crayon to shade on a body outline where their pain is located and how much it hurts. Some of these tools may also be useful for the youngest school-age children. Some of the youngest children in this age group may do better using a categorical scale based on a series of pictures on the faces of ethnically appropriate infants with pain, the "oucher" scale. A methodologic difficulty of such scales is the inability to separate intensity from effective experience, but that may not be a clinically useful distinction in this age group. All of these scales require considerable patience and understanding and a relatively cooperative subject. Assessment of pain related behavior is difficult. Clinically one often relies on the parent's judgement of how their child's behavior is different from their usual activity or temperament.

4. Infants

Assessment tools for this age group are not available for any type of non-procedure related pain. A number of observational scales of behavior associated with heal lancing, immunizations, etc. have been documented but their application to other pain states is doubtful. Similarly, acute changes in some physiologic variables such as heart rate, blood pressure, etc. may have some validity in these situations as indirect measures of the intensity of the infants pain experience. Since the sickle cell pain of this age group typically involves their hands and/or feet, we have often used their motor ability in these areas (walking, weight bearing, gripping a bottle) as indirect measures of pain. Similarly, global changes in infant behavior as observed by a parent may have some validity.

V. Pharmacologic Management of Pain

A. Management of Pain at Home

Treatment of acute painful episodes is empiric and depends on the severity of pain. Patients often feel that a painful crisis is impending and early treatment with analgesics may abort or ameliorate an evolving painful episode. Home treatment of pain should follow the Three Step Analgesic Ladder (Table III) proposed by the World Health Organization (15). This approach involves the use of escalating potency of analgesics. These medications are given alone or in combination initially on an "as needed" followed by an "around the clock" administration of analgesics for moderate-severe pain. The use of this model has been shown to control pain in 90% of cancer patients (2).

 

Table III: Sickle Cell Painful Episodes

Home Management

I. Pharmacologic Management

The WHO Three-Step Analgesic Ladder

A. Step I - Mild Pain

Non-opioid " Adjuvant

B. Step II - Moderate Pain

Weak Opioid " Non-Opioid " Adjuvant

C. Step III - Severe Pain

Strong Opioid " Non-Opioid " Adjuvant

II. Non-Pharmacologic Management

Heating Pad

Relaxation

Diversion

Self-Hypnosis

Motivation

Step 1: For mild pain, non-opioid analgesics are used as needed (Table IV) with or without adjuvants (Table V).

 

Table IV: Selected Non-Opioid Analgesics (Adapted from Reference #1, 2)

Drug

Average Analgesic Dose (mg)

Comments/Side Effects

Acetainophen

Adults: 500-1000 q4-6h

Children: 10-15/Kg q4-6h

Risk of liver damage.

Salicylates

1. Aspirin

2. Diflunisal

3. Choline Magnesium

Trisalicylate

Adults: 650-1000 q4-6h

Children: 10-15/Kg q4h

Adults: Initial 1000 q8-12h

Then 500 q8-12h

Children: None Available

Adults: 1000-1500 q12h

Risk of gastritis, bleeding; may cause liver damage in patients with pre-existing liver disease; monitor renal function. Contraindicated in viral illnesses in children.

Same as ibuprofen.

Like aspirin except platelet effect.

Children: 25/Kg bid

Also available in liquid form.

Propionic Acid Derivatives

1. Ibuprofen

2. Naproxen

3. Naproxen Sodium

4. Fenoprofen

5. Ketoprofen

Adults: 200-400 q4-6h

Children: 10/Kg q6-86

Adults: Initial 500 q6-8h

Then 250 q6-8h

Children: None Available

Adults: Initial 550 q6-8h

Then 275 q6-8h

Children: None Available

Adults: 200 q4-6h

Children: None Available

Adults: 25-50 q6-8h

Children: None Available

Same as aspirin; reversible platelet effect. Available in both tablet and liquid form. Advil brand may be preferred as the tablet is sugar coated.

Like ibuprofen. Also available in liquid form.

Like ibuprofen

Like ibuprofen

Like ibuprofen

Acetic Acid Derivatives

1. Indomethacin

2. Ketorolac

Adults: 25 q8-12h

Children: None Available

Adults: Initial 30-60 IM q6h

Then 15-30 IM q6h

Children: None Available

High incidence of gastritis

Like ibuprofen

Because pain associated with sickle cell disease is episodic, patients are accustomed to taking analgesics on a prn (as needed) basis. The advantages of employing non-opioids for mild pain include the following (2): 1) they are useful in the treatment of mild to moderate pain; 2) these medications are widely available; some of the medications do not require a prescription so that access to medical staff is not required; 3) additive analgesia can be obtained when combined with opioids and other modalities; 4) these drugs can be administered by patient or family making home management of pain feasible; 5) some of these medications are inexpensive; and 6) they do not produce tolerance or physical/psychological dependence.

 

Table V: Commonly Used Adjuvants in Pain Management

Antihistamines

Hydroxyzine (Vistaril, Atarax)

Diphenhydramine (Benadryl)

Tricyclic antidepressants

Amitriptyline (Elavil, Endap)

Doxepin (Sinequan)

Imipramine (Tofranil)

Nortriptyline (Pamelor)

Desipramin (Norpramin)

Benzodiazephines

Alprazolam (Xanax)

Chlordiazepoxide (Librium)

Clorazepate dipotassium (Tranxene)

Diazepam (Valium)

Flurazepam (Dalman)

Lorazepam (Ativan)

Oxazepam (Serax)

Triazolam (Halcion)

Anticonvulsants

Phenytoin (Dilantin)

Carbamazepine (Tegretol)

Clonazepam (Klonopin)

Laxatives

Stool Softeners

Stimulants

Antiemetics

Prochlorperazine (Compazine)

Metochlorpramide (Raglan)

However, there are disadvantages to these medications as well (2). There is a "ceiling effect" to analgesia produced by these drugs; increasing dosage generates adverse side effects without gaining further analgesia. These side effects include hepatotoxicity (aspirin, non-steroidal antinflammary drugs [NSAIDs], and acetaminophen) and renal toxicity (aspirin and NSAIDs). These toxicities should not be minimized since 10-15% of patients with sickle cell disease have hepatic or renal damage due to their hemoglobinopathy (16, 17). Patients with liver disease can develop severe hepatotoxicity even when acetaminophen is taken in usual therapeutic doses. Risk factors for NSAID-induced acute renal failure include congestive heart failure, chronic renal failure, and intravascular volume depletion (18). Patients with sickle cell disease continually are at risk for developing dehydration due to an inability to concentrate their urine (hyposthenuria). Thus, hepatic and renal functions should be monitored when using these analgesics for prolonged periods. Finally, one NSAID (ketorolac) is available for parental administration. Parenteral ketorolac, however, has been reported to be as effective as 6-12 mg of IM morphine sulfate (1). In addition, many of the newer NSAIDs are expensive.

Patients may vary in their relative response to NSAIDs. Therefore, if a patient with pain does not respond to a particular drug, an alternative NSAID should be considered.

Step 2: For moderate pain, fixed doses (i.e., around the clock) of a non-opioid are used and a weak opioid (codeine or oxycodone) (Table VI) is added, first as needed and then as a fixed dose with or without an adjuvant.

While in general there is no ceiling effect with opioids, weak opioids tend to have significant dose-limiting side effects (e.g., constipation, nausea, vomiting) when they are used in higher doses to manage moderate to.

Patients with sickle cell disease commonly use analgesic combinations containing acetaminophen and either codeine or oxycodone to relieve pain. While the latter opioids are considered weak agents, the amount of acetaminophen in these formulations should not be neglected. Ingestion of no more than 12 tablets of acetaminophen-oxycodone daily is the suggested safe limit in normal individuals (1). Since patients with sickle cell disease may have concurrent liver disease, the total daily use of these analgesics should be monitored.

Table VI: Commonly Used Weak Opioid Analgesics (Adapted from Reference #1, 2)

Drug

Average Analgesic Dose (mg)

Comments/Side Effects

1. Codeine

Adults: 30-60 q3-4h

Children: 1/Kg q3-4h

Impaired ventilation.

Histamine release may trigger bronchospasm. Increased intracranial pressure from CO2 retention. Liver failure. Oral route is preferred; available in both liquid and tablet form either alone or in combination with acetaminophen.

2. Oxycodone

Adults: 5-10 q2-3h

Children: 0.2/Kg q3-4h

Same as codeine.

Use in combination with acetaminophen limits safe daily dose to 12 tablets (about 4g acetaminophen). Oral route is the only available preparation.

 

Table VII: Commonly Used Opioids For Severe Pain (Adapted from Reference #1, 2)

Drug

Oral Dose

Parenteral (mg)

Comments/Side Effects Dose (mg)

1. Morphine

Adult: 15-30 12-3h

Children: 0.3/Kg q3-4h

5-10 q2-3h

0.1/Kg q3-4h

Caution in patients with impaired ventilation, asthma, increased intracranial pressure, liver failure.

2. Hydromorphone

Adults: 4-8 q2-3h

Children: 0.06/Kg q3-4h

1.5-4 q2-3h

0.015/Kg q3-4h

Like morphine; slightly shorter duration.

3. Methadone

Adults: 5-10 q6h

Children: 0.2/Kg q6-8h

2.5-5 q6h

0.1/Kg q6-8h

Like morphine; good oral potency; long plasma half-life (24-36h); may accumulate with repetitive dosing causing excessive sedation (days 2-5). May switch to bid or q day dosing after loading dose.

4. Levorphanol

Adults: 2-4 q6-8h

Children: 0.04/Kg q6-8h

q6-8h

2-4 q4-6h

0.02/Kg q6-8h

Long plasma half-life (12-16h); like methadone may accumulate days 2-3. Expensive.

5. Meperidine

Adults: 100-200 q2-3h

Children: 1-1.5/Kg q4-6h

50-100 q2-3h

Short acting; metabolite (normeperidine) accumulates and has longer half-life (18h); normeperidine causes CNS excitation (seizures, tremor); avoid in patients with impaired renal function or who are receiving monoamine oxidase (MAO) inhibitors; avoid chronic use. Not recommended in most, but not all, patients.

6. Fentanyl

N/A

0.1*

Transdermal delivery system; 25 microgram patch equivalent to 30 mg sustained-release morphine q8h; delay of 12h in onset and offset due to skin reservoir of drug; fever increases dose rate. Not recommended in acute painful episodes.

*Not Recommended for routine use.

Step 3: For severe pain a strong opioid (morphine, hydromorphone, methadone, meperidine) (Table VII) is used in conjunction with a non-opioid " an adjuvant. It should be emphasized that patients may initiate their pain therapy at any rung of the ladder, depending on pain severity and post experience, and not necessarily in sequential order. Meperidine is commonly used in the treatment of pain due to sickle cell disease especially in adults.

However, there are strong justifications for not using this analgesic in patients with sickle cell disease. While the half-life of meperidine is only 3 hours, the half-life of normeperidine, a toxic metabolite, is 18 hours. Thus, the metabolite will invariably accumulate even in patients with normal renal function. Normeperidine is a central nervous system excitotoxin that produces anxiety, tremors, myoclonus, and generalized seizures when it accumulates with repetitive dosing. The incidence of seizures in patients with sickle cell disease related to use of meperidine varies between 1 and 12% (19-21). Oral meperidine has only 25% of the analgesic effectiveness but produces just as much normeperidine.

Factors associated with the occurrences of seizures in patients treated with meperidine are: 1) doses greater than 100 mg q 2h; 2) alkaline urine (decreased excretion of normeperidine), 3) co-administration of phenobarbital and other enzyme-inducing drugs (increased production of normeperidine due to increased metabolism), 4) co-administration of phenothiazines (lowers seizure threshold), and 5) a history of seizures. Patients with impaired renal function are particularly at risk. Since acute pain due to sickle cell disease typically lasts 5-7 days (6), if meperidine is used it should be limited to no more than 48 hours and daily doses should be less than 1200 mg/day unless the history indicates that the patient in question usually tolerates larger doses for a longer period of time.

It should be emphasized that seizures caused by high doses of morphine and methadone have been reported (22). The incidence of seizures caused by these drugs in adult patients with sickle cell disease is not known perhaps because they have not been used on a large scale for a long time as is the case with meperidine.

The role of partial agonists (Buprenorphine) and mixed agonists-autogonists (Pentazocine, Nalburphine, Butorphanol) in the treatment of acute sickle cell painful episodes is not known at the present time. Thus, it may be advisable not to use them especially in adults who are tolerant to opioid agonists. Partial agonists and mixed agonists-autogonists have a ceiling effect and have serious undersirable side effects such as delusion, dysphoria, hallucinations, panic, and precipitation of acute withdrawal in patients using opioid agonists.

B. Management of Pain in the Emergency Room

Acute pain in sickle cell patients often is initially treated in a standard fashion by medical staff: a dose of opioid that would seem to be appropriate is chosen and is delivered as needed to relieve pain. The dose may be too much for the opioid-naive patient leading to excessive sedation and, at worst, respiratory depression. Conversely, the chosen dose may be insufficient for the opioid-tolerant sickle cell patient. In this situation the patient continues to suffer in pain. The medical staff then assumes that, since an apparently appropriate dose did not resolve the patient's complaints, the patient is manifesting drug-seeking behavior. By individualizing the quantity of loading doses and by employing objective scales to confirm relief of pain, acute pain due to vaso-occlusive crises can be controlled expeditiously.

Evaluation and assessment in the emergency ward should include a thorough history and physical exam. Hemotologic determinations including a reticulocyte count should be performed and compared to steady-state values. Signs and symptoms of infection should be sought for. Specific organ systems, including the central nervous system, cardiopulmonary, hepatobiliary, genitourinary, and musculoskeletal systems, should be systematically evaluated for involvement. Patients are the best authority on their pain. If their pain is not typical of their usual crises, other causes of pain should be examined aggressively. The presence of other causes of pain or organ system involvement should be managed according to the specific findings.

When the initial evaluation suggests an uncomplicated painful episode, further assessment of the pain should ensue as described above. Pain of mild severity may be treated with oral non-opioid analgesics or weak opioids according to the three-step ladder described above. Most adults, however, come to the emergency room only after these measures have failed at home, so their treatment entails the parenteral use of strong opioid analgesics directed at relieving pain promptly. The specific opioid analgesic to be used varies from patient to patient, time to time, and center to center.

Other measures such as hydration (oral or intravenous), heating pad, and nonpharmacologic methods also are used. There is no evidence that oxygen inhalation reduces the intensity or duration of pain, and its use should be reserved for those patients who have pulmonary complications resulting in hypoxemia.

Adjuvants (Table V) are used in conjunction with the opioid analgesics to enhance the analgesic effect and prevent or ameliorate pruritis. Opioid analgesics (Morphine, Hydromorphone, or Meperidine) should be given regularly, usually every 2 hours IM or IV. The intravenous route is the preferred method of opioid delivery particularly in children. The IM route may be necessary in these patients with poor vascular access or those who insist on IM injections because of past habit. The best guide for the initial amount to be used is the dose the patient required in the past.

Patients should be reassessed periodically after the initial dose of the opioid analgesic. With parenteral administration, reassessment should take place 30 minutes after the initial dose. If there has been absolutely no pain relief or sedation, 50 percent of the initial dose can be repeated 30 min after the previous dose. If a patient is mildly sedated and still has significant pain, then 25 percent of the dose should be repeated 30 minutes after the previous dose. Close monitoring of vital signs and the availability of a physician experienced in the use of opioids in this manner are essential for the success of this approach. The respiratory rate is most important in monitoring potential serious side effects. A rate of <10/min is a sign of respiratory depression and an indication to discontinue opioids temporarily and reduce the subsequent dose.

The disposition of the patient in the emergency ward depends on the results of the management described above, evaluation, assessment, and specific treatment. The opinion of the patient regarding the need for hospitalization versus attempting to resolve the crisis in the emergency ward may provide helpful guidance for prompt disposition. Suspected infection and organ involvement may necessitate prompt hospital admission. If the pain is relieved, the patient may be discharged with a prescription for a limited amount of opioid analgesics to treat resolving pain. Failure to achieve adequate pain relief after treatment for 6 to 8 hours in the emergency department is an indication for hospital admission. Table VIII outlines one scheme for treatment in the emergency room.

C. Management of Pain in the Hospital

Failure to break the painful crisis in the emergency room is an indication for hospital admission. Management of pain in the hospitalized patient is essentially a continuation of the process of evaluation, assessment, and titration of the dose of opioids to achieve adequate pain relief. This can be done either by 1) parenteral administration of opioid analgesics on a fixed schedule with rescue doses, or 2) patient controlled analgesia as follows:

1. Fixed Schedule of Parenternal Opioids With Rescue Doses (Table IX). Pain therapy during the first 2-3 days of hospitalization should be aggressive with ongoing assessment of pain intensity and titration of the dose of opioid analgesics to achieve pain relief. Analgesia should be given parenterally on a fixed schedule (usually every 2 hours) and not on an "as needed" basis. The pain should be assessed every 30 to 60 minutes and the dose of the opioid titrated with rescue injection equal to 25-50% of the initial dose. If three or more rescue doses are needed within 24 hours or less to achieve adequate pain relief, the initial dose should be increased by 25-50% and the process repeated until adequate pain relief is achieved. Sedation and vital signs should be monitored as described above.

 

Table VIII. Treatment of Acute Sickle Cell Pain in the Emergency Room

1. Believe the patient.

2. Conduct thorough clinical assessment periodically, including documentation of pain severity, and pain relief.

3. Select the appropriate opioid analgesic and its dose based on previous history.

4. Administer opioid analgesics parenterally on a regular basis (maintenance dose).

5. Monitor sedation and vital signs with special attention to the respiratory rate (RR).

6. Titrate the maintenance dose opioid analgesic (taper or escalate).

7. Give rescue doses (1/4-1/2 maintenance dose) for breakthrough pain every 30 minutes.

8. Decrease or skip maintenances dose if RR <10/min or if severely sedated.

9. Give non-opioid analgesics and adjuvant analgesics in combination with opioid analgesics.

10. If the acute painful episode is broken and pain is relieved the patient may be discharged from the emergency room.

11. Give limited amount of analgesic medication or a prescription for pain medication to treat resolving pain.

12. Failure to achieve adequate pain relief after aggressive therapy in the 6 to 8 hours is an indication for hospital admission.

 

Table IX: Treatment of Acute Sickle Cell Pain in the Hospital

Method A: Fixed Schedule of Parenteral Analgesia with Rescue Doses

1. Believe the patient.

2. Conduct thorough clinical assessment periodically, including documentation of pain severity and pain relief.

3. Select the appropriate opioid analgesic, its dose, and frequency of administration based on previous experience.

4. Administer opioid analgesics parenterally (preferably IV) on a regular basis usually every 2 hours in adults (maintenance dose).

5. Give non-opioid analgesics and adjuvants in combination with opioid analgesics. NSAIDs are contraindicated in the presence of impaired renal and/or hepatic function and history of gastropathy.

6. Monitor sedation and vital signs with special attention to the respiratory rate.

7. Assess pain severity every 30 minutes.

8. Give rescue doses (25-50% of maintenance dose) for breakthrough pain every 30 minutes if adequate pain relief is not achieved.

9. If three or more rescue doses are needed in 24 hours or less increase the maintenance dose by 25-50% and follow the same procedure of assessment and dose adjustment.

10. Decrease or skip maintenance dose in the presence of severe sedation or if RR is <10/min.

11. After 2-3 days of therapy decrease the maintenance dose by 25% every 24 hours and replace with an oral opioid in divided doses on a regular basis.

12. After 24-48 hours the oral opioid may be given as needed. If pain relapses escalate the dose into its previous level of administration.

13. Patients may be discharged if they are pain free with no co-morbid condition or if pain is adequately controlled with oral analgesics.

14. Design a discharge plan with follow up as an outpatient.

After 2-3 days of this aggressive parenteral therapy the loading dose may be decreased by 25% every 24 hours. Replace the decreased parenteral amount by an oral equianalgesic dose on a fixed schedule. It is advisable to use the same opioid parenterally and orally whenever possible. Table X summarizes the equianalgesic oral and parenteral doses of the major opioid analgesics. If pain assessment shows continued improvement, proceed with decreasing the parenteral opioid analgesic by 25% everyday and replace with an equianalgesic oral dose. After 24-48 hours the oral opioid may be given as needed. If pain relapses escalate the dose to the previous level of administration.

Patients may be ready for discharge if they are pain free or if their pain is adequately controlled with oral analgesics. Give enough medication upon discharge to treat resolving pain and to last until their next office appointment with their primary care physician.

Table IX outlines the major steps of this method of therapy of hospitalized patients.

2. Patient Controlled Analgesia (PCA) (Table XI)

Patient controlled analgesia (PCA) may be an ideal method of treating acute pain in the majority of sickle cell patients (6, 18). After an effective loading dose of an opioid analgesic, the patient can elicit an analgesic bolus by activating a demand switch causing a preset dose of opioid to be delivered if a predetermined time (lockout interval) has elapsed since the previous dose. Thus, PCA allows patients considerable control over the experience of pain and produces an overall improvement in analgesia without significant increase in sedation.

The standard PCA infusion pumps allow limitation of cumulative doses over 1-4 hours. Patient administrated doses, lockout intervals, and 4 hour limits must be based on the required loading dose and presence of opioid tolerance. Experience in post-operative patients have demonstrated that patients will titrate themselves to minimally effective analgesic concentrations and will not overdose themselves to produce significant adverse effects such as sedation or respiratory depression.

An example of one method employing PCA in the management of acute pain in adult sickle cell patients involves the following (Table XI [23]). An initial verbal pain score is recorded and the patient is then loaded with small boluses of either morphine (2.5-10 mg), hydromorphone (0.5-2.0 mg) or merperidine (2.5-10 mg) every ten minutes intravenously. Following each bolus, the verbal pain score is repeated. Loading boluses are continued until the patient is comfortable, the pain scale has decreased 50%, or the patient is sedated. This approach individualizes each loading regimen of opioid analgesics and avoids overtreatment of opioid-naive individuals and undertreatment of opioid-tolerant patients.

 

Table X: Opioid Agonist Analgesic Equivalents

Drug

Equianalgesic Doses*

Parenteral (mg)

Oral (mg)

Morphine

Levorphanol

Hydromorphone (Dilaudid)

Methadone

Meperidine (Demoral)

Codeine

Oxycodone (Percocet, Percodan)

10

2

1.5

10

75

130

N/A

60

4

7.5

20

300

200

30

*Based on acute short-term use. Chronic administration may alter pharmacokinetics and decrease the oral: parenteral dose ration. The morphine oral-parenteral ratio decreases to 3.0 upon chronic dosing.

Following the rapid relief of acute pain by the individualized loading procedure, the patient continues to control their pain by boluses of opioids at the same dosage employed for loading. The lockout interval is set at 6 minutes to permit the patient more rapid relief of pain. Continuous intravenous infusions are not employed during the day. It is re-enforced to the patient that they are in control of their pain management and can deliver 10 PCA doses each hour if needed. However, a portion (66%) of their daytime hourly opioid use by PCA is given as a continuous infusion from 10 p.m. to 8 a.m. to ensure adequate rest at night. The following day they resume control of their pain management by use of PCA boluses only.

A four hour cumulative opioid dose delivery limit may be set as a precaution until the staff become familiar with the PCA delivery system. However, if a continuous infusionis utilized, an appropriate allowance for PCA boluses must be permitted to void patient frustration if they trigger the PCA device without obtaining relief of their pain.

Appropriate dosing of analgesics utilizing PCA can be titrated by allowing each sickle cell patient to control their own pain. Conversion to either morphine or hydromorphone, and thus avoiding the risk of seizures due to the accumulation of normeperidine, can be facilitated by educating the patient about equivalent doses to allay fear or mistrust as this change occurs. Re-enforcing to the patient the total quantity of analgesic that they can self-administer if needed to relieve pain also transfers the control of their pain to the patient. Finally, negative interactions between the medical staff and patients regarding the control of opioids and judgements of the veracity of their pain by a second party can be avoided.

 

Table XI: treatment of Acute Sickle Cell Pain in the Hospital

Method B: Patient Controlled Analgesia (PCA)

Suggested Scheme for PCA in Treatment of Acute Sickle Cell Pain

1. Believe the patient.

2. Assess patient's perception of pain by employing a verbal pain scale (0-10).

3. Administer intravenous boluses of either morphine (2.5-10 mg) or hydromorphone (0.5-2 mg) every 10 minutes. Meperidine (10-25 mg) is used only in patients that are truly intolerant of morphine or hydromorphone.

4. Reassess the patient's perception of pain with the verbal pain scale after ten minutes. Continue to administer intravenous boluses every 10 minutes until either the pain scale is decreased 50%, the pain is relieved, or the patient is sedated. The total loading dose of opioid should be recorded to document tolerance to opioids to facilitate appropriate loading during the next episode of acute pain.

5. Begin pain controlled analgesia (PCA) by using 20% of the quantity of opioid bolus that was used in loading the patient to be delivered with a 6 minute lockout interval. Reassess the patient's perception of pain every 4-8h by using either a verbal or visual analogue pain scale.

6. Encourage the patient to control their own pain by reinforcing the quantity of opioid that they can deliver as needed and the equivalent potency when converting from meperidine to morphine or hydromorphone.

7. Determine the hourly use of opioid during the day and give 66% of the hourly dose as a continuous infusion at night to ensure rest.

8. On day 2 or 3 of hospitalization replace by an equivalent oral dose of opioid analgesic (preferably the same as the one used in PCA) on a fixed schedule around the clock and decrease the PCA dose by 25% every 24 hours.

9. After 24-48 hours, the PCA can be discontinued. Oral breakthrough doses can be administered between fixed doses of oral analgesics.

10. Patients may be ready for discharge if they are pain free or if their pain is adequately controlled with oral analgesics.

11. Taper the opioid after discharge over the following 1-2 weeks to prevent symptoms of the abstinence syndrome.

12. Resume control of chronic pain utilizing the 3 Step Analgesia Ladder if indicated.

D. Side Effects of Opioid Analgesics

All opioids have similar side-effects that can be anticipated Tables VI, VII). Prophylactic use of an antihistimine (hydroxyzine or diphenhydramine) can decrease pruritus in patients who have experienced this side-effect from morphine. Similarly, the empiric use of an anti-emetic (transdermal scopolamine or an oral phenothiazine) and a stool softener can obviate the nausea or constipation in patients who feel that these conditions justify the use of meperidine or mixed opioid analgesics (e.g., pentazocine).

Since each opioid may not produce cross-over of side-effects, trying a different opioid may lessen symptoms. Alternately, by changing the dosing regimen (e.g., decreasing the concentration of each intravenous bolus while shortening the time interval) side-effects may abate.

All patients should have naloxone readily available for treatment of respiratory depression. However, in contrast to the use of naloxone in the emergency room to quickly reverse a suspected drug-overdose, a dilute solution of naloxone (one ampule of 0.4 mg diluted with saline to 10 ml) should be available for titration. This solution should be administered at 0.5 ml IV q 2 minutes to avoid the precipitation of profound withdrawl, seizures, and severe pain (1).

VI. Non-Pharmacologic Management of Pain

Non-pharmacologic methods to treat pain have not been widely used in patients with sickle cell disease. Although such methods may not replace pharmacologic agents to treat pain in the majority of patients, nevertheless they are an important modality to achieve pain relief, reduce stress, and increase activity & normal function with reduced doses of opioid analgesics. Some patients with sickle cell disease have discovered on their own the beneficial effect of some of these modalities, such as diversional methods (e.g., watching TV, playing cards, etc.), self-motivation (e.g., setting goals to be achieved within a certain period), application of heating pads to painful areas of the body, massage, and mechanical stimulation.

Hospital personnel should understand the positive effects of such methods and encourage patients to use them. A patient who appears to be free of pain while watching TV or speaking on the telephone but whose pain appears to return when such diversional activities are interrupted is not a malingerer. Diversional activities may enable patients to reduce their requirement of opioid analgesics.

VII. Management of Pain in the Frequent Utilizers of Care Facilities (Difficult or "Problem" Patients)

Individuals with sickle cell disease who are felt to overutilize the hospital services create the most difficult management problems for both hospital staff and other patients with sickle cell disease. This group is the minority of those affected with sickle cell disease, yet they account for the majority of emergency department visits and hospital admissions. Because of this group of patients house staff have developed terms such as the "good sickler" or low utilizer as the "bad sickler" or high utilizer. In most cases high utilizer of services are equated with drug-seeking behavior. It is from this relatively small group of patients that the medical staff formulate their invalid opinions of drug-seeking behavior by patients with sickle cell disease. This stereotyping results in inadequate treatment of pain in other sickle cell disease patients.

Before addressing treatment options for this subset of patients, it should be emphasized that there is diversity within this subgroup itself. Understanding this diversity may be of help in formulating the most appropriate plan of management. Thus the "problem" patient may belong to any of the following subclasses:

A. Under Treatment:

These patients are not treated adequately for their pain as outpatients. Investigating and correcting this issue can change the pattern of service utilization in these patients.

B. Secondary Gain:

These patients rely on medical services because of social, financial, or psychological problems. They are often admitted but utilize minimal pain medication, while their other needs are being met.

C. Convenience:

These individuals find it easier to please the E.D. staff than to make and keep regular outpatient visits.

D. Drug Seeking:

This is the most difficult subclass of patients. Investigating these individuals may reveal prescription alteration or selling and/or substance abuse. Formulating a treatment plan should include intensive counseling, psychiatric evaluation, rehabilitation, and clear alignments with a drug rehabilitation unit.

Treatment contracts designed to set limits are perhaps the best method to deal with these patients (6). In addition to the patient, participants in the construction of a contract should include the following:

A. The individuals providing immediate social support for the patient (e.g., spouse, parents, children). Since pain due to sickle cell disease affects the entire family, family members should be involved in the development of a pain-treatment contract. These individuals can be instructed in the home management of pain as well as in behavioral modification techniques that the patient can employ to improve their coping with a chronic pain syndrome. In addition, expectations for treatment of pain in the emergency department and during hospitalizations can be solidified among the family involved at the inception of a contract.

B. Other patients with sickle cell disease or patient advocates within the community.

Some patients with sickle cell disease fail to realize that the care administered to other patients is affected by their behavior. By incorporating certain patients with the disease or person interested in the overall care of sickle cell patients at the writing of a pain management contract, patents that frequently utilize hospital services can begin to become involved in sickle cell and other community programs. These programs can provide social and recreational activities to improve a patient's ability to actively cope with pain. The involvement of selected patients or patient advocates also ensures that the care outlined in the contract is reasonable and not overly punitive.

C. The patient's primary physician. One physician must assume the primary responsibility for the patient's continuity of care both in and out of the hospital. This individual should be the focal point for pain management. As part of the contract, only this physician should write prescriptions for opioids to control pain. Ideally, only one pharmacy should be utilized to fill these prescriptions to ensure an accurate assessment of opioid use by the patient. Trust must develop among the physicians caring for the patient and the pharmacists filling the prescriptions that the patient is judiciously utilizing these medications.

D. A member of the medical staff of the emergency department where the patient is frequently seen. Just as one physician and ideally one pharmacy is involved in the dispension of opioids to control pain, the utilization of one hospital and one emergency department should be considered. Patients with pain due to sickle cell disease are infrequently admitted directly to the hospital. More commonly patients are initially evaluated in the emergency room where treatment of their pain is initiated. This medical staff should also be involved in writing the contract for a consistent plan of pain management.

The goals of such a contract should include relief of pain in patients with sickle cell disease. However, in some patients this must include the setting of strict limits within the context of a consistent plan for management of pain. The patient and his/her family should understand that the complaint of pain will be addressed. However, in addition to receiving opioids for treatment of pain, the importance of a consistent, co-ordinated plan that includes behavior modification and involvement in social support groups for patients with sickle cell disease are equally important.


Refererences

1. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer pain. 3rd Edition. American Pain Society. (Skokie, IL), 1993

2. Jacox AK, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice Guideline, No. 9 Rockville, MD: Agency for Health Care Policy and Research, 1994. AHCPR Publication No. 94-0592.)

3. Patient's Bill of Rights. In: Innovations in Pain Management. A Practical Guide for Clinicians. Weiner RS, Editor, Vol. 2: Appendx F. Paul M Deutsch Press, Orlando, 1993

4. Ballas SK: Treatment of pain in adults with sickle cell disease. Am J Hematol 34:49, 1990.

5. Ballas SK, Larner J, Smith ED, Schwartz E, Rappaport EF. Rheological predictors of the severity of the painful sickle cell crisis. Blood 72:1216, 1988.

6. Shapiro BS: Management of painful episodes in sickle cell disease. In Pain in Infants, Children, and Adolescents. Schecter NL, Berde CB, Yaster M (Eds.), Williams and Wilkins, Baltimore, MD, 1993.

7. Ballas S, Delengowski A: Pain management in hospitalized adults with sickle cell painful episodes. Annals Clin Lab Sci 23:358, 1993.

8. Walco GA, Dampier CD: Pain in children and adolescents with sickle cell disease. J Pediatric Psychol 5:643, 1990.

9. Gil KM: Coping with sickle cell disease pain. Annals of Behavioral Medicine 11:49, 1989.

10. Tobin DL, Holroyd KA, Reynolds RV, Wigal JK: The hierarchical factor structure of the Coping Strategies Inventory. Cognit Ther Res 13:343, 1989.

11. McGrath PA, Pain in Children: Nature, Assessment, Treatment. Guilford Press, New York, 1990.

12. Platt OS, Thorington BD, Brambila DJ, Milner PE, Ross WF, Vichinsky E, Kinney TR: Pain in sickle cell disease. Rates and risk factors. New Engl J Med 325:11, 1991.

13. Shapiro BS, Dinges DF, Carota-Orne E, et al:Recording of crisis pain in sickle cell disease. In:Advances in Pain Research and Therapy. Tyler DC, Krane EJ (Eds.), pp 313-321, Raven Press, New York,

14. Weisman SJ, Schechter NL: Sickle cell anemia: pain management: In: Acute Pain: Mechanisims and Management. Sinatra RS, Hord AH, Ginsberg B, Preble LM (Eds). Mosby Year Book, St. Louis.

15. Cancer Pain Relief. Geneva: World Health Organization 1986

16. Achord JL: Gastroenterologic and hepatobiliary manifestations. In Sickle Cell Disease: Basic Principles and Clinical Practice. Embury SH, Hebbel RP, Mohandas N, Steinberg MH (Eds.) Raven Press, Ltd., New York, 1994, pp 665-666.

17. Falk RJ. Jeannette JC: Renal Disease. In: Sickle Cell Disease: Basic Principles and Clinical Practice. Embury SH, Hebbel RP, Mohandas N, Steinberg MH, (Eds). Raven Press, Ltd., New York, 1994, pp 677. techniques. Ann NY Acad Sci 565:189, 1989

19. Tang R, Shimomura SK, Rotblatt M: Meperidine-induced seizures in sickle cell patients. Hosp Formul 764, 1980.

20. Liu JE, Gzesh DJ, Ballas SK: The spectrum of epilepsy in sickle cell anemia. J Neurological Sciences 123:6, 1994.

21. Nadvi S, Sarnaik S, Ravindranath Y: Association of seizures with meperidine in sickle cell disease. 20th Meeting of the National Sickle Cell Program, Boston, MA, March 18-21, 1995, Book of Abstracts p 210, 1995 (Abstract).

22. Benedetti C, Butler SH: Systematic analgesics. In: The Management of Pain, 2nd Edition. Bonica JJ (Ed). Lea & Febiger, Philadelphia, PA, 1990, p 1651.

23. Cantees K, Dunwoody C, Carlos T, Stacey B: Promoting active patient participation in management of pain crisis utilizing patient controlled analgesia (PCA). 20th Meeting of the National Sickle Cell Program, Boston, MA, March 18-21, 1995, Book of Abstracts p 140, 1995 (Abstract).