Additional Material

The Problem

• Pain due to vaso-occlusive episodes is prevalent in patients with Sickle Cell Disease (SCD)
• Numerous chronic complications associated with SCD makes provision of quality care complex
• Documented racial disparities in care exist for black patients, the population most frequently exhibiting the SCD phenotype
• Racial minorities and persons of lower socioeconomic means may be negatively stereotyped when presenting for care of pain symptoms
• Black children with SCD are at risk for “lost to followup” when transitioning from pediatric to adult primary care.

The Solution

• Recognition of the prevalent nature of acute and chronic pain experienced by patients with SCD
• Interdisciplinary team approach to health care and case management for patients with SCD to prevent acute pain episodes, infection, and vaso-occlusive complications
• Application of standardized treatment protocols and individualized care plans for patients with SCD to reduce the risk of disparate care
• Development of health system polices to ensure all patients, regardless of race or ethnicity, are treated compassionately and equally when risk or overt signs of aberrant drug taking behavior is identified

What is Sickle Cell Disease?

SCD is an inherited disorder characterized by a genetic predisposition for hemoglobin abnormalities (hemoglobin S) which results in deformed red blood cells (RBCs)
The deformed red blood cells are unable to travel normally through the vasculature (microvascular occlusion or “vaso-occlusion”) and undergo hemolysis earlier than their normal RBC counterparts which results in numerous complications.

1. SCD anemia is typically characterized as chronic and reasonably well compensated.  Sickled red blood cells possess an average life span of 17 days compared to 120 days in a person without SCD or a related hemoglobinopathy.  Average hemoglobin and hematocrits reported in large observational studies are 7.9 g/dL and 22.9%, respectively.  Stem cells are oftentimes able to “keep up” with the early hemolysis of RBCs and a resultant reticulocytosis prevents overt hypoxia.  Severe drops in hemoglobin may present during splenic sequestration crisis, aplastic crisis, and hyperhemolytic crisis, all of which are possible in the patient with SCD.
2. Children with SCD are at significant risk for morbidity and mortality due to infection.  Infection may be due to the spleen’s inability to appropriately remove pathogenic micro-organisms due to RBC sickling and a faulty immunoglobulin response to infection.  In fact, recommendations exist to prophylactically treat all children with SCD with penicillin or a similar antibiotic to prevent Streptococcus-associated bacteremia at least until five years of age.
3. Splenic sequestration refers to the development of an enlarged and often tender spleen on palpation due to “trapping” of the deformed RBCs as well as white blood cells.  Patients with splenic sequestration may present with an acute drop in hemoglobin concentration, platelet counts, and a drastically increased production of immature RBCs.  Most concerning with splenic sequestration is the risk for hypovolemic shock due to the sheer quantity of intravascular blood held within the spleen.
4. While acute pain in SCD is fairly straight forward, specific criteria from the Cooperative Study for Sickle Cell Disease suggests that an acute pain episode attributed to SCD  be located in the extremities, back, abdomen, chest, or head for a duration of at least two hours and results in the patient accessing care either in the clinic or being hospitalized.  Prevalence of pain appears to grow as the patient with SCD ages.  Studies suggest that as many as 1/3 of patients with SCD experienced either acute or chronic pain 95% of the time. This corresponds with other study results showing 33% of patients with SCD will be hospitalized six or more times annually due to acute pain symptoms. Goals of treatment focus on alleviation of symptoms and prevention of future acute pain episodes.  The drug hydroxyurea, which changes the expression of hemoglobin subtype, has been shown to reduce hospitalizations due to acute pain episodes associated with vaso-occlusion in SCD.
5. Chronic pain in patients with SCD is less well understood.  Based on a prospective cohort study, just under 30% of patients with SCD reported pain greater than 95% of the time, with an unpredictable waxing and waining nature.  Some have described this as “acute on chronic pain” however this term is not universally recognized.  Chronic pain associated with SCD may be due to a multitude of factors including extremity ulcers, avascular necrosis, and hypoxia related nerve injury (neuropathic mediated pain).  Regardless of the etiology or association, chronic pain should be addressed aggressively with interdisciplinary and multi-modal treatment.
6. Acute chest syndrome, characterized by chest radiograph changes, fever, and respiratory symptoms, is the leading cause of death among patients with SCD.  Incidence is greater in younger patients while severity and mortality increases with age.  As many as 50% of persons with SCD will have experienced acute chest syndrome sometime during their lives.

Complications Associated with Sickle Cell Disease

1. Hemolytic anemia
2. Increased risk of infection
3. Splenic sequestration
4. Acute pain episodes due to vaso-occlusion
5. Chronic pain
6. Acute chest syndrome

Vaso-occlusive Acute Pain Episode Triggers

Trigger avoidance is critically important in preventing acute pain episodes in patients with SCD.  The following triggers have been associated with acute pain in patients with SCD:

• Weather conditions
• Environmental pollutants
• Dehydration
• Infection
• Stress
• Menses
• Alcohol
• Obstructive / Central Sleep Apnea

Summarized Recommendations from the National Institute for Health and Clinic Excellence (NICE) Sickle Cell Acute Painful Episode Management Guidelines

1. Acute painful episodes associated with SCD should be managed as a medical emergency
2. Consider the patient and / or their caregiver as an “expert” in their medication condition:
   • Present your planned course of treatment
   • Discuss treatments that worked or did not work during previous acute painful episodes
   • Request from the patient concerns they may have about this particular episode
   • Specifically query patient about mental health or social support needs they may have
3. Assess pain at presentation using an age-appropriate scoring tool
4. Offer analgesia within 30 minutes of presentation
   • Specifically ask about analgesics taken by patient for this episode prior to presentation
   • Ensure the right drug, given via the right route, at the right dose is employed
   • Refer to individual care plan, if available
5. Closely monitor blood pressure, oxygen saturation, heart rate, respiratory rate, temperature
6. Rule out other possible causes of pain with close attention paid to patient’s claims that pain is atypical compared to previous episodes (specifically stroke, aplastic crisis, infection, osteomyelitis, or splenic sequestration)
7. Assess for possible acute complications you just learned about
8. Prior to discharge care-planning and education should include:
   • Obtaining specialist support
   • How to obtain additional medication, if required
   • How to manage potential side effects of the treatments already received

Reference

National Institute for Health and Clinical Excellence (NICE). Sickle cell acute painful episode: management of an acute painful sickle cell episode in hospital. London (UK): National Institute for Health and Clinical Excellence (NICE); 2012 Jun. 25 p. (NICE clinical guideline; no. 143).

Specific Analgesic Treatment Considerations from the National Institute for Health and Clinic Excellence (NICE) Sickle Cell Acute Painful Episode Management Guidelines

1. As early as possible, provide an intravenous bolus dose of a strong opioid (i.e. morphine, hydromorphone, or fentanyl) 
   • In all patients presenting with severe pain
   • In patients with moderate pain despite self-medication with analgesics prior to presentation
   • Meperidine (Demerol) should be avoided
2. All patients should be provided acetaminophen and a non-steroidal anti-inflammatory drug (NSAID) unless contraindicated
   • Corticosteroids (i.e. prednisone, methylprednisolone, dexamethasone) should be avoided in uncomplicated acute pain episodes
   • Avoid NSAIDs in pregnant patients
3. Reassess pain, using an age-appropriate tool, every 30 minutes until adequate analgesia is achieved, then every hour for opioid-associated side effects and every four hours for pain severity
4. If repeated intravenous bolus doses of strong opioids are required within two hours, considered patient controlled analgesia using demand dosing only in opioid naïve patients
5. Encourage or teach non-pharmacologic modalities (i.e. relaxation, breathing, guided imagery)
6. All patients receiving opioids should additionally be offered stimulant laxatives, anti-emetics, and anti-pruritics

A treatment algorithm based on the guidelines is freely available here.

Patient controlled analgesia, while usually referring to an intravenous pump, is the provision of direct control over analgesic dosing to the patient.  Using specially equipped intravenous pumps, patients are provided a control device (a button to push) to deliver a pre-determined dose of analgesic medication.

Opioid naïve refers to the history of medication use immediately leading up to the presenting acute pain episode.  Generally patients are considered opioid naïve if they have been using opioid analgesics for less than seven days with regularly dosing or have been using less than 60 milligrams of oral morphine or an equivalent dose of another opioid analgesic. While some variance in “equivalent doses” exists, in general 60 milligrams of oral morphine = 60 milligrams of oral hydrocodone = 40 milligrams of oral oxycodone = 20 milligrams of oral oxymorphone = 12 milligrams of oral hydromorphone

Reference

National Institute for Health and Clinical Excellence (NICE). Sickle cell acute painful episode: management of an acute painful sickle cell episode in hospital. London (UK): National Institute for Health and Clinical Excellence (NICE); 2012 Jun. 25 p. (NICE clinical guideline; no. 143).

Managing the Risk of Prescribing Opioids

Opioid analgesics are important in the treatment of acute pain episodes associated with SCD.  There are risks associated with these medications and patients with substance abuse problems or criminal intent may “fake” pain in order to obtain them.  Strategies exist to reduce this risk:

1. Clearly outlining expectations of the patient via a signed treatment agreement
2. Urine, saliva, or blood drug screens to identify problematic use or illicit substances 
3. Prescription drug monitoring programs
4. Risk assessment tools

Examples of Frequently Used Risk Assessment Tools to Predict Problematic Opioid Use

(Note: the COMM risk assessment tool is validated only in patients already using opioid analgesics)

^α  SOAPP®-R (Screener and Opioid Assessment for Patient’s in Pain-revised); DIRE (Diagnosis, Intractability, Risk, and Efficacy); ORT (Webster’s Opioid Risk Tool); COMM (Current Opioid Misuse Measure); CAGE (Cut-down, Annoyed, Guilt, Eye-opener)

Common Definitions of Problematic Medication or Illicit Drug Use

Aberrant Drug Taking Behavior

"Any medication-related behaviors that depart from strict adherence to the prescribed plan of care.”

Addiction

A neurobiologic disorder manifesting lack of control or impulsivity associated with ongoing use of a substance despite known physical, professional, or social detrimental effects.

Misuse

“The use of medication, with therapeutic intent,  other than as directed or indicated, whether willful or unintentional, whether harm results or not.”

Abuse

“Any use of an illegal drug or the intentional self-administration of a medication for a nonmedical purpose such as altering one’s state of consciousness…”

Diversion

The act of obtaining prescription medications by feigning an illness or disease, and subsequently distributing the medication to others.

Tolerance

“A state of adaptation in which exposure to a given dose of drug induces biologic changes that result in diminution of 1 or more the drug’s effects over time.”  Escalating doses are required to maintain a consistent effect.

Dependence

“The state of pharmacological adaptation manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level, or administration of an antagonist.”

Pseudoaddiction

“A condition in which patients with undertreated pain exhibit certain aberrant behaviors in an attempt to obtain adequate management of their pain.”

Interpretations of Drug Screens

Drug screens are frequently ordered when patients are considered at high risk for aberrant drug taking behaviors.  It is the opinion of these authors that opioid analgesics should not be withheld from patients presenting for SCD acute pain episodes while awaiting drug screen results.  

The most commonly used drug screen is from the patient’s urine.  A general rule of thumb is the quicker you receive the results from a drug screen, the less accurate the results are.  Confirming results by sending the urine sample to a laboratory for advanced analysis is always recommended.  A common problem once results are received is how to interpret them.

Consider this: the body metabolizes most drugs to metabolites.  Some of these metabolites may show up in a urine drug screen report.  You should expect to find these metabolites, which sometimes may be other drugs you’re familiar with.  Some common examples:

• Codeine is metabolized to morphine
• Hydrocoone is metabolized to hydromorphone
• Oxycodone is metabolized to oxymorphone

Test Your Knowledge

A patient with SCD presents to your emergency department with severe pain due to an acute pain episode.  A urine drug screen result from the last visit shows  both  codeine AND morphine.  The patient should only be taking codeine.  Should this be considered a sign of an aberrant drug taking behavior?

Racial and Ethnic Disparities in Health Care Services

Unfortunately the heathcare received by patients of various racial and ethnic minorities may differ from care received from non-minority patients.  This is tragic, but has been well-documented.  

Racial / Ethnic disparities in care have been identified in the following health care scenarios:

• Orthopedic / neurosurgery referral for low back pain
• Angioplasty following acute coronary syndrome
• Opioids received in the emergency department setting
• Dose of analgesic prescribed by male primary care physicians 
• Receipt of ACIP / CDC recommended vaccinations
• Receipt of preventive dental sealants to prevent caries
• Smoking cessation guidance / education
• Receipt of chemotherapy for early breast cancer
• Substance abuse treatment program referral and completion

References

• Institute of Medicine, Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care (Washington, D.C.: National Academy of Sciences, 2003).
•  H. Mead, L. Cartwright-Smith, K. Jones, C. Ramos, K. Woods, and B. Siegel, Racial and Ethnic Disparities in U.S. Health Care: A Chartbook, The Commonwealth Fund, March 2008.

Test Your Knowledge

Question 1

What percentage of patients with SCD are hospitalized six or more times each year (Choose 1)

Question 2

Racial / Ethnic disparities in care have been identified in which of the following health care scenarios (there may be more than one correct answer)

Question 3

Only patients who are black can carry the sickle cell disease gene.

Question 4

Which of the following treatment regimens represents guideline based recommendations for the treatment of an acute pain episode related to vaso-occlusive SCD?

Question 5

Which of the following have been identified as risk factors or triggers for acute pain episodes due to SCD? (There may be more than one correct answer.)

Question 6

Which of the patient variables below are risk factors for opioid misuse ? (There may be more than one correct answer.)