Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 1

Revised: October 7, 2020

Prescribing Guidelines for Pennsylvania

TREATMENT OF ACUTE AND CHRONIC

PAIN IN PATIENTS WITH

SICKLE CELL DISEASE

ickle cell disease (SCD) ) is the most common associated with milder symptoms. There are also some S inherited blood disorder.1 In the United States less common variants with different degrees of severity. approximately 100,000 Americans have sickle HbS/hereditary persistence of fetal hemoglobin rarely cell disease. There are several different forms of SCD, causes symptoms due to the high level of fetal Hb. with homozygous SCD (HbSS) and Sβ0 thalassemia Sickle cell trait (HbAS) is a benign carrier state, not a being the most severe, accounting for about 70% of chronic disease, but can become symptomatic under cases. Other forms include hemoglobin Sβ+ conditions of significant hypoxia. thalassemia and hemoglobin SC, which is usually

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 2

Pain from SCD can present as acute, chronic, or a nervous system sensitization, and adversely impact pain mixture of acute and chronic pain.2 Recurrent episodes treatment efforts.6 Some SCD patients may develop of acute, severe pain is common in patients with SCD. hyperalgesia, which can impact treatment of both acute The acute pain experience associated with SCD is highly and chronic pain states.7 Many SCD patients often variable, both between patients and between episodes experience depression and anxiety. Chronic pain, within the same patient. Acute pain episodes often recurrent episodes of acute pain, fatigue and negative occur spontaneously, but they can be caused by certain encounters with medical professionals8, 9 may be triggers such as other painful events, infection, contributing factors. Treatment of depression and dehydration, exposure to extreme and/or sudden anxiety through the use of medications, self- changes in temperature and stress. While most acute management programs and/or cognitive-behavioral episodes can be treated in the home setting, patients therapy can improve symptom burden and may may seek pain care in the emergency department (ED) improve pain severity, frequency and duration.10 setting when the episodes are not responsive to home Multimodal pain care may lessen symptom burden in treatment and may require admission for further SCD patients experiencing chronic pain. One study evaluation and pain control. Upon discharge, the suggests that long-term use of opioids for the treatment patient should be referred to their primary care of chronic pain in patients with SCD is not associated provider and/or to the outpatient prescriber of their with improved outcomes, as patient-reported pain pain medication. intensity and physical functioning is often not

It is important to note that SCD patients with acute improved.11 However, long-term use of opioids for the painful crises often experience significant delays in treatment of chronic pain in patients with SCD has not receiving pain treatment,3 and their pain is often been carefully studied. An assessment of the patient’s inadequately treated.4 response to treatment, including pain relief, side effects, and functional outcomes, should guide long- Patients with SCD may also develop chronic pain, which term use of opioids.12 adversely impacts physical and mental functioning and overall quality of life. About 30% of adult patients with These guidelines are intended to provide best practices SCD report experiencing pain over 50% of the time.5 It related to the treatment of acute and chronic pain in is important to note that repeated episodes of acute patients with SCD. They are intended to help pain, which is commonplace in patients with SCD, can healthcare providers improve patient outcomes and to lead to the development of peripheral and central supplement, but not replace, the individual provider’s

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 3

clinical judgment. It is recommended that providers enlargement, abdominal crisis and neurological review other evidence-based guidelines for Sickle Cell events (including transient ischemic attack or Disease, such as the National Institutes of Health 2014 stroke).1 Expert Panel Report: Evidence-Based Manage of Sickle 3. When patients are presenting for care in the ED Cell Disease.12 The American Society of Hematology has setting with severe pain, initial patient also released clinical practice guidelines for SCD and is evaluation should be completed, and patients currently in the progress of creating more13. The should receive pain treatment as quickly as Pennsylvania State Guidelines related to the use of possible.12 In general, analgesic treatment opioids to treat pain in a variety of patient populations should not be withheld pending lab work and treatment settings provide insight into treatment and/or detailed evaluation for common options for other patient populations.

associated conditions. Acute Painful Crises 4. Optimal outcomes may be achieved through 1. Patients and their families should be educated the use of a standardized process in the ED for on possible triggers and options to help patient evaluation, rapid institution of pain decrease the frequency of acute painful crises therapy, and IV hydration. Patients should be and methods for immediate treatment when triaged as a high priority.12 they occur. Patients and their family should be educated on when to seek further evaluation 5. Scheduled acetaminophen should be continued and treatment, often when oral analgesia has or administered when not contra-indicated. not been effective in controlling pain. This can 6. Scheduled non-steroidal anti-inflammatory include a process to receive timely care in the drugs (NSAIDs) should be continued or ED or an infusion center, or an established administered when not contra-indicated. process to receive inpatient admission for

14 further evaluation and treatment. 7. Outpatient providers of patients with SCD should consider hydroxyurea treatment to 2. Patients presenting with acute painful crises decrease the frequency of acute painful crises. should be evaluated for possible common Hydroxyurea treatment improves survival in associated conditions, including infection, patients with SCD and decreases the number of dehydration, hypovolemia, acute chest acute painful crises experienced per year. syndrome, severe anemia, cholecystitis, splenic

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 4

However, hydroxyurea treatment does not be individualized for patients to effectively treat existing pain. optimize patient outcomes.

8. Opioids are often necessary for the treatment c. Pain care in the ED setting often is of acute painful crises in SCD patients. started with the use of IV opioids. Although opioids should be used in the lowest When IV access is difficult, alternative effective dose for the shortest duration routes should be considered. It is possible, patients with acute painful crises may important to note that though there are require aggressive initial opioid doses to situations when IV push opioid achieve adequate pain control. administration is necessary, there is growing concern that this delivery a. SCD patients should have an method may increase risk of opioid established protocol for the use of oral misuse, abuse, and addiction.23 opioids in the home setting to lessen

the frequency of ED visits or d. Patients requiring inpatient treatment hospitalization. Individualized patient may benefit from IV patient-controlled protocols should be used to help guide analgesia (IV PCA). IV PCA appears to pain treatment in the ED and inpatient be most effective when pain control is settings. This may reduce the need for achieved first via IV bolus long-term outpatient opioid use.15 If a administration16-18 (please see caution patient does not have a pain above). PCA should begin in the ED management plan for the home setting, when possible and once admitted if not they should be referred to their initiated in the ED.12 appropriate outpatient provider to e. Centrally acting sedatives, including establish one. benzodiazepines and Z-drugs, should

b. When presenting for acute painful not be administered concurrently with crisis, patients should undergo rapid potent opioids. Patients should be clinical assessment followed by pain educated on the risk of respiratory treatment as quickly as possible.12 depression and potential death if both When possible, institutions should are combined. establish a standard protocol that can

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 5

f. Short-term opioids may be necessary at self-management techniques for chronic the time of discharge.19 However, upon pain.20,21 discharge, the patient should be 4. Clinicians should be mindful of intrinsic biases referred to their primary care provider that may be contributing to racial disparities in and/or to the outpatient prescriber of pain management for patients with sickle cell their pain medication to evaluate the disease. Clinicians should also use caution to current opioid dosage and tapering avoid stigmatizing language in the medical chart plan.

as this may contribute further to biases in Chronic pain care treatment.

1. Patients with SCD who have chronic pain should 5. Occupational therapy can have a direct undergo a comprehensive evaluation for the therapeutic impact on the physiological underlying cause(s) of the pain. The evaluation structures and psychosocial experiences that may need to be completed by a pain specialist cause pain by modifying postures, positions, or in collaboration with the patient’s hematologist activities that cause stress; designing custom and/or primary care provider. orthotics or adaptive equipment to improve

a. The evaluation should be comprehensive participation; and implementing sensory and include an assessment of pain, mood strategies and mind-body connection (including an assessment for depression and techniques to decrease the impact of acute anxiety), sleep and physical functioning. anxiety and other psychosocial comorbidities of pain. 2. Chronic pain care should be interdisciplinary in nature and include use of non-opioid 6. There is growing concern that the use of chronic medications and techniques such as physical opioids in patients with SCD may not improve therapy, cognitive behavioral therapy, deep pain outcomes. Patients with SCD who have tissue/deep pressure massage therapy, muscle developed hyperalgesia may not benefit from relaxation therapy, osteopathic manipulative long-term use of opioids and the use of long- therapy and self-hypnosis as indicated. term opioids, especially at high daily doses, may worsen it. When starting chronic opioid 3. Evaluation and treatment by a pain psychologist therapy, the clinician should discuss the risks may be helpful for educating patients on proper and potential benefits associated with

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 6

treatment, so that the patient can make an to their insurance carrier or the informed decision regarding treatment. Department of Drug and Reasonable goals and expectations for Alcohol Programs Get Help Line treatment should be agreed upon, and the at 1-800-662-4357 (HELP) or patient should understand the process for how www.DDAP.PA.GOV. the care will be provided. b. Patients who would like to taper off

a. Patients receiving long-term opioid long-term opioid therapy should speak therapy should be cared for in with their provider to develop an accordance with established clinical individualized tapering plan. Patients treatment guidelines on the use of with SCD undergoing an opioid taper opioids for the treatment of chronic are likely to require a slow taper over noncancer pain in patients with SCD.12 an extended period of time.

i. In patients who have engaged i. Providers should review the in aberrant drug-related risks and benefits of the current behaviors, clinicians should therapy with the patient and carefully determine if the risks check the patient’s Prescription associated with long-term Drug Monitoring Program opioid therapy outweigh (PDMP), as required by Act 191 document benefit. Clinicians of 2014, to help determine if should consider restructuring tapering of opioids is therapy (frequency or intensity appropriate based on individual of monitoring), referral for circumstances. Providers can assistance in management, or review the Health and Human discontinuation of long-term Services Guide for Clinicians on opioid therapy. Appropriate the Appropriate Dosage referral for substance use Reduction or Discontinuation of disorder evaluation and Long-Term Opioid Analgesics treatment should be provided. for further guidance.22 A clinician may refer the patient

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 7

References 13. American Society of Hematology. ASH Clinical Practice Guidelines on Sickle Cell Disease. 2019; 1. Rees DC, Olujohungbe AD, Parker NE, et al. Accessed February 13, 2020 at Guidelines for the management of the acute painful https://www.hematology.org/SCDguidelines/ crisis in sickle cell disease. Br J Haematol. 14. Fertleman CR, Gallagher A, Rossiter MA. Evaluation 2003;120(5):744-752 of fast track admission policy for children with sickle 2. Okpala I, Tawil A. Management of pain in sickle-cell cell crises: questionnaire survey of parents’ disease. J R Soc Med. 2002;95(9):456-458. preferences. BMJ. 1997;315(7109):650. 3. Haywood, C, Tanabe P, Naik R, Beach MC, Lanzkron 15. Jacobson SJ, Kopecky EA, Joshi P, Babul N. S. The impact of race and disease on sickle cell Randomised trial of oral morphine for painful patient wait times in the emergency department. episodes of sickle-cell disease in children. Lancet. Am J Emerg Med. 2013;31(4):651-656. 1997;350(9088):1358-1361. 4. Wilson BH, Nelson J. Sickel cell disease pain 16. Holbrook CT. Patient-controlled analgesia pain management in adolescents: a literature review. management for children with sickle cell disease. J Pain Manag Nurs. 2015;16(2):146-151. Assoc Acad Minor Phys. 1990;1(3):93-96. 5. Smith WR, Penberthy LT, Bovbjerg VE, et al. Daily 17. McPherson E, Perlin E, Finke H, Castro O, Pittman J. assessment of pain in adults with sickle cell disease. Patient-controlled analgesia in patients with sickle Ann Intern Med. 2008;148(2):94-101. cell vaso-occlusive crisis. Am J Med Sci. 6. Aich A, Jones MK, Gupta K. Pain and sickle cell 1990;299(1):10-12. disease. Curr Opin Hematol. 2019;26(3):131-138. 18. Shapiro BS, Cohen DE, Howe CJ. Patient-controlled 7. Campbell CM, Moscou-Jackson G, Carroll CP, et al. analgesia for sickle-cell-related pain. J Pain Symptom An Evaluation of Central Sensitization in Patients Manage. 1993;8(1):22-28. with Sickle Cell Disease. J Pain. 2016;17(5):617-627. 19. Pennsylvania Department of Health. Commonwealth 8. Shapiro BS, Lennette BJ, Payne R, et al. Sickle cell- of Pennsylvania Laws Surrounding Controlled related pain: Perceptions of medical practitioners. J Substances. 2017; Accessed December 16, 2019 at Pain Symptom Manage.1997;14(3):168-174. https://www.health.pa.gov/topics/Documents/Progr 9. Haywood, C, Tanabe P, Naik R, et al. The impact of ams/PDMP/4-PDMP_PA_Laws_FactSheet_F.pdf. race and disease on sickle cell patient wait times in 20. Thomas V. Cognitive behavioural therapy in pain the emergency department. Am J Emerg Med. management for sickle cell disease. Int J Palliat Nurs. 2013;31(4):651-656. 2000;6(9):434-442. 10. Toumi ML, Merzoug S, Boulassel MR. Does sickle cell 21. Thomas VJ, Gruen R, Shu S. Cognitive-behavioural disease have a psychosomatic component? A therapy for the management of sickle cell disease particular focus on anxiety and depression. Life Sci. pain: Identification and assessment of costs. Ethn 2018;210:96-105. Health. 2001;6(1):59-67. 11. Carroll CP, Lanzkron S, Haywood C, et al. Chronic 22. Dowell D, Jones C, Compton W, et al. U.S. Opioid Therapy and Central Sensitization in Sickle Department of Health and Human Services Guide for Cell Disease. Am J Prev Med. 2016;51(1 Suppl 1):S69- Clinicians on the Appropriate Dosage Reduction or 77. Discontinuation of Long-Term Opioid Analgesics. 12. National Heart Lung and Blood Institute. Evidence- Accessed December 16, 2019 from Based Management of Sickle Cell Disease. Expert https://www.hhs.gov/opioids/sites/default/files/201 Panel Report. 2014; Accessed December 16, 2019 9-10/Dosage_Reduction_Discontinuation.pdf. from https://www.nhlbi.nih.gov/sites/default/ 23. Herzig SJ, Mosher HJ, Calcaterra SL, Jena AB, Nuckols files/media/docs/sickle-cell-disease- TK. Improving the safety of opioid use for acute report%200208160.pdf. noncancer pain in hospitalized adults: a consensus

Guidelines for Treatment of Acute and Chronic Pain in Patients with Sickle Cell Disease | 8

statement from the Society of Hospital Medicine. J Hosp Med. 2018;13(4):263-271. Accessed July 3, 2020 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC627 8928/

Authors Michael Ashburn, MD, MPH, University of Pennsylvania Sarah Boateng, MHA, PA Department of Health Maureen A. Cleaver, PA Department of Drug & Alcohol Programs Rubye Jenkins-Husband, M.S., UNFHCC Sickle Cell Program Rachel Levine, MD, Secretary of Health, PA Department of Health Meghna Patel, MHA, PA Department of Health Gwendolyn Poles, DO, Retired, UPMC Pinnacle Robin Rothermel, Pennsylvania Medical Society Emily Roussel, MPH, PA Department of Health Kim Smith-Whitley, MD, Children’s Hospital of Philadelphia Dominique Stevens-Young, MSW, LCSW, Serenity Life Management Group