Sickle Cell Disease Management of Acute and Chronic Pain

Publication Date: June 1, 2020
Last Updated: March 14, 2022

Recommendations

For adults and children with SCD presenting to an acute care setting with acute pain related to SCD, the ASH guideline panel recommends rapid (within 1 hour of emergency department [ED] arrival) assessment and administration of analgesia with frequent reassessments (every 30-60 minutes) to optimize pain control. (StrongLow)
607

For adults and children with SCD presenting to an acute care setting with acute pain related to SCD for whom opioid therapy is indicated, the ASH guideline panel suggests tailored opioid dosing based on consideration of baseline opioid therapy and prior effective therapy
  • for adults
(ConditionalModerate)
607
  • for children
(ConditionalLow)
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Remarks:

  • Individualized care plans, developed with acute care and SCD care providers, are treatment recommendations that include medications and doses that are effective for a given patient. These plans can be embedded in the electronic medical record and used to guide opioid dosing.

  • For a minority of patients, frequent acute care treatment using individualized opioid dosing may be ineffective and detrimental to long-term care goals, and a more chronic care paradigm with other approaches may be needed.

  • Patient preferences for acute-pain management should be incorporated into the shared decision-making process, and patient education on limitations and harms of opioid therapy should be included in the discussion.

  • Adequate clinical infrastructure, including appropriate patient records, means of communicating between sites of care, and a multidisciplinary team with appropriate skills, is needed to create appropriate care plans.


Nonopioid pharmacological therapies

For adults and children with acute pain related to SCD, the ASH guideline panel suggests a short course (5 to 7 days) of nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to opioids for acute pain management. (ConditionalVery Low)

Remarks:

  • NSAIDs herein are defined broadly to include selective and nonselective cyclooxygenase (COX) inhibitors.

  • Patient-specific assessment of harms, including but not limited to renal, vascular, and gastrointestinal toxicity, anticoagulation requirements, and cardiovascular disease, will help identify patients who are appropriate for NSAID therapy and tailor the selection of the drug/class of NSAID based on this risk profile.

  • Patients specifically at increased risk of renal toxicity need to be identified. If comorbidities (eg, peptic ulcer disease, renal dysfunction, full-dose anticoagulation) are a significant risk factor, the mild potential benefit may not outweigh the risk.

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It is good practice to provide patient-centered education and surveillance related to NSAID toxicity, especially in patients with end-organ comorbidities, because long-term safety data for SCD are lacking, but vascular, bleeding, and renal risks may be elevated. (, )
(Good practice statement)
607
For adults and children presenting for acute pain related to SCD, the ASH guideline panel suggests against corticosteroids for acute pain management. (ConditionalLow)

Remarks:

  • Steroids should still be used when appropriate for the treatment of other medical indications such as asthma.

  • Systemic corticosteroid exposure, particularly cessation of steroids, has been associated with rebound pain and other complications; therefore, the decision to use steroids for other medical indications should be made in collaboration with experts in SCD.

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For adults and children presenting with acute pain related to SCD who are hospitalized, the ASH guideline panel suggests a subanesthetic (analgesic) ketamine infusion as adjunctive treatment of pain that is refractory or not effectively treated with opioids alone (ConditionalVery Low)

Remarks:

  • This recommendation assumes safe administration of subanesthetic ketamine infusions in the hospital inpatient unit in centers that have appropriate expertise to administer the drug.

  • Recommended dose for subanesthetic (analgesic) infusion for acute exacerbation of SCD pain starts at 0.1 to 0.3 mg/kg per hour with a maximum of 1 mg/kg per hour.

  • Currently, there is no standardized, widely accepted definition for the word refractory; therefore, whether pain is considered refractory is determined at the clinician’s discretion.

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For adults and children presenting with acute pain related to SCD, the ASH guideline panel suggests regional anesthesia treatment approaches for localized pain that is refractory or not effectively treated with opioids alone. (ConditionalVery Low)

Remarks:

  • Regional anesthesia in this context is defined as epidural or peripheral nerve catheter-delivered analgesia for abdominal, hip, or leg pain.

  • The procedure needs to be technically feasible based on the anatomical location of the pain.

  • A thorough explanation of the procedure as well as risks, benefits, and alternative options should be provided to patients and families before the procedure.

  • The recommendation assumes administration of the procedure in a center that has appropriate resources and expertise.

  • There is considerable uncertainty around optimal timing and indications for regional anesthesia interventions; however, the panel emphasized the importance of shared decision making based on the patient’s knowledge of his or her own disease and course of pain-related complications and strategies that promote reduced opioid requirements, improved function, pain management, and reduced duration of hospitalization.

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For adults and children who seek treatment of acute pain, the ASH guideline panel chooses not to offer a recommendation for or against IV fluids in addition to standard pharmacological management for the treatment of acute pain. (, )

Remarks:

  • The panel acknowledges that the risk of harm with IV fluids may be greater in adults than children because of deficiencies in cardiopulmonary function and other comorbid conditions.

  • This nonrecommendation includes bolus infusions and infusions to maintain fluid balance requirements in addition to the types of fluids (eg, normal [0.9%] saline vs half-normal [0.45%] saline) that are used in these infusions.

  • This nonrecommendation does not preclude the administration of fluids to patients with clinically significant dehydration.

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Nonpharmacological therapies

For adults and children who seek treatment of acute pain, the ASH guideline panel suggests massage, yoga, transcutaneous electrical nerve stimulation (TENS), virtual reality (VR), and guided audiovisual (AV) relaxation in addition to standard pharmacological management. (ConditionalVery Low)

Remarks:

  • This recommendation is based on direct evidence from patients with SCD and indirect evidence largely from postoperative adult mixed surgical populations.

  • Despite the evidence being primarily based on adult populations, there is low risk of harm in children. However, a tailored approach should be used that matches feasibility and acceptability for a given patient. Some interventions may not apply to younger children; therefore, the age of the patient should be considered, especially for interventions such as yoga and guided AV relaxation.

  • Time requirements, financial costs, availability, and training of therapists for these types of treatments are important factors in treatment selection and should be discussed with patients in the course of shared decision making.

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For adults and children who seek treatment of acute pain, the ASH guideline panel chooses not to offer a recommendation for or against acupuncture or biofeedback for the treatment of acute pain in addition to standard pharmacological management. (, )

Remarks:

  • If biofeedback and acupuncture are considered, a tailored approach is necessary that matches feasibility, acceptability, and patient experience and preference regarding these interventions for a given patient.

  • Discussion with patients in the course of shared decision making needs to include important factors such as the time, financial costs, availability, and training of the therapists required to perform these treatments.

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Pain management in an SCD-specific hospital-based acute care facility

For adults and children who develop acute pain episodes requiring hospital care, the ASH guideline panel suggests using SCD-specific hospital-based acute care facilities (ie, day hospitals and infusion centers, all with appropriate expertise to evaluate, diagnose, and treat pain and other SCD complications) over typical ED-based care. (ConditionalLow)

Remarks:

  • This recommendation assumes that these hospital-based facilities have readily available code team coverage to ensure delivery of the safest care.

  • From a hospital or system perspective, more detailed cost analyses would be warranted before deciding on implementation for a given institution. SCD-specific hospital-based acute care facilities tend to be cost effective to the extent that they reduce ED visits and admissions; however, overall acute care utilization may increase.

  • Most of the evidence describing hospital-based acute care facilities places pain treatment in the context of complex SCD comprehensive care models. In these models, >1 intervention is likely driving the improvement and continuity in care.

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Continuous basal opioid infusion for acute SCD pain treatment

For children and adults with SCD who seek treatment of acute pain in the hospital, the ASH guideline panel chooses not to offer a recommendation for or against basal opioid dosing in conjunction with on-demand dosing or scheduled intermittent dosing. (, )

Remarks: For clarity, the panel defined the specific terms used as follows:

  • Basal: continuous IV opioid infusion.

  • On-demand dosing: opioid administered at an interval that relies on patients declaring their own need. Opioid can be administered via a patient-controlled IV analgesia pump or via an as-needed order for intermittent nurse-administered drug.

  • Scheduled intermittent dosing: opioid administered on a timed schedule that does not rely on the patient asking for the drug.

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Nonopioid pharmacological therapies for chronic pain in SCD with another identifiable cause

For adults with SCD who have chronic (as opposed to episodic) pain from the SCD-related identifiable cause of avascular necrosis of bone, the ASH guideline panel suggests use of duloxetine (and other serotonin and norepinephrine reuptake inhibitor [SNRI] medications, because there is evidence of a class effect) as an option for management, in the context of a comprehensive disease and pain management plan. (ConditionalVery Low)
607
For adults with SCD who have chronic (as opposed to episodic) pain from the SCD-related identifiable cause of avascular necrosis of bone, the ASH guideline panel suggests the use of NSAIDs as an option for management, in the context of a comprehensive disease and pain management plan. (ConditionalVery Low)
607
For children with SCD who have chronic (as opposed to episodic) pain from the SCD-related identifiable cause of avascular necrosis of bone, the ASH guideline panel chooses not to offer a recommendation for or against the use of SNRIs and/or NSAIDs. (, )
607
For adults and children with SCD who have chronic (as opposed to episodic) pain from the SCD-related identifiable cause of leg ulcers, the ASH guideline panel chooses not to offer a recommendation for or against any specific nonopioid pharmacological management strategy. (, )

Remarks:

  • NSAIDs herein are defined broadly to include selective and nonselective COX inhibitors.

  • There was a lack of both direct and indirect evidence for all-cause avascular necrosis nonsurgical pain management. Therefore, the panel chose to use osteoarthritis as an indirect evidence source, because it is a degenerative arthropathy with a reasonable evidence base. This evidence base is restricted to adults.

  • Surgical and nonsurgical approaches to the treatment of the underlying cause of avascular necrosis were not the focus of this recommendation.

607
It is good practice to provide patient-centered education and surveillance related to NSAID toxicity, especially in patients with end-organ comorbidities, because long-term safety data are lacking for SCD, but vascular, bleeding, and renal risks may be elevated. (, )
(Good practice statement)
607
Given the prevalence of psychological comorbidities that are present in the context of pain, it is good practice to routinely screen for depression and anxiety and to perform targeted screening for other psychological comorbidities. (, )
(Good practice statement)
607

Nonopioid pharmacological therapies for chronic pain in SCD and no identifiable cause beyond SCD

For adults who have SCD-related chronic pain with no identifiable cause beyond SCD, the ASH guideline panel suggests SNRIs (eg, duloxetine and milnacipran) as options for pain management. (ConditionalVery Low)

Remarks:

  • This recommendation is based largely on indirect evidence from adult patients without SCD affected with fibromyalgia. Fibromyalgia was selected by panel consensus as the entity most closely aligned with chronic pain in SCD (with no identifiable cause beyond SCD).

  • Antidepressants may increase the risk of suicidal ideation and behavior in children and adolescents with major depression disorder and other psychiatric disorders.

  • The significant lack of pediatric data for the use of SNRIs for pain management could not support a recommendation for this age group.

607
For adults who have SCD-related chronic pain with no identifiable cause beyond SCD, the ASH guideline panel suggests tricyclic antidepressants (TCAs; eg, amitriptyline) as an option for pain management. (ConditionalVery Low)

Remarks:

  • This recommendation is based largely on indirect evidence from adult patients without SCD affected with fibromyalgia. Fibromyalgia was selected by panel consensus as the entity most closely aligned with chronic pain in SCD with no identifiable cause.

  • Antidepressants may increase the risk of suicidal ideation and behavior in children and adolescents with major depression disorder and other psychiatric disorders.

  • The significant lack of pediatric data for the use of TCAs for pain management could not support a recommendation for this age group.

  • The increased adverse effect profile for this drug includes, but is not limited to, prolonged QT, orthostasis, cognitive impairment, dry mouth, and anticholinergic effects. These adverse effects should be considered and discussed with patients.

607
For adults who have SCD-related chronic pain with no identifiable cause beyond SCD, the ASH guideline panel suggests gabapentinoids (eg, pregabalin) as options for pain management. (ConditionalVery Low)

Remarks:

  • This recommendation is based largely on indirect evidence from adult patients without SCD affected with fibromyalgia. Fibromyalgia was selected by panel consensus as the entity most closely aligned with chronic pain in SCD with no identifiable cause.

  • The significant lack of pediatric data for the use of gabapentinoids for pain management could not support a recommendation for this age group.

607
Given the prevalence of psychological comorbidities that are present in the context of pain, it is good practice to routinely screen for depression and anxiety and to perform targeted screening for other psychological comorbidities. (, )
(Good practice statement)
607

Nonpharmacological therapies for chronic pain in SCD

For adults and children with SCD who have chronic pain related to SCD, the ASH guideline panel suggests cognitive and behavioral pain management strategies in the context of a comprehensive disease and pain management plan. (ConditionalVery Low)

Remarks:

  • The cognitive or behavioral pain management strategy with the broadest evidence base is cognitive behavioral therapy (CBT). Other strategies considered by the panel with lower certainty in evidence include acceptance and commitment therapy (ACT), mindfulness-based treatments, coping skills training, and operant therapy.

  • This recommendation is based mainly on indirect evidence. The treatments that have been tested in SCD are in children with acute pain without establishing the presence of chronic pain or the intervention’s effects on chronic pain. The outcomes assessed in SCD have not typically included pain intensity. The greater body of indirect evidence was drawn from the literature in individuals with fibromyalgia and nonspecific lower back pain.

  • No standardized, manualized universally accepted version of CBT is available for SCD in either adults or children. This is a significant clinical and translational research need. Nonetheless, such strategies have shown broad applicability in pediatric and adult chronic noncancer pain.

  • Interventions based on CBT, coping skills training, and guided imagery have some evidence base for SCD, although mainly in children and for episodic pain.

  • In other conditions, these methods are believed to have low risks and are portable in that patients can use the skills learned on their own after treatment, possibly with intermittent booster sessions.

  • Time, financial costs, availability, and training of therapists (ie, in chronic pain and SCD) and patient burden can be barriers to these types of psychological treatments that are being recommended.

  • Cognitive and behavioral pain management strategies should be used in conjunction with other modalities as part of a comprehensive and multimodal pain management plan.

  • Behavioral and cognitive strategies are optimal in a setting where the patient is motivated and there is access to appropriately trained personnel.

607
For adults with SCD who have chronic pain related to SCD, the ASH guideline panel suggests other provider-delivered integrative approaches (eg, massage therapy and acupuncture) as available and as tolerated and conditional upon individual patient preference and response. These approaches should be delivered in the context of a comprehensive disease and pain management plan. (ConditionalVery Low)

Remarks:

  • Time, financial costs, availability, and training of therapists (ie, chronic pain and SCD) and patient burden can be barriers to these types of treatments.

  • There is currently a lack of evidence in children; however, some pediatric patients may be using these treatments at home.

607
For adults and children with SCD who have chronic pain related to SCD, the ASH guideline panel chooses not to offer a recommendation for or against a number of physical activities, exercise, or combined meditation/movement programs (including aerobic exercise, yoga, and Pilates) to improve pain and disability. (, )
607
Given the prevalence of psychological comorbidities that are present in the context of pain, it is good practice to routinely screen for depression and anxiety and to perform targeted screening for other psychological comorbidities. (, )
(Good practice statement)
607

Chronic opioid therapy for chronic pain in SCD

It is good practice to deliver patient-centered education regarding the potential to develop chronic pain and the nonopioid pain treatment options that are outlined above. (, )
(Good practice statement)
607
For adults and children with SCD and emerging and/or recently developed chronic pain, the ASH guideline panel suggests against the initiation of COT unless pain is refractory to multiple other treatment modalities. (ConditionalVery Low)

Remarks:

  • Optimization of SCD management is a priority.

  • In those whose pain has been refractory to multiple other interventions, COT should be considered after risk stratification using a validated tool, based on how well patients’ SCD is managed, comprehensive assessment of behavioral risks (eg, risk factors for opioid misuse), implications of tolerance on the management of acute pain episodes, and other known adverse effects of opioids. Adverse events noted in other non-SCD patient populations are dose dependent and include increased risk of poor surgical outcomes, increased risk of motor vehicle collisions, myocardial infarction, bone fracture, and mortality. Patients on doses of >120 mg of morphine milligram equivalents (MME) are at risk for hormonal alterations, which can lead to sexual dysfunction. Doses >100 mg of MME are associated with a ninefold increase in risk of overdose compared with doses <20 mg of MME in general non-SCD pain populations.

  • Failure criteria for a trial of COT should be discussed in the shared decision-making process, and alternative treatments in the case of failure and a plan for opioid cessation should be developed before initiation. Documentation of this discussion and the goals of care should be included in the medical record.

  • The lowest effective opioid dose should be prescribed.

  • Patients on COT should avoid the use of benzodiazepines, sedating medications, and alcohol.

  • Providers should be aware that patients may inadvertently end up on COT if episodic pain is frequent enough that patients are receiving frequent opioid treatment of recurrent pain. Therefore, providers should make efforts to reduce or eliminate scheduled opioid doses between acute episodic pain events, which may reduce the likelihood of unintentional COT.

607
For adults and children with chronic pain from SCD who are receiving COT, are functioning well, and have perceived benefit, the ASH guideline panel suggests shared decision making for continuation of COT. (ConditionalVery Low)

Remarks:

  • Optimization of SCD management is a priority.

  • The benefit of COT in SCD is largely unknown, and the harms are established via indirect evidence (recommendation 9a, remark 2); therefore, shared decision making is essential and may lead to continuation once risks of COT and tapering are explained.

  • Function should be assessed from the shared patient/clinician perspective. The use of standardized patient-reported outcome tools that assess patient functioning is encouraged.

  • COT is discussed as a class of drugs. Individual opioid drugs have different specific toxicity profiles and interactions with end-organ injury. Therefore, a review of the individual profile of each drug under consideration for use should be performed for a given patient.

  • The lowest effective opioid dose should be prescribed.

  • Patients on COT should avoid the use of benzodiazepines, sedating medications, and alcohol.

  • Patients on COT require careful monitoring with regard to functional status and risk assessment for the development of aberrant opioid use and medical, social, behavioral, or psychological complications as a precursor to opioid dose reduction or weaning.

  • The risk of adverse events related to COT rises as the total dose increases. Therefore, patients on high doses of opioids need close monitoring for complications and adverse effects.

607
For adults and children with chronic pain from SCD who are receiving COT, are functioning poorly, or are at high risk for aberrant opioid use or toxicity, the ASH guideline panel suggests against continuation of COT. (ConditionalVery Low)

Remarks:

  • Optimization of SCD management is a priority.

  • Collaboration with a pain specialist should be strongly considered for additional or alternative pain management strategies.

  • Weaning and/or withdrawal from COT is potentially a higher-risk entity in patients with SCD (ie, risk of triggering vasoocclusive events or other medical complications) and should be done carefully.

  • The other recommendations provided in this summary should be used for potential alternatives that could be part of a comprehensive pain management plan.

  • Patients on COT should avoid the use of benzodiazepines, sedating medications, and alcohol.

  • Acute pain events may still be treated with opioid analgesia if this serves the overall pain treatment plan, but this should be done in conjunction with the primary outpatient management team. Furthermore, nonopioid medications and integrative therapies should also be offered as outlined in prior recommendations.

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Good practice statements

  • It is good practice to implement harm reduction strategies for patients on COT, including strongly considering coprescribing naloxone, avoiding coprescribing opioids and benzodiazepines, and prescribing the lowest effective opioid dose.
  • It is good practice to consider collaboration with pain medicine specialists for the management of individuals living with SCD who have chronic pain.
  • In cases in which the clinician has valid and substantial evidence of aberrant opioid use, it is good practice to consider consulting an addiction medicine physician.
  • It is good practice to provide patient-centered education regarding the risks of COT.
  • Given the prevalence of psychological comorbidities that are present in the context of pain, it is good practice to routinely screen for depression and anxiety and to perform targeted screening for other psychological comorbidities.
(, )
607

Chronic transfusion therapy for recurrent acute pain and/or chronic pain

For adults and children with SCD and recurrent acute pain, the ASH guideline panel suggests against chronic monthly transfusion therapy as a first-line strategy to prevent or reduce recurrent acute pain episodes. (ConditionalLow)

Remarks:

  • In unique circumstances when all other measures to control recurrent pain episodes have failed (eg, hydroxyurea, other disease modifying therapies) and when shared decision making can be fully applied, a trial of monthly transfusions may be reasonable.

  • The decision should be influenced primarily by patient preference where patients appreciate the uncertainty in benefit over the burden and risks of monthly transfusion. Integration of education and informed shared decision making around initiation and/or cessation of chronic transfusion therapy is important.

  • IV access and adherence to chelation and erythrocytopheresis are also considerations that could favor monthly transfusions in the exceptional circumstances noted above.

  • The cessation of chronic transfusions can be associated with other SCD complications. Therefore, it is important to exercise caution if cessation of chronic transfusion is considered, including initiation of other disease-modifying therapies and increased surveillance.

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For adults and children with chronic pain from SCD, the ASH guideline panel chooses not to offer a recommendation either for or against chronic monthly transfusion therapy as an option for pain management. (, )
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Recommendation Grading

Disclaimer

Overview

Title

Sickle Cell Disease Management of Acute and Chronic Pain

Authoring Organization

Publication Month/Year

June 1, 2020

Last Updated Month/Year

July 10, 2023

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD.

 

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital, Outpatient

Intended Users

Physical therapist, occupational therapist, nurse, nurse practitioner, physician, physician assistant

Scope

Management

Diseases/Conditions (MeSH)

D000755 - Anemia, Sickle Cell, D059350 - Chronic Pain, D059787 - Acute Pain

Keywords

sickle cell disease, chronic pain, acute pain

Source Citation

Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F, Zempsky W, Lang E. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23;4(12):2656-2701. doi: 10.1182/bloodadvances.2020001851. PMID: 32559294; PMCID: PMC7322963.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
198
Literature Search Start Date
August 1, 2017
Literature Search End Date
January 1, 2019