Because direct evidence was primarily from small RCTs, and because there was a high degree of heterogeneity in the included indirect evidence that was reviewed, the recommendation was downgraded to conditional based on the certainty in the evidence that was identified. Searches for direct evidence were completed in August 2017. Without specific evidence to judge, the panel agreed that potential benefits of IV fluids could include improved pain intensity, shorter length of stay, decreased hospitalization and ED rates, and decreased opioid use. Data reviewed included both pediatric and adult populations to inform this question and recommendation. Technological innovations, such as the use of mobile applications, may improve accessibility, but such interventions are in early stages of development. There is no one-size-fits-all approach to optimal pain management. Documentation of this discussion and the goals of care should be included in the medical record. However, the panel did not limit questions based on potential availability of data. The panel acknowledges that opioid delivery via PCA offers clear advantages over alternative drug delivery strategies. Although the panel expected that desirable effects overall might be small, the panel also concluded that undesirable effects were smaller, and the benefits outweighed them. Therefore, all data reviewed were from published systematic reviews and meta-analyses conducted in another chronic noncancer pain population, those with fibromyalgia. These plans can be embedded in the electronic medical record and used to guide opioid dosing. Patients on doses of >120 mg MME are at risk for hormonal alterations, which can lead to sexual dysfunction. The potential benefits of regional anesthesia use in the treatment of acute pain in SCD are small and include improved pain control, reduced opioid utilization, and improved patient satisfaction. In 2016, ASH initiated an effort to develop clinical practice guidelines on Sickle Cell Disease (SCD). For researchers: the recommendation is supported by credible research or other convincing judgments that make additional research unlikely to alter the direction of the recommendation. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain Author links open overlay panel Amanda M. Brandow 1 … The independent impact of the site of care separate from other aspects of the care delivery model is difficult to assess. These studies did not report on outcomes of pain coping, HRQOL, or return to baseline pain. Furthermore, nonopioid medications and integrative therapies should also be offered as outlined in prior recommendations. Because chronic pain is now recognized as a distinct entity in patients with SCD, the ASH guideline panel had the opportunity to do a more in-depth evaluation of the available evidence for chronic pain management. Implementation of the guidelines will be facilitated by forthcoming decision aids. The acute painful crisis is the most common acute complication of sickle cell disease (SCD). The guideline panel determined that there is overall very low certainty in the evidence for a net benefit of massage, yoga, TENS, VR, and guided AV relaxation to reduce the burden and psychosocial impact of acute pain in patients with SCD. However, these are typically active strategies, which require significant time and effort on the part of the patient. High-dose opioids for chronic non-cancer pain: an overview of Cochrane reviews, Opioids for chronic noncancer pain: a systematic review and meta-analysis, The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop, Long-term opioid management for chronic noncancer pain, Opioids for chronic non-cancer pain in children and adolescents, Opioid tolerance—a predictor of increased length of stay and higher readmission rates, Opioid dose and risk of road trauma in Canada: a population-based study, Opioid use for noncancer pain and risk of myocardial infarction amongst adults, Opioid use for noncancer pain and risk of fracture in adults: a nested case-control study using the general practice research database, Prescription opioids for back pain and use of medications for erectile dysfunction, Opioid prescriptions for chronic pain and overdose: a cohort study, Opioid dose and drug-related mortality in patients with nonmalignant pain, The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription, The opioid drug epidemic and sickle cell disease: guilt by association, Cohort study of the impact of high-dose opioid analgesics on overdose mortality [published correction appears in, Guidance on opioid tapering in the context of chronic pain: evidence, practical advice and frequently asked questions, Patient-centered prescription opioid tapering in community outpatients with chronic pain, Prescription opioid taper support for outpatients with chronic pain: a randomized controlled trial, Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice, Opioid cessation and multidimensional outcomes after interdisciplinary chronic pain treatment, Development and validation of shortened, restructured Treatment Outcomes in Pain Survey instrument (the S-TOPS) for assessment of individual pain patients’ health-related quality of life, Development and validation of an eight-item brief form of the SOAPP-R (SOAPP-8), Development of a brief version of the Current Opioid Misuse Measure (COMM): the COMM-9, Efficacy of the opioid compliance checklist to monitor chronic pain patients receiving opioid therapy in primary care, Risk factor assessment for problematic use of opioids for chronic pain, Prescription opioid abuse in chronic pain: an updated review of opioid abuse predictors and strategies to curb opioid abuse (part 2), Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia, Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease, A phase 3 trial of l-glutamine in sickle cell disease, Crizanlizumab for the prevention of pain crises in sickle cell disease, National Heart, Lung, and Blood Institute Expert Panel. An iterative process was conducted to reach consensus about pain populations that were most closely related to SCD patients with chronic pain without an identifiable cause beyond SCD. 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. In other diseases, clinical pathways are thought to be cost effective. Enjoying our content? Therefore, few participants had frequent recurrent pain or chronic pain at the time of study entry. Therefore, the panel agreed to search the indirect evidence for chronic noncancer pain populations other than SCD. There is currently a lack of evidence in children; however, some pediatric patients may be using these treatments at home. The data on cost effectiveness were too limited to develop conclusions. In children and adults who seek treatment of acute pain, should a standardized protocol be used that includes (1) reduced time to first dose (<1 h from arrival) in addition to more frequent reassessment and dosing of pain medication (<30 min) and (2) tailored dosing (vs weight-based dosing)? Of these studies, there were 4 RCTs, 1 case series, and 1 safety study. 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 (strong recommendation based on low certainty in the evidence about effects ⨁⨁◯◯). However, this report did not address the use of red blood cell transfusion for recurrent acute pain or chronic pain in children or adults with SCD.185  Therefore, the panel sought to systematically review the existing data and appraise the evidence to determine whether monthly transfusion should be used to prevent or reduce recurrent acute pain or chronic pain in this population. The panel’s recommendations are divided into 3 defined medication groups and are based on the clear presence of chronic (rather than episodic) pain. The panel based these recommendations on the following definitions for COT: (1) patients receiving a ≥70-day supply of opioids in a 90-day period153  or (2) an index opioid prescription in the past 4 months followed by at least 2 more opioid prescriptions and having at least a 60-day supply of opioids within the 4-month period. Chronic SCD pain without contributory disease complications: chronic pain is more likely due to central or peripheral nervous system sensitization and has a nonidentifiable cause. 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, the panel carefully defined a non-ED treatment center as an SCD-specific hospital-based acute care facility (ie, day hospital, infusions center). In the U.K., guidelines are provided by the National Health Services (NHS) and the National Institute for Health and Care Excellence (NICE). The majority of patients would want the recommended course of action, but many would not. The panel did raise a few concerns about how SCD-specific hospital-based acute care facility models could reduce health equity. Schlaeger et al118  conducted a small pilot RCT comparing pregabalin with placebo; however, the trial had a large dropout rate, resulting in findings that do not guide treatment options. The potential risks associated with regional anesthetic use in SCD patients, as in other populations, include hypotension, motor blockade, fever, infection, and urinary retention. Fibromyalgia was selected by panel consensus as the entity most closely aligned with chronic pain in SCD with no identifiable cause. 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 included the geographical location of these facilities and the fact that ED access may be easier in some circumstances if patients arrive via emergency medical services. Overall, the panel concluded that the patient resources needed, including financial costs, time, and effort, were likely to be moderate, although there was little evidence to support this conclusion. 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. Should a combination of continuous basal opioid infusion with on-demand dosing vs on-demand opioid dosing alone or scheduled intermittent opioid dosing be used for children and adults with SCD hospitalized for the treatment of acute pain? Patient preferences should drive clinical decisions. Should nonopioid pharmacological therapies either in addition to or instead of opioids or other usual care interventions be used for the treatment of acute pain in children and adults with SCD? American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain The panel acknowledges that this definition may not encompass all acute pain that is experienced by individuals, because acute pain is often managed at home. The hope is that these guidelines will provide structure around the management of acute and chronic SCD pain and identify areas of research needed that incorporate important patient-centered outcomes with the ultimate goal of decreasing pain-related suffering for individuals living with SCD. They may also be used by patients. The panel determined that engaging patients in a discussion about chronic nonopioid therapy proactively during their baseline state of health is warranted. In response to these issues, ASH addressed these concerns via a meeting and letter to the CDC asking for clarification of these guidelines.197  In response, the CDC recently released a written clarification of these guidelines stating that the recommendations were not intended to apply to patients with SCD.197  Recommendation 9 expands on the NHLBI guidelines and puts forth a patient-centered individualized approach for the use of COT in patients with SCD that balances benefits and harms for a given patient. The included studies contain reports of nystagmus, visual hallucinations, dizziness, and dysphoria in patients with SCD who received ketamine. Therefore, the panel concluded that the benefits of chronic nonopioid therapy for individuals living with SCD and suffering from chronic pain are limited to adult populations and include the medications pregabalin, duloxetine, milnacipran, and amitriptyline, based on indirect evidence. 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. However, they may also have significant risks, especially in this chronically ill population. The panel sought to identify the most relevant painful complications of SCD that were independently associated with chronic pain and to systematically review the existing data and appraise the evidence to determine if it was sufficient to recommend any nonopioid pharmacological strategies to treat the pain associated with these conditions and, if so, which could be recommended. The position of the panel was that it would be inappropriate to weigh in on the use of cannabis, a drug that is illegal in the United States of America at the federal level. Celecoxib demonstrated a statistically significant reduction in total WOMAC score (MD ,  −4.41; 95% CI, −7.27 to −1.55), the WOMAC pain scale (MD, −0.86; 95% CI, −1.10 to −0.62), and the WOMAC function subscale (MD, −2.90; 95% CI, −5.12 to −0.67). The panel discussed the known risks of chronic nonopioid therapy that have been published in the indirect literature regarding adult patients in the chronic noncancer pain population of fibromyalgia patients. Furthermore, there is a need for research into system barriers and solutions to these barriers to provide the evidence base that can facilitate successful implementation of this recommendation. The indirect evidence reviews focused only on published systematic reviews and meta-analyses that addressed the use of chronic nonopioid therapy for fibromyalgia in pediatric and adult populations. Therefore, the panel also sought to evaluate the evidence for the efficacy and/or effectiveness of chronic transfusion therapy as a treatment of recurrent acute and chronic pain. In part A of the forms, individuals disclosed direct financial interests for 2 years before appointment; in part B, indirect financial interests; and in part C, not mainly financial interests. Transportation to and from an SCD-specific hospital-based acute care facility may be more difficult for patients without access to private vehicles. Equity was also felt to be potentially increased with the SCD-specific hospital-based acute care facility model, because there may be prompter return to work after treatment as a result of more rapid treatment. There was also very limited direct evidence in individuals living with SCD upon which to base these recommendations. One study of methotrexate for crisis pain reported reductions in chronic avascular necrosis pain as a secondary outcome, but this outcome was inadequately described, and the study was not designed to address chronic pain.95  Another small study investigated sodium salicylate iontophoresis as an add-on to conventional physical therapy and medications and was limited by small sample size, rigor of methods, and limited descriptions of the control vs intervention groups.96  The 1 study identified as possible direct evidence for leg ulcers was a case series reporting outcomes of subcutaneous calcium heparin plus human antithrombin concentrate in adults with sickle cell β thalassemia, which addressed wound healing rather than pain.97. Evidence for or against 4 therapeutic options was identified by the systematic review of evidence: NSAIDs, corticosteroids, subanesthetic ketamine, and regional anesthesia. 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. Q10. The panel agreed that the guidelines needed to address both acute and chronic pain. The study of pain is challenging, and the gold standard of pain assessment is self-report. The same review156  also sought to compare the effectiveness of opioids and nonopioid pharmacological pain therapies (eg, NSAIDs, TCAs, and anticonvulsants), with a focus on the outcomes of pain relief and functioning. In addition to conducting systematic reviews of intervention effects, the researchers searched for evidence related to baseline risks, values, preferences, and costs and summarized findings within the EtD frameworks.10,11,16  Subsequently, the certainty in the body of evidence (also known as quality of the evidence or confidence in the estimated effects) was assessed for each effect estimate of the outcomes of interest following the GRADE approach based on the following domains: risk of bias, imprecision, inconsistency, indirectness, risk of publication bias, presence of large effects, dose-response relationship, and an assessment of the effect of residual, opposing confounding. In addition to synthesizing evidence systematically, the Mayo Center supported the guideline development process, including determining methods, preparing meeting materials, and participating in panel discussions of evidence. Sickle pain experience is influenced by psychological response to pain… The panel discussed the idea that the cost effectiveness may be hard to fully understand, because the savings from reduced hospitalizations may be offset by increased acute care utilization in the SCD-specific hospital-based acute care facility because of more rapid treatment and reduced stigma. This study was unable to assess for an impact on utilization or patient-reported outcomes; however, it did demonstrate the challenges with implementation of efforts to facilitate faster analgesia in the ED. Also, the panel agreed that significant time, personnel commitment, and moderately high costs are required to deliver these therapies. The variability in study outcomes used made it difficult to pool data across studies. As discussed above, an iterative process was used to reach panel consensus on the questions where indirect evidence was relevant and on which pain populations this evidence would be drawn from. These approaches should be delivered in the context of a comprehensive disease and pain management plan (conditional recommendation based on very low certainty in the evidence about effects ⨁◯◯◯). Other limitations included the small sample size, nonuniform opioid dosing, and specific opioid administered across studies. The studies were conflicting and heterogeneous, with small sample sizes; therefore, the recommendation is conditional based on low to moderate certainty in the evidence about effects. Furthermore, the need for repeated epidural catheter insertion for recurrent painful events may raise concerns regarding feasibility. 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. COT is discussed as a class of drugs. There was minimal direct evidence identified that informed this question in patients with SCD. The complete EtD framework for this question, including evidence tables, is provided as an online supplement: https://guidelines.gradepro.org/profile/b955e360a93d1c73908ba3f4548bc944. You’ve viewed {{metering-count}} of {{metering-total}} articles this month. Other purposes are to inform policy, education, and advocacy and to state future research needs. Formal decision aids may be beneficial for clinicians to help individual patients make decisions. Despite the absence of direct evidence for acute recurrent pain, this conclusion is reasonable given the high prevalence of potential harms from monthly blood transfusions and the absence of high-quality data showing effect. The panel identified few undesirable effects of movement-based therapies; however, exercise tolerance, exertion sensitivity, hydration, and anemia may limit acceptability and feasibility for individuals living with SCD. Additionally, families and caregivers should be advised to closely observe the patient and to communicate with the treating clinician. It is desirable to have coping strategies, and generally, the panel believed that patients would be willing to dedicate time to learn skills such as CBT. Given the high prevalence and impact of chronic pain, investigations that address how chronic transfusion therapy affects chronic pain should be prioritized. The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell … Table 3 provide GRADE’s interpretation of strong and conditional recommendations by patients, clinicians, health care policymakers, and researchers. Good practice statement It is good practice to provide patient-centered education regarding the risks of chronic opioid therapy. There were no studies that addressed some of the a priori–defined patient-centered outcomes, including pain, HRQOL, satisfaction with care, and missed days of school or work. Conflicts of interest of all participants were managed through disclosure, panel composition, and recusal, according to ASH policies based on recommendations of the Institute of Medicine20  and the GIN.9  Participants disclosed all financial and nonfinancial interests relevant to the guideline topic. Members of the ASH Guideline Oversight Subcommittee reviewed the guidelines in relation to this late disclosure and agreed that the conflict was unlikely to have influenced any of the recommendations. Because there were only 4 RCTs, the recommendation was downgraded to conditional based on certainty of the evidence ranging from low to intermediate. Therefore, many institutions have developed alternative models of care for acute pain that include delivery of pain management in a treatment center outside of the ED such as in a day hospital, observation unit, or infusion center. The absence of data specifically for individuals with SCD should also be discussed. Recently, there has been a greater understanding of the complex nature of pain in SCD such that better definitions of acute pain, chronic pain, and acute-on-chronic pain have emerged.18,40  Most studies in this review predated these definitions. This underscores the need for pediatric-specific investigations focused on the impact of therapies for acute and chronic SCD pain. The systematic review identified 1 RCT (36 participants, 56 pain episodes) from the direct evidence that addressed the use of corticosteroids in children and adolescents (age <21 years) with SCD hospitalized for acute pain treatment.47  Evidence for the following outcomes existed in this RCT: (1) length of stay: there was a decrease in length of stay in conjunction with opioids and (2) opioid utilization: the study failed to demonstrate reduced opioid utilization. The studies were mostly retrospective and heterogeneous and had low sample sizes. However, the assessment of savings will depend on the volume of patients in the center. This should include a discussion of the risks of COT and of the insufficient evidence that addresses the benefits of COT. The greater body of indirect evidence was drawn from the literature in individuals with fibromyalgia and nonspecific lower back pain. 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. The majority of the direct evidence that was available included small numbers of participants and was noncomparative with a significant lack of phase 3 RCTs. The authors concluded from this study that their results could not be used to determine overall safety of a continuous opioid infusion. For clarity, the panel defined the specific terms used as follows: Children and adults living with SCD require hospitalization for acute pain management. The review team then searched for systematic reviews of pain interventions in these populations. Despite the widespread use of COT for chronic pain, there is variability in practice, likely driven by the paucity of data to support or refute its use. In addition to efficacy, this research should particularly focus on risks and adverse events in patients with SCD. There was 1 small-scale RCT of massage in adults (mean age, 32.8 years),138  1 observational study of acupuncture in adults (age range, 19-67 years),66  2 single-arm pilot studies of biofeedback in children (age range, 7-17 years),132  and 1 in children and young adults (age range, 10-20 years).139  Evidence for the following outcomes existed, all with very low certainty in the evidence about effects: (1) pain intensity,138  (2) functioning,132  (3) HRQOL,132  (4) anxiety,139  (5) intensity and frequency of pain episodes,139  (6) number of days analgesics were used,139  and (7) global impression of treatment effectiveness,139  rated as fair to very effective. The panel felt that patients and caregivers place a high value on treatments for acute pain that have the potential to be effective and opioid sparing. The systematic review did not identify any direct evidence in individuals living with SCD that informed this question. The panel acknowledges that there was no important uncertainty or variability about how much people value the main outcomes that were considered. The panel noted that some interventions may not be feasible for all age groups, especially very young children. The outcomes assessed in SCD have not typically included pain intensity. Importantly, no studies that were included in the systematic reviews and meta-analyses followed patients beyond 6 months. 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. 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