AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks public-private partnership with the U.S. Food and Drug Administration and the American Pain Society, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative developed the outline of an optimal diagnostic system for chronic pain conditions. Subsequently, a working group of experts in SCD pain was convened to generate core diagnostic criteria for chronic pain associated with SCD. The working group synthesized available literature to provide evidence for the dimensions of this disease-specific pain taxonomy. A single pain condition labeled chronic SCD pain was derived with 3 modifiers reflecting different clinical features. Future systematic research is needed to evaluate the feasibility, validity, and reliability of these criteria.

Review/overview of pain in sickle cell disease

Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids.     

AAAPT Diagnostic Criteria for Acute Sickle Cell Disease Pain

Acute pain episodes are the most common complication in patients with sickle cell disease (SCD). Classically attributed to vaso-occlusion, recent insights suggest that chronic pain may also contribute to the pathogenesis of acute pain episodes, which adds complexity to their diagnosis and management. A taxonomy, or classification system, for acute pain in patients with SCD would aid research efforts and enhance clinical care. To meet this need, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public–private partnership with the U.S. Food and Drug Administration, the American Pain Society, and the American Academy of Pain Medicine formed the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks–American Pain Society–American Academy of Pain Medicine Pain Taxonomy initiative. One of the goals of this initiative was to develop taxonomies for acute pain disorders, including SCD. To accomplish this, a working group of experts in SCD and pain was convened. Based on available literature and expert opinion, the working group used a 5-dimenional structure (diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms) to develop an acute pain taxonomy that is specific to SCD. As part of this, a set of 4 diagnostic criteria, with 2 modifiers to account for the influence of chronic pain, are proposed to define the types of acute pain observed in patients with SCD.PerspectiveThis article presents a taxonomy for acute pain in patients with SCD. This taxonomy could help to standardize definitions of acute pain in clinical studies of patients with SCD.     

Pain Management Issues as Part of the Comprehensive Care of Patients with Sickle Cell Disease

BackgroundVaso-occlusive pain crisis is one of the primary complications of sickle cell disease (SCD) and is responsible for the majority of hospital visits in patients with SCD. Stints of severe pain can last for hours to days and are difficult to treat and manage, often resulting in drastically reduced quality of life.PurposeOur purpose is to provide an overview of pain management issues in SCD populations.MethodsWe explored literature using PubMed and Embase for the etiology and management of pain in SCD. Databases were searched employing the following terms: sickle cell, pain pathways, pain perception, pharmacological therapies, psychological therapies, physical therapies and genetics.ResultsPain in SCD can vary from acute to chronic (persistent) or mixed and understanding of the underlying mechanisms is important for proper pain management. Currently, there are many means of managing pain in children with SCD, which involve pharmacological and non-pharmacological approaches. A combination of psychotherapy and pain medications can be used for treatment of pain and other psychosocial co-morbidities in complex persistent pain.ConclusionsProviding more appropriate medication and optimal dosage based on individual's genomic variations is the future of medicine, and this will allow the physicians to hone in on optimal pain management in patients with SCD.     

Psychological Characteristics and Pain Frequency Are Associated With Experimental Pain Sensitivity in Pediatric Patients With Sickle Cell Disease

Sickle cell disease (SCD) is associated with episodes of severe vaso-occlusive pain beginning in infancy with a subset of patients with SCD transitioning to chronic pain. Response to experimental pain using quantitative sensory testing in these patients suggests altered pain processing. The objectives of this study were to characterize sensitivity to multiple modalities of experimental pain stimuli and to interrogate the relationship of psychological covariates, clinical pain burden, and pain-related outcomes to experimental pain sensitivity in children with SCD compared with healthy individuals of similar age and sex. Cross-sectional assessments of psychological characteristics were performed, and quantitative sensory testing methods were used to measure experimental pain sensitivity in children age 8 to 21 years. Anxiety, depressive symptoms, catastrophizing, and somatization were found to be associated with increased sensitivity to experimental pain stimuli. Increased frequency of painful episodes in SCD was associated with decreased sensitivity to heat pain and decreased mechanical temporal summation. These data suggest that careful consideration be given to psychological factors, age, sex, and clinical burden of pain when studying response to experimental pain in SCD.

Integrative approaches to treating pain in sickle cell disease: Pre-clinical and clinical evidence

Sickle cell disease (SCD) is a genetic disorder characterized by hemolysis, end-organ damage, inflammation, and pain. Recurrent and unpredictable episodes of acute pain due to vaso-occlusive crises are a unique feature of SCD. Many patients also develop lifelong chronic pain. Opioids are the primary method of pain treatment in SCD; however, continued use is associated with several adverse effects. Integrative approaches to treating pain in SCD are increasingly being explored to prevent the side effects associated with opioids. In this review, we highlight the mechanisms of pain in SCD and describe mechanism-based integrative approaches for treating pain.     

Use of red blood cell exchange for treating acute complications of sickle cell disease

Sickle cell disease (SCD) is a life-threatening chronic condition primarily caused by genetic mutation. The disease is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Acute complications in patients with SCD are difficult to manage due to the pathophysiological nature of the disease. Transfusion therapy is the cornerstone of management of acute complications and significantly reduces SCD morbidity and mortality. Red cell exchange (RCE), which is characterized by low iron accumulation and volume overload, has been widely used for transfusion therapy in recent years.     

A Healthcare Improvement Initiative to Increase Multidisciplinary Pain Management Referrals for Youth with Sickle Cell Disease

BackgroundChronic pain is a complex integration of biological, psychological, and social variables. Multidisciplinary pain management experts design interventions that treat the multidimensional experience. Children and adolescents with sickle cell disease (SCD) are at risk for chronic pain. Increased risk is associated with multiple characteristics including sickle cell genotype, age, gender, frequency of hospitalization, duration of hospitalization, and certain comorbid diagnoses. Referral to pain management professionals for this population is often delayed.AimsTo increase multidisciplinary pain management referrals for youth with SCD identified to be at risk for chronic pain.DesignImplementation research.SettingOne pediatric, academic medical facility serving as a regional sickle cell treatment center in the Midwest.ParticipantsChildren greater than 2 years of age and less than 21 years of age with laboratory confirmed SCD.MethodsImplementation of an evidence-based screening tool using the consolidated framework for implementation research (CFIR) to guide project planning, design, and evaluation. The CFIR model was paired with the Plan-Do-Study-Act (PDSA) quality improvement methodology to operationalize workflow and sustain project aims.Results and ConclusionsEighty-four percent of all eligible patients were screened during their routine sickle cell appointments resulting in a 110% increase in multidisciplinary pain management referrals. Future interventions and PDSA cycles are targeted at improving attendance at scheduled appointments, reducing hospitalizations, decreasing 30-day readmissions, and shortening length of stay.     

Managing the acutely ill adult with sickle cell disease

Sickle cell disease (SCD) is an autosomal recessively inherited condition, affecting the structure of the haemoglobin. SCD is a long-term chronic condition which is manifested by periods of acute painful sickling crisis, known as vaso-occlusive crisis (VOC) and is the cause of 90% of sickle cell-related hospital admissions. SCD is one of the most common genetic conditions worldwide and in the UK there are approximately 12,500 people living with it (Streetly et al,1997; Howard et al, 2008), making it more common than cystic fibrosis, yet there still remains many challenges in managing these patients when they become acutely ill. Lack of awareness and understanding of the illness, concerns regarding addiction and limited attention to the psycho-social implications of the illness, leads to less than effective care for this patient group when they are hospitalized. The aims of this article are to outline the pathophysiology of SCD, identify the causes of VOC and discuss the key principles of nursing management for patients experiencing a VOC.     

Evaluation and Management of Sickle Cell Disease in the Emergency Department (An 18-year Experience): 1974--1992

Painful episodes are the most frequent complaints of patients with sickle cell disease. The Emergency Department (ED) has provided management for acute events using the usual triage format for emergencies. A prospective study evaluated the role of the ED in the care of adults with sickle cell disease (SCD). The protocol, thus, addressed issues of acute events related to SCD and provided better care for patients with SCD in the ED. Approximately 37% of ED visits were for painful events. An inciting cause was identified in 35% of painful events and 75% of these required admission to the hospital. A 15-year follow-up prospectively showed similar results and that uncomplicated pain crisis can be treated with ED protocols. Outpatient clinics and urgent centers could reduce these visits. Absolute indications for admission include sepsis, fever >102 degreeF, white cell counts >20 000, worsening anemia, hypoxemia, acute chest syndrome and new CNS events. Patient database in the ED must be revised annually to avoid extensive workup in the ED and a complete history/physical examination, and a CBC could be sufficient for triage in an uncomplicated pain crisis. An acceptable protocol for care should be available at all EDs and a registry and information system for SCD will discourage overutilization of investigational tests and visits to multiple EDs.     

A primary care provider's guide to preventive and acute care management of adults and children with sickle cell disease

Purpose: To familiarize primary care providers (PCPs) with the pathophysiological processes, diagnostic evaluation, and medical management of sickle hemoglobinopathies and their complications. Current standards of care, clinical research advances, and new treatment options will also be addressed to assist PCPs in the management of sickle cell disease (SCD).
Data sources: A selective search and review of the current literature on SCD and the authors' experience.
Conclusions: Management of individuals with SCD is very complex, requiring a multidisciplinary approach that includes the patient or parent, PCP, specialist, nurse, and social worker. More patients living with SCD are relying on PCPs in nonspecialty practices for comprehensive disease management.
Implications for practice: Newborn screening detects new cases of SCD annually. The median life expectancy has more than doubled for individuals with sickle cell anemia. Healthcare providers are now in an era of increased routine screening, assessment, and management of chronic complications from this illness not previously seen in the care of adults with SCD.     

Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis

Sickle Cell Disease (SCD) is a chronic hemolytic disorder associated with frequent pain episodes, end organ damage and a shortened lifespan. Currently there exist no disease specific targeted therapies for the treatment of acute vaso-occlusive crisis (VOC) and management with analgesics and hydration is purely supportive. Improvement in understanding of disease pathophysiology has resulted in a great interest in disease modifying novel therapies and many are being evaluated in clinical trials. Here we report the results from the pre-specified mid-point analysis of the Phase 2 study of Intravenous Gamma Globulin (IVIG) for the treatment of acute VOC in patients with SCD and lessons learned.     

CRISPR/Cas9 gene editing for curing sickle cell disease

Sickle cell disease (SCD) is the most common monogenic blood disorder marked by severe pain, end-organ damage, and early mortality. Treatment options for SCD remain very limited. There are only four FDA approved drugs to reduce acute complications. The only curative therapy for SCD is hematopoietic stem cell transplantation, typically from a matched, related donor. Ex vivo engineering of autologous hematopoietic stem and progenitor cells followed by transplantation of genetically modified cells potentially provides a permanent cure applicable to all patients regardless of the availability of suitable donors and graft-vs-host disease. In this review, we focus on the use of CRISPR/Cas9 gene-editing for curing SCD, including the curative correction of SCD mutation in β-globin (HBB) and the induction of fetal hemoglobin to reverse sickling. We summarize the major achievements and challenges, aiming to provide a clearer perspective on the potential of gene-editing based approaches in curing SCD.     

Sickle cell disease: health promotion and maintenance and the role of primary care nurse practitioners

PURPOSE: To discuss the role of nurse practitioners (NPs) with regard to early identification of affected individuals, effective monitoring and screening, effective pain management and prophylaxis, and health education for patients with sickle cell disease (SCD). DATA SOURCES: Electronic database searches were performed using Medline, Cinahl, and PsycINFO. Data were obtained from medical textbooks, research, and review articles. CONCLUSIONS: SCD is a chronic inherited disease belonging to a group of conditions called hemoglobinopathies. Individuals with SCD often require close medical care from specialists. Nonetheless, NPs are in ideal positions to facilitate the health promotion and health maintenance necessary to decrease the high rate of morbidity and mortality associated with this disease. IMPLICATIONS FOR PRACTICE: NPs must understand the importance of early identification of affected individuals, effective monitoring and screening, effective monitoring and screening, effective pain treatment, and prophylaxis. The unpredictable trajectory of SCD can lead to frustration, fear, helplessness, hopelessness, and emotional distress. Ineffective pain management is a major problem for people with SCD. NPs can overcome this problem by initiating effective and prompt pain management in a nonjudgmental manner.     

Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso‐Occlusive Episodes in Adolescents with Sickle‐Cell Disease

Patients with sickle‐cell disease (SCD) can experience recurrent vaso‐occlusive episodes (VOEs), which are associated with severe pain. While opioids are the mainstay of analgesic therapy, in some patients with SCD, increasing opioid use is associated with continued and increasing pain. Dexmedetomidine, an α₂‐adrenoreceptor agonist with sedative and analgesic properties, has been increasingly used in the perioperative and intensive care settings and has been shown to reduce opioid requirement and to facilitate opioid weaning. Therefore, there might be a role for dexmedetomidine in pain management during VOEs in patients with SCD. Here, we present the hospital course of 3 patients who during the course of VOEs had severe pain unresponsive to opioids and ketamine and were treated with dexmedetomidine. Dexmedetomidine infusions that lasted for 3 to 6 days were associated with marked reduction in daily oral morphine‐equivalent intake and decreases in pain scores (numeric rating scale). There were no hemodynamic changes that required treatment with vasoactive or anticholinergic agents. These preliminary findings of possible beneficial effects of dexmedetomidine in decreasing opioid requirements support the hypothesis that dexmedetomidine may have a role as a possible analgesic adjuvant to mitigate VOE‐associated pain in patients with SCD.     

Acceptability and Feasibility of a Mindfulness-Based Intervention for Pain Catastrophizing among Persons with Sickle Cell Disease

BackgroundFew investigators have developed and tested nonpharmacological interventions for helping persons with sickle cell disease (SCD) manage persistent pain.AimsThe purpose of this pilot study was to examine the feasibility and acceptability of a mindfulness-based intervention (MBI) in adults with SCD and chronic pain and to gather preliminary data on its efficacy.DesignData on feasibility and acceptability, including recruitment, retention, and attendance rates, were collected during a single-site, randomized control trial. Participants were randomly assigned to either a 6-session group telephonic MBI or a wait-listed control. Pain catastrophizing was assessed at baseline and at weeks 1, 3, and 6.SettingOutpatient, comprehensive, interdisciplinary sickle cell disease center in the Southeast.Participants/SubjectsAdults at least 18 years of age with a self-reported diagnosis of sickle cell disease who self-identified as having chronic, non-cancer pain that persisted on most days for at least 6 months and adversely affected function and/or well-being.MethodsSeventy-eight adults were recruited; 18 (23%) declined to participate; 60 were randomly assigned to either the MBI (N = 40) or control (N = 20). Of those, 14 (35%) from the MBI and 12 (60%) from the control group withdrew immediately after random allocation, resulting in 34 evaluable cases (MBI: N = 26; control: N = 8).ResultsAmong the 26 assigned to MBI, the median number of sessions attended per person was 4; 7 (27%) attended all six sessions. Qualitative findings indicated that MBI participants viewed the program as acceptable and liked the telephonic format, community, and content. Reductions in pain catastrophizing outcomes were identified after intervention.ConclusionsAn MBI is feasible and acceptable for persons with SCD experiencing chronic pain. A larger randomized controlled trial to establish MBI efficacy on pain and related outcomes for SCD will provide nonpharmacologic, behavioral pain management options for nurses and other clinicians caring for persons with SCD and chronic pain.     

Acute thoracic aortic dissection: The basics

With an increasing incidence, aortic dissection is the most common acute illness of the aorta. In the setting of chronic hypertension, with or without other risk factors for aortic dissection, this diagnosis should be considered a diagnostic possibility in patients presenting to the emergency department with acute chest or back pain. Left untreated, about 75% of patients with dissections involving the ascending aorta die within 2 weeks of an acute episode. But with successful initial therapy, the 5-year survival rate increases to 75%. Hence, timely recognition of this disease entity coupled with urgent and appropriate management is the key to a successful outcome in a majority of the patients. This article reviews acute thoracic aortic dissection, including ED diagnosis and management.     

Do Children with Sickle Cell Disease Receive Disparate Care for Pain in the Emergency Department?

Background: There may be disparities in pain management practice in the emergency department (ED) for sickle cell disease patients (SCD) with vaso-occlusive episodes (VOE). Objectives: To compare pain management practice for children who presented to the ED with VOE to those with isolated long bone fractures (LBF). Methods: Children who presented with a VOE or a LBF to a children's hospital ED during 2005 were included. A retrospective medical chart review was conducted for each patient visit. Data collected included demographics, pain scores, time from triage to analgesia, and analgesic intervention. Results: Seventy-seven patients with SCD had 152 visits to the ED for pain, and 219 patients had 221 visits for LBF. Fifty-five patients (108 visits) with SCD and 123 patients (124 visits) with LBF received opiates. Subsequent analysis was done on these groups. Patients with SCD were older, less likely to be male and more likely to be African-American than the LBF group. Patients with SCD had higher triage pain scores (7.7 ± 2.5 vs. 6.7 ± 3.0, p = 0.005) and spent less time in the waiting room (7.4 ± 9.0 vs. 12.1 ± 26.8 min, p = 0.10), were given higher initial opiate doses (0.09 ± 0.03 vs. 0.07 ± 0.03 mg/kg morphine, p < 0.001); however, time from triage to analgesic intervention did not differ (69.0 ± 42.6 vs. 70.4 ± 57.1 min, p = 0.92). Conclusions: No disparities in care for children with sickle cell pain were identified. More timely administration of opiates needs to be encouraged, assuming other factors such as time of day, ED census, and acuity permit.