A Holistic, Tailored Approach to Pain Management in SCD Improves Patient Trust

In sickle cell disease (SCD), inherited mutations in hemoglobin cause red blood cells to become rigid and sickle-shaped, obstructing microvascular flow and triggering inflammation, hemolysis, and vaso-occlusion. For hospitalists, one of the most urgent consequences is severe acute pain that requires rapid, individualized, and bias-aware treatment.

When these sickle-shaped cells obstruct microvascular flow, this leads to episodes of intense pain, termed vaso-occlusive episodes or pain episodes (formerly termed “pain crises”), which sometimes require treatment in a hospital. Yet for a variety of reasons, including bias and structural racism, clinicians sometimes underestimate pain in people with SCD, and these individuals have not always had their pain needs adequately met during a vaso-occlusive episode.

Dr. Huss

For hospitalists, the practical priorities are straightforward but often difficult to execute consistently: believe patient-reported pain; treat within the first hour; use individualized pain plans whenever available; reassess frequently; balance adequate analgesia with oversedation risk; and communicate clearly at discharge to preserve continuity.

“Trust the patient and the pain level that they are reporting to you,” emphasized Blaine Huss, MD, MHA, a hospitalist with Yale New Haven Hospital, in New Haven, Conn., which has a dedicated inpatient SCD unit. “Please take their pain seriously.”

Dr. Fatima

“Many patients with sickle cell disease who are hospitalized for acute pain episodes feel that their concerns and experiences could be better heard and acknowledged,” said Shaheen Fatima, MD, a hospitalist affiliated with Emory University School of Medicine and Grady Memorial Hospital in Atlanta. “Assessment and management of pain shouldn’t just be about medications. It should employ a whole-person, holistic approach.”

Understanding Sickle Cell Disease

Proper management of SCD requires an understanding of the full scope of the disease and its impact on patients. Previously, SCD largely led to childhood mortality. Due to newer treatment and monitoring practices, most children in resource-rich countries now live to adulthood, although with a life expectancy currently three decades shorter than the general population.¹

However, with these improvements, some of the long-term complications of SCD from progressive organ damage have become more evident. For example, patients may suffer from chronic kidney disease, liver disease, neurological impairments from silent infarcts or stroke, or pulmonary hypertension related to acute chest syndrome, all of which hospitalists must assess and consider. Patients can differ significantly in these manifestations, or in their baseline levels of hemoglobin.¹

“There is such a range in how sickle cell patients present,” Dr Huss said. “It’s really important that we get to know them and see them as individuals.”

Avascular necrosis is another important complication. These and other skeletal abnormalities from recurrent vaso-occlusive episodes can lead to chronic pain syndromes that are sometimes difficult to treat, even when patients are not in the midst of a pain crisis. Some patients have sources of pain with clear origins on imaging, such as avascular necrosis, but a subset of other patients develop pain of more nociplastic origin.

Current guidelines from the American Society of Hematology (ASH) emphasize a holistic, multimodal approach for chronic pain in SDC, including options such as serotonin and norepinephrine reuptake inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or nonpharmacological approaches such as cognitive behavioral therapy and massage therapy for appropriate patients. However, some patients still require chronic opioids from their outpatient practitioners to manage their refractory chronic pain.²

Treatment Landscape

Disease-directed options remain limited. Three medications to date have been approved by the U.S. Food and Drug Administration (FDA) to treat SCD long-term: hydroxyurea, l-glutamine, and crizanlizumab. The latter, although still currently available in the U.S., has been removed from European markets following some contradictory phase 3 results, which are being pursued in a follow-up trial.¹

A fourth medication, voxelotor, was approved in 2019, but the manufacturer abruptly removed it from the market in 2024 over safety concerns. Despite research efforts, no treatments have yet been approved by the FDA to shorten the duration or intensity of sickle cell pain episodes, leaving practitioners with no disease-specific treatments and only symptomatic approaches to address pain.¹

Some of this reflects challenges of sickle cell research itself and consequent multiple disappointing results from phase 3 trials. However, historically, sickle cell disease has also been comparatively underfunded in research from government and private foundations, with fewer specialized centers compared to a genetic condition like cystic fibrosis, which affects primarily white patients; ASH and advocacy groups are making serious efforts to address these research disparities to achieve better treatments.^3,4

Although hematopoietic stem cell transplants and now newer FDA-approved gene therapies provide exciting opportunities for potential disease cure in select individuals, many practical barriers to implementation exist; most patients will still require pharmacologic care with occasional treatment for vaso-occlusive episodes.   

Practitioner Biases Toward SCD Patients

Vaso-occlusive pain episodes are the most common reason for hospitalization in people with SCD. Hospitalizations have decreased for individuals with sickle cell disease over the past 15 years, partly due to greater reliance on specialized outpatient settings that can often deliver treatment more quickly compared to general emergency rooms. However, such centers are not available everywhere, and some patients still require treatment in a hospital setting to achieve adequate pain control or to treat complications from a pain episode.⁵

Unfortunately, some patients still experience stigma and implicit or explicit bias, especially from physicians with less experience with this population. Race, socioeconomic status, and bias against patients who need opioid treatment can all play a role.⁶ Some clinicians may misattribute a patient’s legitimate attempts to seek treatment for their pain crisis as drug-seeking behavior. Experiences of stigma can worsen the mental and emotional impact of the disease for patients, contributing to greater perceived pain and worse quality of life for patients.³

Dr. Patidar

“Provider attitude and behavior towards patients in a pain crisis varies,” Dr. Fatima said. “There are often opportunities to further strengthen patient-centered care.” She pointed to the importance of avoiding assumptions about drug-seeking behavior, as opioid use disorder among patients with SCD occurs at rates similar to the general population.⁷

Compared to other patients needing opioid treatment, such as those with renal colic, patients with SCD experiencing a vaso-occlusive pain episode may be treated less quickly in a general emergency department, even when patients are in comparable amounts of pain.⁸

Although some rare, outlier, high-utilizer patients exhibiting higher risk behaviors do exist, these are definitely not typical sickle cell patients, explained Viniya Patidar, MD, another hospitalist with Emory Healthcare.

Dr. Readlynn

Jennifer Readlynn, MD, SFHM, a hospitalist with the University of Rochester Medicine in Rochester, N.Y., shared that her center has made multiple efforts on both the inpatient and outpatient level to improve practitioner continuity for patients and also address psychosocial elements. Such efforts, she believes, have made such patients even less common.

Dr. Press

Valerie Press, MD, MPH, SFHM, is a hospitalist researcher and a professor of medicine and pediatrics at the University of Chicago. She urges clinicians to be compassionate and nonjudgmental towards the small proportion of patients with SCD who do have some degree of opioid use disorder.

“It’s just another condition you treat, like high blood pressure,” Dr. Press said. “It shouldn’t mean not treating their pain from a vaso-occlusive episode or judging them for having a dependency inflicted on them by a very painful disease.”

Treat Within the First Hour

Diagnosis of an SCD episode is a clinical one, with no straightforward markers to distinguish it from other potential pain sources which can also affect SCD patients, noted Dr. Patidar. It’s important, Dr. Fatima added, to ask patients about whether the pain they are experiencing resembles the pain that they’ve had from previous vaso-occlusive episodes. Chart review and discussing the medical history are key to knowing about patients’ previous experiences of pain episodes and complications like acute chest syndrome.

Dr. Fatima pointed out that an inherent challenge is that pain is a multifaceted and subjective experience. Social and psychological factors help mediate the pain experience, and this experience of pain can differ significantly among individuals. This can make it more difficult to validate objectively compared to conditions with more straightforward markers, and in some cases this can contribute to under-recognition and undertreatment.

Dr. Press added that pain from a vaso-occlusive episode may look very different from pain caused by another event, such as a car accident, leading unfamiliar practitioners to underestimate it.

“Many individuals with sickle cell disease often sit very still, trying to distract themselves, such as by watching a movie,” Dr. Press said. Dr. Huss agreed that pain during an SCD pain episode is sometimes greater than the physical exam findings might indicate.

It’s critical for physicians to repeatedly and consistently demonstrate to patients that they take their pain seriously. Dr. Readlynn shared that this approach improves patient trust over time.

“I’m a white woman, and our patients with sickle cell disease are mostly Black, and understandably they have hesitancy in trusting providers a lot of the time,” she said. “To build that relationship, we need them to know that we believe their pain.”

Pain episodes should be treated quickly and adequately, with frequent titrations of both the dose and frequency of delivery. Patients should receive treatment within the first hour of emergency department (ED) arrival, or ideally within the first 30 minutes, with reassessment and possible additional doses of opiates every 30 to 60 minutes. These episodes cause excruciating pain, notes Dr. Press, so it’s important to get patients quick relief.

“Triaging and getting pain under control quickly is going to decrease how long they’re in a pain episode,” added Dr. Readlynn. “When patients are stressed from pain, that contributes to the inflammation and the sickling.” She shared that her center has changed its triaging priorities, so that sickle cell patients are now treated more quickly in the ED. Such quick treatment may help reduce the number of patients who eventually need hospital admission while also helping to reduce the risks of complications.⁹

Managing SCD Pain as a Hospitalist

Hospitalists must manage all aspects of a hospitalized SCD patient’s care during their hospital course, including monitoring and treating pain episodes as well as potential complications and comorbid conditions.

Practitioners treating pain episodes should follow recommendations from the latest ASH guidelines, but these carry significant room for interpretation, and the guideline on pain management has not been updated since 2020.² For any complex cases, it’s often essential to enlist the help of a consulting team, especially for more critical patients who may need blood transfusions, exchange transfusions, or adjunctive pain modalities.

Use Individualized Pain Plans When Available

A key element of this care is managing the pain itself. This can require rather large doses of opiate drugs, with even higher doses in patients on chronic outpatient opiate treatment or patients frequently hospitalized for pain crises. Dosing must be tailored to the patient’s baseline opioid therapy and previously effective regimens rather than a generic weight-based dosing protocol.

“It is challenging to take care of sickle cell patients with a high pain requirement,” said Dr. Patidar. “That’s why it’s ideal to have a multidisciplinary approach to figure out how to best care for them and take out that variability from provider to provider.”

Dr. Huss shared that many trainees or physicians who are not experienced with sickle cell disease can be very uncomfortable prescribing opiates at these higher levels. “Do not be afraid of using higher doses in this population, whose pain is very severe,” Dr. Huss urged, “but continue to watch for physical signs of oversedation.”

Tailor Opioid Therapy and PCA Use

Patient-controlled analgesia (PCA) devices, recommended as part of ASH guidelines, can deliver a specified dose of opiates (at no more often than a programmed interval).² Dr. Press noted that IV opiates often wear off quickly and can’t always be administered as frequently as needed; PCAs are often an ideal approach, and they give patients more autonomy and control. PCAs also give helpful information about a patient’s pain status via how often the patient activates the device. PCA’s are typically not available in most ED settings, but they are an option at most dedicated sickle cell day programs and urgent care centers. 

Dr. Fatima noted that some physicians may not be comfortable ordering a PCA, but that readily available SCD order sets can help with confidence and willingness to do so.

“For hospital systems, I would really advocate for developing a standardized order set,” agreed Dr. Patidar. She believes that such order sets can increase consistency across physicians in terms of pain treatment and other evidence-based aspects of care of SCD, like incentive spirometry to prevent acute chest syndrome, specific intravenous fluid requirements, or transfusion protocols. Dr. Huss also recommends the pharmacy team as a resource if clinicians are feeling uncomfortable with a patient’s opiate requirements.

Dr. Patidar also noted that PCA alone may not be sufficient for all patients. For example, patients on long-term long-acting opiates will continue to need their long-acting oral opiate medications in addition to treatment for the pain event itself.   

Ideally, both ED and hospitalist clinicians should be able to use electronic medical records to access patients’ individualized pain plans, as recommended by guidelines from ASH.² These include information developed with the help of their outpatient physician about how best to manage a specific patient’s acute vaso-occlusive pain event, specifying the different modalities, doses, etc.

Dr. Fatima believes that employing such individualized pain plans increases consistency among clinicians, which can help improve patient trust. However, she explained that sometimes an individualized pain plan might need to be modified (with communication with the patient and the hematology consult team), e.g., if a patient is having unexpected complications or if their pain needs still aren’t being met.

These individualized plans can reduce variability from physician to physician and reinforce the message that the clinical team understands the patient’s history, prior treatment response, and goals for care.

Hospitalists must also continue to monitor for pain during hospitalization, decreasing pain medications as the pain episode diminishes and readying patients for discharge. In addition to the direct patient report of their pain, Dr. Fatima shared that a 10-question tool, the Functional Status-based Pain Assessment, can give additional information about how well a patient’s pain is being managed, as patients rate how easily they can perform various tasks of everyday living. Although not yet fully validated, it can help give a fuller picture of the patient’s pain status.¹⁰

Balance Adequate Analgesia with Oversedation Risk

One inherent challenge of pain management in SCD is that practitioners must avoid both undertreatment of pain episodes—a significant problem—and also overtreating with opioids while neglecting to use multi-modal approaches, noted Dr. Press.

Oversedation can be a problem from overtreatment, as can the development of opioid tolerance and even opioid-induced hyperalgesia, a condition in which long-term opiate use paradoxically makes the body more sensitive to pain.

Dr. Huss noted that starting a patient on a low-normal PCA setting is usually a safe way to avoid oversedation, and true oversedation is very rare when practitioners carefully follow their institutional policies on SCD. She also recommends oral over intravenous diphenhydramine, an antihistamine drug which patients sometimes require for opioid-induced itching. Naloxone drips at very low doses can also help patients avoid oversedation from antihistamines.

Adjunctive pain methods are a key element in avoiding opiate overtreatment. Some more readily available options include NSAIDS (oral, topical, or intravenous), acetaminophen, lidocaine patches, and hot or cold packs. However, Dr. Readlynn points out that SCD comorbidities need to be considered in this approach, e.g., existing kidney or liver damage and consequent risks from NSAIDs or acetaminophen.

Dr. Press shared that she and others at the University of Chicago have also explored the utility of virtual reality tools as a nonpharmacological method to decrease pain via mental distraction, giving the brain something to focus on besides the pain experience. Dr. Press said, “Especially in pediatrics, people are thinking about judicious use of opioids and using more multimodal therapies to extend the viability of opioids, so patients can still get relief from them decades later.”

Although pharmacological management of SCD itself has not advanced much in the last several years, some important adjunctive methods for managing pain have become more commonly used. Tools such as ketamine, nerve blocks, or lidocaine drips may require more collaboration with consulting services, and they are not available at all institutions.

Dr. Readlynn shared that for patients who have more significant opiate side effects without sufficient relief, the team might consider additional pain alternatives, like ketamine. In the past, this has necessitated transfer to the ICU for intravenous ketamine, but now they sometimes use oral ketamine on the floor.

According to Dr. Huss, lidocaine and ketamine drips have provided critical tools to provide minimally sedating pain relief while sparing opioid use as much as possible. She noted that ketamine helps reset patients’ pain tolerance, and it can be a very helpful treatment for opioid-induced hyperalgesia. When ketamine first became available, her center only used it for refractory patients.

“Now we often use it earlier in patients’ treatment courses, particularly for established patients requiring higher amounts of opiates,” she said.

Intravenous lidocaine is also a helpful opiate-sparing option, especially for SCD-related bone pain. Dr. Huss and colleagues have used it without serious complication, but it should be avoided in those with neurological comorbidities. Because of its potential impact on the heart and nervous system, these patients may need to be maintained on telemetry for adequate monitoring. 

Continuity for Better Pain Management

While navigating these newer options and avoiding under- and over-treatment, a personalized approach is key. In some contexts, like for a patient new to one’s health system, it can take extra effort to get the necessary information and make a tailored plan.

Perhaps even more than in some other patient populations, continuity of care is extremely important in SCD to improve patients’ experience and increase their sense of trust. As health systems evolve to provide more targeted care, patients should ideally be seen by physicians who can get to know them over time, whether in an outpatient day program setting or on dedicated SCD floors. If that’s not possible, advises Dr. Huss, don’t hesitate to communicate with outpatient practitioners or specialized consulting teams.

Written communication by hospitalists, e.g., in the form of discharge notes or updated pain plans, is also key to ensure continuity moving forward.

Dr. Press said, “That way, the next time that individual comes in they can have more continuity, as opposed to having a different clinician with a different mindset every time.”  

Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine in Bloomington, Ind., and a freelance medical writer.

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