Sickle cell disease (SCD) patients are at increased risk for a whole slew of life-threatening problems. One of the many reasons they are vulnerable is because people with SCD are functionally asplenic, so they’re more likely to suffer from serious bacterial infections like meningitis, osteomyelitis, and septic arthritis. For a variety of reasons, they’re also more likely than the general population to suffer from cholecystitis, priapism, leg ulcers, avascular necrosis of the hip, acute coronary syndromes, pulmonary embolism, and even sudden exertional death. Many of these diagnoses present with pain similar to a sickle cell crisis and can be challenging because the presentations of some are less typical than usual.

Sickle Cell Pain Crisis Is a Diagnosis of Exclusion

Patients with SCD can sometimes present a challenge when it comes to pain management because it’s often difficult to discern whether they’re malingering. The majority of SCD patients suffer real pain but may not look uncomfortable because they have learned to adapt to a lifetime of chronic pain. In the emergency department, they may appear calm, be preoccupied with their handheld device, or be casually chatting. The rates of true opioid addiction in sickle cell patients are low (less than 5 percent), and the literature suggests that emergency physicians undertreat pain in sickle cell patients. I recommend that unless there is clear evidence the patient does not have SCD, take the patient’s complaint seriously and use analgesics aggressively in the emergency department.

As in all of emergency medicine, physicians need to think of the worst diagnoses first. Therefore, it is imperative not to assume that a patient with SCD who is in pain is suffering from a sickle cell crisis. If the pain is different from previous pain crises, broaden your differential diagnosis to include not only all the painful conditions that should be considered in all emergency patients but also sickle cell–specific conditions such as acute chest syndrome. The diagnosis of a pain crisis is a clinical one; no laboratory test will reliably determine whether the patient is suffering from a pain crisis, and SCD has been described in all races. Do not assume that a patient does not have SCD just because they have a light skin color. Sickle cell patients presenting with an uncomplicated pain crisis will often have normal vital signs. Any abnormal vital signs (especially fever) should raise the suspicion of alternative diagnoses. Examine joints and soft tissues looking for evidence of cellulitis, septic joints, osteomyelitis, and joint avascular necrosis. Perform a careful respiratory exam looking for evidence of an acute chest syndrome. Look for hepatosplenomegaly if you have a concern for splenic sequestration.

Lab tests are not routinely required for SCD patients presenting to the emergency department with a pain crisis. A complete blood count, reticulocyte count, liver function tests, bilirubin, lactate dehydrogenase, and electrolytes should be considered if you suspect another diagnosis, the patient is systemically unwell, or you suspect worsening anemia or jaundice. In SCD patients with fever, have a very low threshold to do a septic workup and start empiric antibiotics. An important pitfall in the diagnosis of a pain crisis is assuming that a normal serum hemoglobin rules it out. Patients with a higher baseline serum hemoglobin level are more likely to suffer pain episodes due to vaso-occlusion. Consider admission for febrile patients without an identified source. The reticulocyte count is of particular value in sickle cell patients who present with a sudden drop in their serum hemoglobin level in order to distinguish a sequestration crisis from an aplastic crisis.

Pain Management in the ED

Emergency physicians often underdose analgesics in SCD patients. A general rule of thumb for initial dosing of opioids is to administer the patient’s usual total daily dose in a single IV dose. Frequent reassessments with self-reported pain should guide repeat doses. Consider hydromorphone or morphine every 15 to 30 minutes until pain is under control, and escalate the dose by 25 percent for uncontrolled pain. Consider adjunctive medications including acetaminophen, NSAIDs, and ketamine. Note that while NSAIDs have been shown to be effective in managing sickle cell pain crises, they should be avoided for long-term treatment of pain in SCD patients because of the potential renal side effects as these patients are at increased risk for chronic renal failure. Case reports support the effectiveness of ketamine as an opioid-sparing drug. While corticosteroids have been shown to reduce pain scores and length of stay, they are associated with high rates of pain recurrence, and so I do not recommend them.

Oxygen and Fluids: Do Not Give Routinely

Reserve supplemental oxygen for patients who are hypoxic. Oxygen has never been shown to improve outcomes in SCD patients suffering from a pain crisis. Supplemental oxygen is thought to suppress bone marrow and increase transfusion requirements. If the oxygen saturation is greater than 92 percent, no supplemental oxygen is needed.

Reserve fluid boluses for patients who are hypovolemic. While it is thought that dehydration may precipitate a pain crisis, overhydration does not help resolve a pain crisis and may have detrimental effects such as atelectasis, which may precipitate acute chest syndrome and hyperchloremic metabolic acidosis, promoting sickling. Resuscitate hypovolemic patients only to euvolemia, and for maintenance fluids, use a hypotonic solution such as half normal saline (½ NS) or dextrose 5%–half normal saline (D5-½ NS).

Is There a Role for Red Blood Cell Transfusions?

There is no role for red cell transfusions in an uncomplicated acute pain crisis. Transfusions can lead to an increased risk of alloimmunization and may increase pain by increasing viscosity of blood leading to vaso-occlusion as well as precipitate acute chest syndrome and stroke.

Acute Chest Syndrome

Acute chest syndrome is the most common cause of death in SCD. Like all classic triads in medicine, the classic triad of acute chest syndrome (fever, hypoxia, and pulmonary infiltrate) is often not present. Acute chest syndrome can present fairly benignly with a bronchitis-like or pneumonia-like clinical picture with cough and shortness of breath, but patients often do not develop a fever. The pain of acute chest syndrome is characterized by a T-shirt distribution. A sickle cell patient with isolated chest pain without any other symptoms can be safely presumed to be suffering from a sickle pain crisis, whereas any associated respiratory symptoms should raise the possibility of acute chest syndrome. Any degree of hypoxia, even if the chest X-ray is initially normal, should be considered to be acute chest syndrome until proven otherwise. The sooner patients with acute chest syndrome are diagnosed, the sooner they can receive lifesaving treatment with a simple red blood cell transfusion or exchange transfusion in consultation with a hematologist. In addition to usual resuscitative measures, broad-spectrum antibiotics should be initiated.

Thanks to Dr. Richard Ward and Dr. John Foote, the guest experts on the EM Cases podcast that inspired this article.

Dr. Helman is an emergency physician at North York General Hospital in Toronto. He is an assistant professor at the University of Toronto, Division of Emergency Medicine, and the education innovation lead at the Schwartz/Reisman Emergency Medicine Institute. He is the founder and host of Emergency Medicine Cases podcast and website.