II. Epidemiology
- Affects almost all Sickle Cell Anemia patients
- May occur as early as age 6 months
III. Pathophysiology
- See Sickle Cell Anemia
- Deoxygenated Hemoglobin polymerizes in triple helix chains
- Results in Red Blood Cells assuming sickled shape
- Results in Occlusion of small vessels and capillaries with secondary small tissue ischemia and infarctions
- Repeat pain crises to the same region is a risk for avascular necrosis
- Bone Marrow ischemia and hyperplasia is responsible for long bone and spine pain
IV. Risk Factors: Precipitating Triggers
- Most episodes of Vaso-Occlusive Pain Crisis are spontaneous without identified trigger
- Preceded by infection 25% of the time
- Human Parvovirus B19 is a common viral cause
- Weather changes
- Cold Weather due to reflex vasospasm
- Dehydration in warm weather
- Physical exertion
- Menstruation
- Hypoxia
- Anxiety or depression
V. Findings
- Recurrent painful crises
- Typically occurs in children under age 18 years
- Often follows a distribution pattern specific to the patient
- Sudden onset deep ache pain in Abdomen, chest, back and extremities (esp. joints)
- Episodes typically last 4 to 6 days (but may persist weeks in some cases)
- Dactylitis (infants)
- Preverbal Children presentations may be more subtle
- General
- VOC may occur as early as age 6 months
- Hemoglobin F (Hb F, fetal Hemoglobin) is protective against sickling
- Hemoglobin F wanes at age 6 months
- Inconsolable Crying
- Irritability
- Altered sleep
- Poor feeding
- General
VI. Labs
- No lab abnormality defines VOC (clinical diagnosis)
- Profound Anemia
- Reticulocyte Count <1%
- Consider additional labs in case of suspected infection
VII. Differential Diagnosis
- VOC-related Chest Pain, Abdominal Pain or back pain may present in similar fashion to other serious conditions
- Bone Pain
- Avascular Necrosis
- Avascular Necrosis of the Femoral Head
- Avascular Necrosis of the Humeral Head
- Osteomyelitis
- Infection of infarcted bone, especially long bones
- Salmonella is most common organism in Sickle Cell Anemia (S. Aureus represents <25% of cases)
- Avascular Necrosis
VIII. Precautions
- Sickle Cell Crisis is NOT typically a drug seeking mission
- Patients who present with symptoms of Sickle Cell Crisis typically have crisis
- Emergency departments see only 10-20% of Pain Crisis when severe
- Less severe episodes are treated with home management
- Vital Signs (Heart Rate, Blood Pressure) and labs do not differentiate a Sickle Cell Crisis
- Chronic severe pain leads to blunted physiologic response
- Believe patients presenting with Sickle Cell Anemia and effectively treat their pain
- Rarely, patients without Sickle Cell Anemia present with factitous crisis
- However these patients may be identified from the medical record
- Review with prescribing providers and consider behavioral health referral
- Address Drug Seeking Behavior after the acute pain crisis (treat pain adequately during crisis)
- Consider VOC therapy plan (on file in ED or patient carries with them)
- Evaluate for other concurrent sickle cell complications (esp. if pain pattern is not typical for specific patient)
IX. Management: Pain control for acute crisis
- Requires aggressive Opioid analgesia
- Avoid delays in management
- Triage patient urgently to a management bed within 30-60 minutes of presentation
- Start at outset by titrating to high dose Opioids in first 10 minutes of management
- Pain management is based on patient's reported level of pain
- Higher Opioid doses are frequently required
- Many Sickle Cell Anemia patients have developed tolerance due to Chronic Opioid use
- Avoid allowing Analgesics to wear off prior to re-dosing
- Re-evaluate pain level and sedation every 15-30 minutes
- Increase dose by 25% if inadequate pain control
- Monitor closely for respiratory depression
- Consider Patient Controlled Analgesia (PCA Pump)
- Morphine
- Initial: 0.1 to 0.15 mg/kg/dose IV (up to 10-15 mg in wt>50 kg)
- Re-evaluate and repeat as needed every 20-30 minutes initially
- Consider hospital admission for more than 2 doses required in 1-2 hours
- Later
- ORAL: 0.15 to 0.3 mg/kg/dose (up to 10 to 20 mg in wt>50 kg) PO every 3 to 4 hours OR
- IV: 0.05 to 0.1 mg/kg/dose (up to 2 to 5 mg in wt>50kg) IV every 2 to 4 hours
- Initial: 0.1 to 0.15 mg/kg/dose IV (up to 10-15 mg in wt>50 kg)
- Hydromorphone (Dilaudid)
- Initial: 0.01 mg/kg up to 1 mg IM or IV
- Adults may require 1 to 4 mg per hour
- Later
- ORAL: 0.03 to 0.08 mg/kg/dose (up to 1 to 4 mg in wt>50kg) PO every 3 to 4 hours OR
- IV: 0.015 mg/kg/dose (up to 0.2 to 0.6 mg) IV every 3 to 6 hours
- Initial: 0.01 mg/kg up to 1 mg IM or IV
- Fentanyl Intranasal
- Dose: 1-2 mcg/kg up to 100 mcg/dose every 15 minutes for up to 2 doses
- Consider if IV Access is delayed
- Avoid delays in management
-
Non-Opioid Analgesics
-
Acetaminophen
- Adjuct in mild to moderate pain
-
NSAIDS
- High Incidence of occult renal dysfunction in Sickle Cell Anemia (Exercise caution)
- Serum Creatinine typically underestimates renal dysfunction in Sickle Cell Anemia
- NSAIDS may be used for mild to moderate pain, or adjunctive relief if no contraindications
-
Acetaminophen
- Avoid agents with adverse effects
- Avoid Meperidine (Demerol)
- Meperidine metabolite normeperidine is neurotoxic and associated with increased Seizure risk
- Meperidine is associated with euphoria and less effective Analgesic effect
- Morphine or Dilaudid are preferred over Meperidine (Demerol)
- Avoid parenteral Antihistamines
- Avoid Meperidine (Demerol)
- Avoid agents not shown to offer benefit
- Blood Transfusions are not indicated for routine management of vaso-occlusive crisis
- However, Blood Transfusion is indicated in specific circumstances
- Hemoglobin <6 g/dl or significant drop from baseline (e.g. >2 g/dl)
- Consider in severe Tachycardia or Hypotension
- However, Blood Transfusion is indicated in specific circumstances
- Magnesium does not appear to reduce pain, reduce Opioid use or reduce lengths of ED stays
- Antiplatelet agents (e.g. Prasugrel) does not appear to prevent vaso-occlusive crisis
- Blood Transfusions are not indicated for routine management of vaso-occlusive crisis
X. Management: Other Measures
-
Intravenous Fluids
- Avoid Fluid Overload (risk of Atelectasis and Acute Chest Syndrome)
- Limit total fluid to <1.5x maintenance requirements
- On achieving euvolemia, consider maintenance with Hypotonic Saline (D5 1/2NS) which may enter the RBC
- Oxygen
- Only indicated in Hypoxia (Oxygen Saturation <93%) or in cardiopulmonary compromise
- Oxygen may be associated with a higher risk of Bone Marrow suppression and secondary need for Blood Transfusions
- Incentive Spirometry
- Decreases Atelectasis risk and risk of Acute Chest Syndrome
- Adjunctive measures
- Local heat (warm compresses) applied to painful area
XI. Management: Disposition
- Admission criteria after 3 Opioid doses is likely to be too restrictive and result in over-admitting
- Consider longer emergency department course (up to 6 hours) for pain stabilization to determine if admission indicated
- Hospitalization Indications
- Complicated presentations
- Acute infections not meeting discharge indications below
- Serious complications (e.g. Acute Chest Syndrome, Sepsis, sequestration crisis, Osteomyelitis)
- Abnormal Vital Signs
- Pregnancy
- Lack of reliable outpatient follow-up
- Opioid diversion
- Observation Unit Indications
- Hospitalization indications NOT met
- Uncomplicated VOC with failed home and 6 hour emergency department stay
- Anticipated discharge within 48 hours
- Discharge indications when acute infection complicates Vaso-Occlusive Pain Crisis
- Nontoxic appearance
- Patient able to take oral fluids and medications
- Able to maintain therapy compliance
- Close medical follow-up is available
- Close follow-up is needed in all patients after Vaso-Occlusive Pain Crisis (VOC)
- Increased risk of associated complications (e.g. Acute Chest Syndrome)
XII. Course
- Acute Crisis usually resolves spontaneously 7-10 days
XIII. References
- Claudius, Behar and Sadowitz in Herbert (2018) EM:Rap 18(4): 10-2
- Dwyer, Kleinmann, Goswami and Lopez (2025) Crit Dec Emerg Med 39(1): 26-35
- Glassberg and Weingart in Herbert (2012) EM: Rap 12(8): 5-6
- Lopez, Kleinmann, Chandra and Lopez (2025) Crit Dec Emerg Med 30(3): 4-12
- Lowe and Wang (2018) Crit Dec Emerg Med 32(11): 17-25
- Welsh and Welsh (2016) Crit Dec Emerg Med 30(11): 15-23
- Preboth (2000) Am Fam Physician 61 [PubMed]
- Yawn (2015) Am Fam Physician 92(12): 1069-76 [PubMed]