Treatment

True of false: an acute painful sickle cell episode should be treated as a medical emergency?

True

Yes, because of the intense pain and because it may progress to acute chest syndrome if not promptly and aggressively managed.

False

Supportive care includes which of the following?

Supplemental oxygen even if oxygen saturation > 95%

Administer oxygen if patient has oxygen saturation < 95% on room air.

Use of incentive spirometry while awake

Yes, to reduce the risk of acute chest syndrome.

Hydration

Correct. Oral fluids if patient able to tolerate, otherwise intravenous. Avoid overhydration by checking daily intake/output, daily weight, and presence of edema.

Red cell transfusion if Hb < 8.5 g/dL

There is no magical hemoglobin (Hb) trigger for transfusion in this setting. It depends on the presence of symptoms and the degree of change in Hb from baseline.

Pain control

YES! Initiate analgesic therapy within 30 minutes of triage, or within 60 minutes of registration. There is no standard protocol available, but there should be a low threshold for using opioids.

Options for pain management include:

NSAIDS

Consider short course (5-7 days) of NSAIDs in addition to opioids. If serum creatinine is above the upper limit of normal for age, consider holding NSAIDs, especially in the presence of albuminuria.

Opioids

Mainstay of treatment.

Local heat application

Adjunct therapy.

Ketamine

Adjunct therapy.

Corticosteroids

Use of corticosteroids for acute pain management suggested against.

Pain management in vaso-occlusive crisis

Currently, opioids constitute the mainstay of treatment for acute pain when patients with sickle cell disease (SCD) seek care in a health care setting.

Other options for pain control in SCD include:

Acetaminophen
Anesthetics
Sodium channel blockers
Gabapentinoids (Neurontin and Gabapentin)
Tramadol
Tapentadol
Cannabinoids
Ketamine
Venom-derived compounds (Ziconotide)

Clinical practice guideline recommendations for treating pain in vaso-occlusive crisis

2014 NHLBI guideline:

Evidence from several randomized control trials and observational studies support the use of opioid therapy in treating vaso-occlusive crises (VOCs).

2020 guideline recommendations from the American Society of Hematology:

For adults and children with sickle cell disease (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).
For adults and children with SCD presenting to an acute care setting with acute pain related to SCD for whom opioid therapy is indicated, the ASH guideline panel suggests tailored opioid dosing based on consideration of baseline opioid therapy and prior effective therapy (for adults: conditional recommendation based on moderate certainty in the evidence about effects).
For adults and children with acute pain related to SCD, the ASH guideline panel suggests a short course (5 to 7 days) of nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to opioids for acute pain management (conditional recommendation based on very low certainty in the evidence about effects).
For adults and children presenting for acute pain related to SCD, the ASH guideline panel suggests against corticosteroids for acute pain management (conditional recommendation based on low certainty in the evidence about effects).
For adults and children presenting with acute pain related to SCD who are hospitalized, the ASH guideline panel suggests a subanesthetic (analgesic) ketamine infusion as adjunctive treatment of pain that is refractory or not effectively treated with opioids alone (conditional recommendation based on very low certainty in the evidence about effects.
For adults and children presenting with acute pain related to SCD, the ASH guideline panel suggests regional anesthesia treatment approaches for localized pain that is refractory or not effectively treated with opioids alone (conditional recommendation based on very low certainty in the evidence about effects.
For adults and children who seek treatment of acute pain, the ASH guideline panel suggests massage, yoga, transcutaneous electrical nerve stimulation (TENS), virtual reality (VR), and guided audiovisual (AV) relaxation in addition to standard pharmacological management (conditional recommendation based on very low certainty in the evidence about effects.

A reminder of the patient’s complete blood counts:

Date	WBC (10⁹/L)	Hb (g/dL)	MCV (fL)	PLT (10⁹/L)
Day of admission	11.2	6.3	105	403
2 months earlier	7.3	7.9	106	313

Assuming that the patient is asymptomatic from her anemia, should she be transfused?

Yes

The drop in Hb is typical for a patient with vaso-occlusive crisis. See explanation for not transfusing her on the next slide.

Clinical practice guideline recommendations for transfusion in vaso-occlusive crisis

NHLBI recommendations:

Acute anemia, defined as a decline by 2.0 g/dL or more in hemoglobin concentration below the patient’s
baseline value

British Society of Hematology recommendations:

Bottom line:

Bottom line: do not routinely transfuse your patient with vaso-occlusive crisis… only if there is another indication to do so!

The patient has an oxygen saturation of 96% on room air. Should she be provided with supplemental oxygen?

Yes

You ignore the recommendation not to administer supplemental oxygen, and provide the patient with 2 liters oxygen by nasal prongs. You end up obtaining an arterial blood gas on her and show that the PO₂ is 168 mmHg. That’s a big jump from a normal arterial PO₂ of 90-100 mmHg. Does it represent a significant improvement in her blood oxygen content and oxygen delivery?

Yes

Correct. See next slide for an explanation.

Oxygen delivery = cardiac output x oxygen content of blood

Oxygen content of blood = (Hb x SaO2 x oxygen binding capacity of Hb) + amount of dissolved oxygen in blood

Oxygen binding capacity of Hb = 1.39 ml oxygen/gram Hb
Dissolved oxygen in blood 0.003 ml oxygen x PaO2

Oxygen delivery = cardiac output x ([Hb x SaO2 x 1.39] + [0.003 x PaO2])

On room air:

Oxygen delivery = cardiac output x ([Hb x 96 x 1.39] + [0.003 x 100])

On 2L nasal prongs:

Oxygen delivery = cardiac output x ([Hb x 100 x 1.39] + [0.003 x 168])

As you can see from the above calculations, the change in oxygen content and oxygen delivery is minimal when the patient is provided with supplemental oxygen!

Course in hospital

The patient was treated with opioids. Her oxygen saturations were consistently > 95%, so she did not require supplemental oxygen. She was instructed to use incentive spirometry every 4 hours while awake. She was initially started on IV fluids (normal saline) because she was in too much pain to take liquids orally, but she was transitioned to oral fluids shortly thereafter. She was not transfused with red cells. Her pain subsided over the next 5 days, and her hemoglobin increased to her baseline of about 8 g/dL. She was discharged from the hospital feeling fatigued, but otherwise well.

Schematic of what the patient received and did not receive:

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