Pain crisis

Here you will find a basic guideline for doctors to handle a pain crisis in sickle cell disease. A more general information brochure on sickle cell disease for patients or parents can be downloaded here:  Sickle cell info brochure for parents.

On this page the following key topics will be discussed:

  • Hydration
  • Cornerstones of therapy: Analgesics
  • Treatment of concomitant infections
  • Prevention


If possible (mild pain, bowel sounds present) orally or via gastric tube

Intravenously if severe pain, vomiting, lack of bowel sounds

How much?

  • Total fluids (oral + IV) per 24 h: 1500 2250 ml / m2 ; in case of pulmonary symptoms (tachypnoea, cough, chest pain) reduce total fluids to 1500 ml/m2 to prevent pulmonary edema and Acute chest syndrome

Which fluid?

  • 5% glucose + 50 mMol Na+ / l plus maintenance KCl
  • Check daily electrolytes, weight, input / output


Patients in pain need to be believed. They should be given analgesics appropriate to their pain.Giving opioids for severe pain does not lead to drug dependency. Drug dependency in sickle cell patients results from psychosocial or other problems. If the patient is admitted, he/she should receive enough analgesics to be comfortable if not pain free 1 hour after admission. It is of utmost importance to the patient to know his pain can be controlled in order to reduce anxiety – which by itself potentiates pain.

Rules for analgesia in pain crisis:

  1. Believe the patient
  2. Sufficently strong, sufficently dosed analgesics
  3. Analgesics given at intervals dictated by half life of drug
  4. With diminished pain reduce dosen not interval
  5. Slow reduction of morphine dose

Most pain crises go along with moderate fever and rise of CRP (interleukin I secretion in necrotic tissue). Children < 5 years old who have a temperature > 38,5°C need blood culture and antibiotics. Patients older than 5 years who do not have signs of a local infection and who do not appear ill do not need antibiotics. Analgetics to be used in pain crisis

Level A mild pain

  Maximal dose mg  Application Interval
Paracetamol> 15 mg / kg / dose po 4 – 6 h
Novaminsulfate 15 mg / kg / dose po 4 – 6 h
Ibuprofen 10 mg / kg / dose po 8 h

Level B moderate pain

  Maximal dose mg Application Interval
Tramadol 1 – 2 mg / kg / dose po 4 – 6 h

Level C severe pain

One of level A analgetics


  Maximal dose Application Interval
Morphin Initial bolus 0,05 mg / kg Repeat ( maximum twice) if no appreciable relieve after 20 ( 40) min Immediately start continuous infusion of 0,05 mg / kg / hour Or PCA (patient controlled analgesia) IV  

Patients on IV opioids need respiratory therapy every 2 hours with a spirometer ( 10 blows each time) to prevent hypoventilation

With improvement of pain reduction of morphine by 10 – 20 %. Oral medication (level A + B) if morhphine dose at 50 % initial dose. Decrease morphine dose slowly. If patient wants to leave prematurely retard drug like oxygesic or retard morphine for a few days is helpful

Therapy of concomitant infections

With every pain crisis, in particular if accompanied by fever, local signs of infection have to be looked for and treated appropriately


  • Pain crises can be kicked off by
    • exposure to cold (swimming pools!),
    • alcohol consumption,
    • dehydration. Patients need to be instructed to drink plenty of fluids, especially with high temperatures, physical exercise and during long distance (> 6 h) flights (very dry air in airplane),
    • avoid alcohol and nicotine
    • Smoking increases the number and intensity of pain crises.
  • Corticoids can cause severe pain crises (granulocytosis increases blood viscosity). They should, if at all, be given only in life threatening situations.
  • Patients with sickle cell disease SC often have relatively high hemoglobin levels (10 – 13 g/dl) which go along with an increased blood viscosity. SC Patients with Hb > 11,5 g/dl should have phlebotomy (10 – 15 ml blood drawn / kg and substituted by same amount of clear fluids IV or po) prior to a long distance flight.
  • Treatment of severe morphine resistant pain
  • Some adult sickle cell patients have neuropathic in addition to the usual nociceptive pain. Neuropathic pain responds poorly if at all to opioids. Antiepileptic drugs like carbamazepin or gabapentin or cannabis derivatives have been shown to be effective.


  • Every sickle cell patient with a temperature > 38,5°C ( taken twice within 1 hour) needs to be seen by a physician. Adults also have a high risk for sepsis. Patients who are treated with antibiotics as an outpatient need to be seen daily!
  • Patients < 5 year
    • Admission to hospital
  • Patients > 5 year:
    • Admission depends on clinical and general condition
    • If no admission necessary-> daily checks
  • Necessary exams:
    • CBC with retic count, blood and urine culture
    • Depending on clinical situation:
    • Chest X ray
    • Throat swab
    • Mycoplasma titer
    • spinal tap
    • If osteomyelitis is suspected: Local X- ray, ultrasound
    • Aspirate of subperiostal fluid or joint effusion
    • Stool culture ((salmonella?)
    • Antibiotics have to be effective against S. pneumonia, H. influenza and in osteomyelitis Salmonella (Ciprofloxacin).
    • With fever of unknown origin for all febrile children < 5 years and sick looking children > 5 years:
      • Ampicillin or cefotaxim IV
    • For osteomyelitis:
      • Ampicillin + Oxacillin / Clindamycin
      • Ciprofloxacin if salmonella osteo is suspected
    • With abdominal symptoms:
      • Ampicillin +Metronidazol
      • Warning: Sickle cell patients with salmonella sepsis have a high mortality due to frequent multi organ failure. Early partial exchange transfusion recommended!

Transfusion / Phlebotomy

Simple or top up transfusions or partial exchange transfusions in sickle cell patients are indicated in clearly defined situations: to inmprove oxygen carrying capacity in acute severe anema or to provide the patient with healthy erythrocytes in order to suppress the patient’s own erythropoiesis (see table 1)

Individuals with sickle cell disease HbSßThalassämie do not need a chronic transfusion regime as they do not have ineffective erythropoiesis like Thalassämia Major patients.

Main indications for simple or partial exchange transfusion

Kind of transfusion Necessary most of the time Necessary occasionally
Top up transfusion
  • Aplastic episode
  • Splenic sequestration
  • Acute Chest Syndrome
  • Severe symptomatic anemia
  • Liver sequestration
  • Acute bleeding (hematuria, GI tract, gyn)
Partial exchange transfusion
  • Immediately after CNS infarct
  • Severe infection
  • Early multi organ failure
  • Prior to neurosurgical / ophthalmol. surgery
  • Acute Chest Syndrome
  • Girdle Syndrome (paralyt. Ileus due to mesenteric vaso-occlusion)
  • Acute hepatopathy
Chronic transfusion program
  • Following CNS infarct
  • With pathological TCDS
  • Chronic renal, pulmonary, cardiac problems
  • Severe pain crisis, not responding to any analgesics

How to do a partial exchange transfusion:

  • 75% of the patient’s blood volume (75 ml / kg body weight x 0,75) is removed and replaced by the same amount of packed cells + 0,9% NaCl (2 parts packed cells, 1 part NS)
  • Example: to do a partial exchange on a 30 kg patient you have to remove 1700 ml of blood and replace it with 1130 ml packed cells and 570 ml of NS).
  • There is no need to use fresh frozen plasma. The exchange can be done via a central line or via 2 large peripheral veins. The procedure should not last longer than 2 ½ hours. To achieve an HbS level of < 30% it may be necessary to repeat the procedure the next day.

Modified partial exchange transfusion ( in fulminate Acute Chest Syndrome):

  • Phlebotomy of 10 – 15 ml / kg body weight, followed by transfusion


Do not raise a sickle cell patient’s hemoglobin above his / her “normal” hemoglobin of usually 6 – 8 g / dl. Vessels in sickle cell patients are very sensitive to overload. Overtransfusion and also very rapid transfusion results in a situation called Hyperviscosity Syndrome which is characterized by sudden arterial hypertension, seizures, cerebral bleeding and sometimes death.

Splenic sequestration


  • In HbSS and HbSß°Thal patients up to 6 – 8 years of age
  • In patients with compound heterozygous sickle cell disease (HbSß+Thal, HbSC, HbSLepore) into adult age
  • Often triggered by infection (Pneumococcus, viral infection)

Clinical presentation and lab findings

  • Spleen very large, often tender, abdominal pain, possibly fever
  • Hypovolemia, shock
  • Hb > 3 g / dl below patient’s usual level = major sequestration
  • Hb < 3 g /dl below patient’s usual level = minor sequestration
  • Massive reticulocytosis (unless triggered by Parvovirus B 19!)
  • Sometimes thrombocytopenia


Acute situation

  • Immediate transfusion in major sequestration; give half of calculated dose, as blood is mobilized from spleen and there is the risk of hyperviscosity syndrome; check hemoglobin when child out of shock and decide on necessitiy for further transfusion
  • Antibiotics
  • With minor sequestration watchful waiting if patient stable and adequate reticulocytosis

After acute episode:

  • Splenectomy independent of age after 1 major or more than 2 minor sequestrations
  • More than 50% of children will have a second episode of splenic sequestration shortly after the first episode.


In order to detect splenic sequestration as early as possible parents of infants and small children with sickle cell disease are taught to palpate the spleen with every diaper change and later whenever the child complains of abdominal pain, looks pale and sick. The parents are instructed to take the child to the hospital if a mass is felt below the left rib cage.

Acute Chest Syndrome (ACS)


  • In 40 – 50% fat embolism from bone marrow during or after pain crisis
  • Infection (mostly viral)
  • Following surgery if hypoventilation occurs
  • Hypoventilation during poorly monitored (no spirometry!) IV opioid analgesia
  • Pulmonary edema from overhydration

All of these factors can cause a dilatation of pulmonary vessels and entrapment of blood. In classical ACS there is a drop in Hb and platelets.


  • Any age

Clinic and diagnosis

  • Often during or after pain crisis
  • Chest pain
  • Fever, tachypnea, tachycardia
  • Cough is a late sign
  • Chest X ray: consolidation basal lung fields, often bilateral, with or without pleural effusion
  • Clinical signs precede Chest X ray findings!


  • Oxymetry, give O2 if indicated
  • Careful hydration, not to exceed 1500 ml / m2
  • Analgesia if indicated
  • Antibiotics
  • Bronchodilators if indicated
  • Transfusion if Hb < 6 g/dl, modified partial exchange if Hb > 6 g / dl

If clinical situation worsens or PO2 < 80mmHg: partial exchange transfusion; if acidosis and / or hypoxia despite O2 : respirator , consider NO – inhalation

ACS is no indication for anticoagulation

Translated from German Sickle Cell Guidelines

Dr. med. Roswitha Dickerhoff