Sickle Cell Disease
 Management of an Adult With an Acute Pain Episode

1. After assessment of patient for cause of pain, select medication and loading dose based upon prior history and current assessment
A) usual medication, dosage, side effects
B) usual medication taken at home successfully
C) medication taken since the onset of pain
D) for opiod naïve adults weighing > 50 kg initial loading dose may be morphine 10-30 mg orally (immediate release) or 2.5-5 mg IV.

2. For severe pain, intravenous administration is the route of choice
A)  Morphine: easy to convert to oral extended or immediate release.  If this causes pruritus see below for treatment.  If significant allergy then use alternative medication.
B) Hydromorphone:  Alternative for individuals with significant morphine allergy
C)  Demerol:  Not recommended.

3. For mild to moderate pain, after initial relief obtained, consider maintenance with oral medication.  If patient presented with crisis that usual pain regimen did not resolve, consider: 1. adjuvant medications if not already being used, 2. switching medications, or 3. providing some prn breakthrough doses.

Titration approach:
1. Give loading dose; reassess in 15-30 minutes
RELIEF:  see definition below
       a) yes- maintain relief with around the clock scheduled
         doses and prn rescue dosing.
        b) no- treat with bolus, ¼- ½ of the loading dose
c) reassess and treat Q 15-30 minutes, then maintain relief with maintenance around the clock dosing with scheduled oral pain medication or provide continuous basal rate with PCA.  Medication should be administered with dosing interval that does not extend beyond duration of desired pharmacological effect.
d) provide rescue dose of approximately ¼ - ½ of one around the clock dose, set limits for number of rescue doses over a period of time.  If intravenous, provide rescue dose of ¼ - ½ of hourly opiod dose at least Q 30 minutes.  If frequent rescue doses are required,  maintenance dose is adjusted upward or the dosing interval is decreased.
e) Patient controlled analgesia is indicated if pain is inadequately controlled with bolus titration or if frequent dosing is required for relief maintenance.
f) Adjuvant therapies:  antihistamines, oral NSAIDs, acetaminophen, parenteral ketoralac.
g) side effect monitoring:  see below
h) NOTE:  Patients with PCA pumps should be instructed not to leave the nursing unit.  If a patient insists on leaving, the PCA should be disconnected.

Definition of relief/response to therapy:

 1. A scale of 0-4 (0=none, 1=little, 2=moderate, 3=good, 4=complete)
 2. Pain scale of 0-10

Relief may be defined as a score of 2 or greater and a pain intensity reduction of at least 50-60% from the upper end of the pain scale.

2.  Improvement of Pain:

When stable pain relief has been achieved, gradually reduce dose no more than 10-20% at a time unless there has been a significant improvement in pain.  After doses are reduced to 1/3 to 1/4 of their initial level, consider switching to oral opioid.  If using an oral opioid and decreasing dose, it is better to decrease the dose than to decrease the frequency of administration.  Some patients have immediate resolution of pain while other individuals have a more gradual improvement that extends over a week.

Opioid Side Effect Monitoring:

Sedation Scale
S:  Sleeping, easily aroused:  no change
1:  Awake and alert: no change
2:  Occasionally drowsy, easy to arouse: no change
3:  Frequently drowsy, arousable, drifts off to sleep during conversation: decrease or discontinue opioid
4:  Somnolent, minimal or no respone to stimuli: discontinue opioid and consider naloxone; measure O2 sat.

Pruritus
1. Benadryl or Hydroxyzine PO scheduled.  Parenteral benadryl or hydroxyzine is indicated if patient does not tolerate oral meds, ie because of nausea/vomiting.
2. Altenative regimen:  provide non-sedating antihistamine, combined with scheduled ranitidine bid.  May provide additional prn or scheduled benadryl or hydroxyzine.
3. Oxycodone:  When switching to oral medications, this may be an alternative for those who experience pruritus with morphine.  However, oxycodone/oxycontin cost more.  Some patients also experience pruritus with oxycodone/oxycontin.  Evaluate cost/benefit of regimens.

Prevention and treatment of opioid-induced constipation

Identify and treat precipitating factors
1. Dehydration:  Due to hyposthenuria, most patients experiencing painful crisis are dehydrated.  If dehydration is not treated sufficiently with oral hydration, supplement with parenteral fluids.  Monitor for fluid overload/CHF.
2. Acidosis:  An alkali (eg, Na Bicarbonate) is indicated for documented metabolic acidosis
3. Hypoxia:  Oxygen is given for documented hypoxia over steady state.  Incentive spirometry 10 inspirations Q 2 hours while awake.
4. Infection:  Assess and treat as indicated.  Assess for acute chest syndrome in patients presenting with any of the following symptoms:  cough, acute shortness of breath, fever, hypoxia, chest/back/or abd pain, new pulmonary infiltrates (chest x-ray may initially be normal).
5. Stress:  Involve social supports

Transfusions:  Recommendations are for patients with homozygous  SS disease.  Transfusions should be used as sparingly as possible and for specific indications.

Types of Blood products:  Blood should be leukocyte reduced by filtration to decrease alloimmunization to leukocyte antigens.

1. Simple transfusions are indicated when increased oxygen carrying capacity is desired, but no significant decrease in HgS is required: symptomatic anemia, sequestration crisis, aplastic crisis, accelerated hemolysis, blood loss, preoperative preparation.

2. Exchange Transfusions:  Acute chest syndrome, cerebrovascular disease, priapism, some instances of refractory pain crisis, occasionally for preoperative preparation

Exchange transfusion may be done manually or by an automated method (call the infusion center, 3-8369).  The automated method is quicker and more efficient, but requires a large-bore intravenous catheter (eg, a dialysis catheter). In emergencies, the automated transfusion is preferred.

Preoperative preparation Anemic patients with SCD-SS should be transfused to a Hg of 10g/dL before undergoing general anesthesia and surgery. In SCD-SC and other milder forms of SCD in which baseline Hg levels are usually high, preoperative transfusions may require red cell exchange.  Transfusion is recommended for surgery on the posterior segment of the eye, even when done under local anesthesia in a nonanemic patient.  Transfusion is not needed for laser surgery of the eye.

Priapism usually offered to patients who demonstrate minimal response to conservative management.  Clinical experience has shown variable success of RCT in acute priapism.  Exchange transfusion in acute priapism has been associated with neurologic events.

3. Equivocal indications Intractable or frequent painful events, preparation for infusion of contrast media, chronic leg ulcers, complicated pregnancy.

4. Transfusion is not indicated for:  Chronic steady state anemia, uncomplicated acute painful crises, minor surgery not requiring prolonged general anesthesia, aseptic necrosis of the hip or shoulder (except when surgery is required), uncomplicated pregnancy.

Iron Overload:  If ferritin levels exceeds 2,000 ng/mL and chronic transfusions are required, chronic chelation therapy using Desferal should be considered.  Patient compliance with this is often an issue.  Although intermittent Desferal given with blood transfusions does not result in negative iron balance, it may benefit patient by limiting further iron accumulation.  Desferal 1-2Gm may be given with blood transfusions.

Hydroxyurea Therapy:  Hydroxyurea increases fetal hemoglobin synthesis.  The effects of hydroxyurea therapy are not immediate.  In responsive patients, an increase in fetal hemoglobin occurs after 8 to 24 weeks and the MCV will increase from baseline.  Not all sickle cell patients respond to hydroxyurea.  In responsive patients, episodes of sickle crisis decrease by up to 50%. Successful hydroxyurea therapy requires a compliant patient and close monitoring for toxicity.
 

REFERENCES:

Benjamin, LJ, Swinson, GI, Nagel, RL.  Sickle cell anemia day hospital:  an approach for the management of uncomplicated painful crisis.  Blood 2000; 95:1130-1137.

Benjamin, LF, Dampier, CD, Jacox, AK et al.  (1999), Guideline for the Mangement of Acute and Chronic Pain in Sickle-Cell Disease, APS Clinical Practice Series, No. 1.  Glenview, IL:  American Pain Society.

Charache, S., Terrin, M., Moore, R., Dover, G., et al.  Effect of Hydroxyurea on the frequency of painful crises in sickle cell anemia.  The New England Journal of Medicine 1995;332:1317-1322.

Management and Therapy of Sickle Cell Disease: Transfusions.  NIH Publication No 95-2117, Revised December 1995.  Provided by Sickle Cell Information Center at Grady Health System, Atlanta, GA.

Ohene-Frempong,K.  Indications for Red Cell Transfusion in Sickle Cell Disease.  Seminars in Hematology 2001; 38(1) Suppl 1: 5-13.

Rackoff, W., Ohene-Frempong, K., Month, S., et al.  Neurologic events after partial exchange transfusion for priapism in sickle cell disease.  Journal of Pediatrics 1992;120: 882-885.

Vichinsky, E.  Consensus Document for Transfusion-Related Iron Overload.  Seminars in Hematology 2001; 38;Suppl 1; 2-4.

Vichinsky, EP., Haberkern, CM., Neumayr, L., et al.  A Comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease.  The New England Journal of Medicine 1995;333:206-213.

Wayne, AS, Kevy, SV, Nathan, DG.  Transfusion Management of Sickle Cell Disease.  Blood 1993;81:1109-1123.

Wood, AJ.  Management of Sickle Cell Disease.  Drug Therapy 1999; 340:1021-1030.
 

Reviewed December 2007