Sickle Cell Information Center Guidelines

by James Eckman, M.D. and Allan Platt, PA-C

Pain episodes are among the most troublesome and frequent complications of sickle cell syndromes. The patient develops severe pain in the extremities, back, and abdomen. A sickle pain episode is both uncomfortable and frightening to the patient, however, in itself almost never results in mortality. Pain episodes may be spontaneous or occur in association with physical or psychological stress. Treatment consists of resolving precipitating events, bed rest, hydration, and appropriate analgesics.

Present Illness. Define the chief complaint, nature, location, severity, duration, and treatment of pain. Is distribution typical for patient's pain episodes? Although pain in one location can be seen with pain episodes, localized pain may suggest a complication. Specific precipitating factors such as infection, dehydration, exercise, menstruation, or stress should be documented.

Review of Symptoms. Specifically exclude symptoms of infection such as fever, chills, cough, vomiting, diarrhea, dysuria, frequency, or headache.

Past Medical History. Document hemoglobin phenotype, general health, recent hospitalizations and surgery, allergies or sensitivities to NSAIDs or aspirin, usual treatment for pain episodes and previous response to therapy, and present medications.

-General: Assess amount of distress, nutrition, hydration status.

-Pain Assessment: Evaluate pain with analog pain scale at presentation, 1 hour, 2 hours, 4 hours, 6 hours, and discharge.

-HEENT: Increased jaundice, pallor, fundoscopic, tympanic membranes, pharyngitis, nasal polyps, sinusitis.

- Neck: Lymphadenopathy, thyroid enlargement.

-Chest: Signs of pneumonia, heart failure, or localized tenderness.

-Cardiac: Venous pressure/pulse, PMI, murmur, gallop, edema.

-Abdomen: Bowel sounds, change in liver/spleen size, local tenderness, rebound.

-GU/Pelvic: CVA or suprapubic tenderness, priapism, discharge, cervical tenderness with motion.

-Extremities: Local tenderness, erythema, swelling, joint effusion, edema, leg ulcers - active and healed.

-Neurological: Meningeal signs, cranial nerve abnormalities, weakness, paresthesias, DTRs, coordination.

- Minimum Evaluation. CBC with differential, platelet and reticulocyte count, and urinalysis. Consider a Chem profile including electrolytes, BUN, Creat, AST, bilirubin if the pain is unusually severe

-Additional Evaluation. Urine culture if urinalysis or urinary tract infection suggested by history or physical examination. Amylase if abdominal pain is present. ECG for chest pain, palpitations, or congestive heart failure. Arterial blood gases for unusually low O₂ saturation on pulse oximetry, dyspnea, chest syndrome, or suspected hypoxia. Do chest x-ray for productive cough, dyspnea, chest pain, or cough with fever, WBC over 15,000/left shift, or unusually low O₂ saturation on pulse oximetry. Areas with localized pain or swelling should be x-rayed.

- Pain Episode. The diagnosis of sickle cell pain episode (crisis) is clinical and must be based on history alone. Significant changes in physical findings or laboratory values are only seen in precipitating or concomitant complications. A complication needs to be excluded if localized or atypical pain is present. See specific protocols.

-Infection. Fever over 38^oC, chills, WBC over 20,000 or left shift, and local swelling, or erythema all suggest infection or some other inflammatory complication as a precipitating event (See Fever ).

-Chest Syndrome. Chest pain may indicate pneumonia or pulmonary infarction, especially if fever is present (See Chest pain)

- Abdominal Pain. Diffuse abdominal pain may be present in uncomplicated sickle episode. Bowel sounds are normal or increased and rebound is absent. Severe or localized pain, decreased bowel sounds, increase in liver or spleen, nausea, vomiting or diarrhea suggest complication (See Abdominal pain )

-Bone-Joint Pain. Localized bone or joint pain especially with swelling, erythema, or warmth suggests osteomyelitis, bone infarct, septic arthritis, or gout. Acute, mono-articular arthritis may accompany pain crisis but this also is a diagnosis of exclusion (See Bone pain )

-Headache. Headache or neurologic symptoms suggest meningitis, infarctions, subarachnoid hemorrhage (See Neurologic symptoms )

-Anemia. Falling hematocrit suggests aplastic or sequestration crisis (See anemia )

Patient must be treated with bed rest, hydration, analgesia, and therapy for precipitating complications. This protocol defines treatment options for the majority of patients presenting with uncomplicated pain episode. Aggressive hydration and prompt control of pain with adequate analgesic medications given on a schedule consistent with drug duration of drug action will arrest uncomplicated episode. If treatment can be given for 8 hours in an outpatient observation setting, over 80% of patients will have reduction in pain to a level that can be treated at home with rest, hydration and oral antibiotics. Patients should be admitted if there are other complications, pain persists for more than 8 hours despite adequate therapy, or outpatient therapy fails and the patient returns for further treatment within 48 hours. More prolonged inpatient therapy and monitoring is almost always indicated if any of these three criteria are present.

-Failure to be pain free with 8 hours of outpatient treatment.

-Return for further therapy within 48 hours of previous inpatient or outpatient treatment of a pain episode.

- Pain episode plus:

- Infection - Documented infection, WBC over 20,000 or left shift, or fever over 38^oC.

- Significant hypoxia or acidosis.

- Pregnancy.

- Cardiac decompensation.

- Priapism.

- Thrombo-embolic events in lungs and CNS or bone infarctions.

- Aplastic or hyperhemolytic crisis (Fall in hemoglobin of more than 1 gram/dl over baseline; see anemia protocol).

- Hepatic syndromes or cholecystitis (See abdomen protocol).

Oral hydration by forcing fluids if patient is alert, not nauseated, or significantly dehydrated.

Intravenous hydration with D₅W at 250 cc/hr (children 5cc/kg/hr) for 4 hours in the absence of CHF, renal failure, or hyponatremia. Change to D₅W or D₅W with 1/4 or ½ Normal Saline at a slower rate, 125 cc/hr (children 1 to 2 cc/kg/hr) for second and subsequent liters based on electrolytes. If venous access cannot be obtained, use oral hydration. Do not start I.V.s in the legs unless there in an arrest situation because of the high frequency of leg ulcers after I.V.s attempted in the ankle area.

Medications listed here are usually initiated as home therapy before presenting to health care providers.

-Aspirin 6.5 to 10 mg/kg P.O. or rectally q 4 hours aspirin should be avoided in febrile children especially if symptoms suggest chicken pox or flu syndrome because of the risk for Reye's syndrome.

-Acetaminophen 10 mg/kg q 4 hours with a maximum of 5 dose/24 hours.

-Tylenol #3, 1 to 3 tabs P.O. q 4 hours, for 48 hours in older children and adults.

-Vicodin, 1 to 2 tabs P.O. q 4 hours for 48 hours in older children and adults.

- Ibuprofen (Motrin) 800 mg or other fast acting NSAID P.O. q 6 to 8 hours or Aspirin 600 mg P.O. q 4 hours for adult patients who have no contra-indications. NSAIDs are not approved and aspirin should be avoided in febrile children because of the risk for Reye's syndrome.

-Parenteral NSAID: Ketorlac (Toradol) for adults over 50 kg give 30 mg I.V. q 6 hours for 5 days maximum. In adults less than 50 kg, give 15 mg I.V. as a loading dose and then 15 mg I.V. q 6 hours. The lower dose should be used in individuals over 65 years old and those with renal insufficiency. At present, 120 mg is the maximum total daily dose. Ketorlac must be stopped after 5 days because of the potential for toxicity.

-Oral NSAID of choice and patient tolerance should supplement any treatment plan of adults not using Ketorlac.

- Parenteral Narcotics:

- Morphine sulfate 0.1 to 0.2 mg/kg I.V. (up to 15 mg) q 3 hours.

- Nalbuphine HCl (Nubain), 0.3 mg/kg up to 20 mg I.V. q 3 to 4 hours. Total daily dose should be limited to 160 mg. Do not use in patients that may be physically dependent on narcotics because withdrawal may be precipitated. Do not use with agonist narcotics because Nalbuphine may block their analgesic action. Do not use with agonist narcotics because Nalbuphine may block their analgesic action. Note: Do not mix Phenergan with Nalbuphine in the same syringe.

- Buprenorphine HCl (Buprenex) 0.3 to 0.6 mg initially, followed by 0.3 mg I.M. q 6 to 8 hours. Not approved for use in children. Overdose may require intubation since Naloxone may not reverse respiratory depression. Use with caution in patients who may have physical dependence on narcotics. Do not use with agonist narcotics because it may block their analgesic action

- Add hydroxyzine HCl (Vistaril) 25 mg q 6 hours or, if allergy to hydroxyzine HCl exists, use promethazine HCl (Phenergan) 12.5 mg I.M. q 3 hours for individuals that have vomiting with narcotics.

- Add Benadryl 25 to 50 mg q 6 hours with morphine to prevent itching

- Patients on Methadone Treatment.

- Methadone 10 mg I.V. followed by 25 mg P.O. q 6 hours. Use 25% of the patient's usual daily dose P.O. q 6 hours if the patient is on a confirmed daily maintenance dose of more than 30 mg. Oral dose over 24 hours should equal or exceed their usual daily dose.

- Patient Controlled Analgesia (PCA).

- PCA is an acceptable form of pain treatment that may have advantages in the treatment of pain episodes. The patient must understand the principles of PCA and be willing to assume the responsibility for managing their pain. They and their significant others need to understand that only the patient can administer medication through the PCA pump. In general, most patients with sickle pain episodes require a continuous infusion plus demand doses for breakthrough pain. The use of a loading dose via PCA or by IV bolus while the PCA is being set up is required. The amount of the loading dose, the amount of the continuous infusion, and the amount and frequency of the demand dose is individualized and based on the patient’s past treatment history.

Morphine PCA is the preferred therapy although some centers use meperidine and hydromorphone for PCA. Morphine concentration of 5 mg/ml is used to treat adults because they generally need relatively high doses to control the pain. Loading doses of morphine up to 0.05mg/kg q 15 minutes times 4 may be given based on need. Demand doses of 0.018 to 0.04 mg/kg/dose with a 5 to 15 minute lockout are an usual range for sickle patients. Continuous infusion doses, if necessary, may be given at night or around the clock. The usual dose ranges are between 0.01 to 0.04 mg/kg/hour. One hour or four hour limits should be calculated so that the patient can get treatment for the entire period. That is the limits should be based on the sum of the maximum demand dose plus the continuous infusion dose.

Standard orders should provide for proximity to nursing station, narcan at the bedside, and resuscitation bag in proximity. All other narcotics and sedatives should be stopped except seizure medications. Diphenhydramine, promethazine, or hydroxyzine may be given to control nausea and itching but their doses must be reduced to prevent over sedation. Vital signs should be taken every 15 minutes for the loading doses and for the first hour of PCA then every four hours. PCA should be immediately stopped and the physician notified for over sedation, respiratory rate of less than 12, use by other than the patient, and loss of IV access.

The PCA use and degree of pain control should be re-evaluated frequently and at least every 24 hours. Orders should be rewritten every 48 hours. Once the pain episode is improving the infusion should be tapered then the amount of the demand dose reduced. Oral analgesic are started and the PCA discontinued when the patient’s pain can be managed with oral analgesia alone.

The amount of medication and frequency of administration should be adjusted to achieve pain control. A regular schedule of administration will better maintain blood levels and, therefore, provide pain control than will dose but not the frequency. When the total daily dose is one-half that required to control pain, switch to an oral medication based on the planned take-home medications.

All patients receiving narcotic analgesics on an appropriate regular schedule of administration need to be observed for over sedation and respiratory depression. For over- sedation, decrease the amount of narcotic analgesic and discontinue concurrent hydroxyzine or promethazine. For respiratory depression, monitor blood pressure and administer Naloxone 0.01 mg/kg in children and 0.1 to 0.2 mg in adults I.V. q 3 minutes times 2 doses. For patients on regular narcotics, or children, dilute 1:10 and give slowly. Emergency support equipment needs to be present and doses of naloxone repeated to maintain respiratory rate and blood pressure. Dilute and use with extreme caution in patients on continuous narcotics or those thought to be addicted.

As a rule, the patient should be managed with a limited supply of oral analgesics consistent with the parenteral treatment protocol used in initial treatment. A 48 hour supply should be sufficient.

- Short Acting. Ibuprofen (Motrin) 400 P.O. q 8 hours

- Aspirin 600 mg P.O. q 4 hours

- Long Acting. Salsalate (Disalsid) 750 mg 2 tabs P.O. B.I.D.

Sulindac (Clinoril) 200 mg P.O. B.I.D.

-Acetaminophen (300 mg) with codeine (30 mg) [Tylenol #3] ii (two) Tabs. P.O. q 3-4 hours P.R.N. pain. Maximum # 30.

- Acetaminophen (500 mg) with hydrocodone (5 mg) [Vicodin] I (one) tab P.O. q 4 - 6 hours P.R.N. pain. Maximum # 12.

-Morphine sulfate pentahydrate controlled-release tablets (30 mg) [MS Contin] I or ii Tab P.O. q 8 - 12 hours P.R.N. pain Maximum # 6.

-Morphine sulfate liquid (10 mg / 5 ml) 15 ml (I tablespoon) P.O. q 4 hours P.R.N. pain. Maximum 180 ml.

- Oxycodone HCL controlled release tablets (OxyContin) 10 mg I or ii Tab P.O. q 12 hours. Maximum #6.

- Oxycodone HCL immediate release tablets (OxyIR) 10 mg I or ii Tab P.O. q 4 -6 hours P.R.N. breakthrough pain. Maximum #12.

- Patients that have been on narcotics for more than a week may need a tapering schedule of narcotic analgesics to prevent physical withdrawal after abrupt stopping of narcotics.

-Methadone HCl (5 mg) I (1) Tab. P.O. q 6 hours P.R.N. pain. Maximum # 8.

The inpatient management of pain episode includes treatment of complicating medical problems, bed rest, intravenous hydration, and adequate narcotic analgesia. Remember all that hurts is not pain episode! During the initial treatment period until the patient is definitely improving, pain medication should be given on a fixed not P.R.N. schedule. This will both assist the nurses in their interactions with the patient and will decrease the reinforcement of drug seeking behavior.

- Bed rest.

- Treat underlying infections.

-Parenteral and oral narcotics as outlined under the outpatient treatment of moderate to severe pain episode.

- Patients being treated with morphine may benefit from concurrent use of long-acting oral and parenteral morphine. MS Contin 30 to 60 mg P.O. every 12 hours is given on a fixed schedule based on the use on the prior day remembering that the equivalent oral dose is three times the parenteral dose. The patient also has parenteral morphine available P.R.N. for break-through pain. The MS Contin dose is adjusted daily based on the prior 24 hour use of P.R.N. doses.

Discharge Medications

Patients should be treated until they are essentially pain free so they can be discharged with a minimal supply of oral narcotics. The recommended take-home medications, duration of treatment, and maximum number of pills are the same as for the outpatient treatment of pain episode.

Nursing Considerations

 Assess pain status (rate, locations, characteristics, precipitating factors).

For maximal effectiveness administer pain medications on schedule as ordered (Remember that pain behavior and pain score could be divergent).

Incorporate non-pharmaceutical measures such as relaxation techniques, meditation, reading, music, arts/crafts, other forms of distraction, and the use of other coping mechanisms.

 Emphasize the importance of hydration, and encourage fluids.

Explain to patient/care giver that the following could trigger sickle cell pain crisis: - dehydration, cold temperatures, vigorous exercise and stress.

Emphasize the importance of keeping routine health maintenance clinic and follow-up appointments.

Encourage patient to maintain communications with all health professionals.

 Instruct patient in goal setting to normalize life style and place pain in perspective.

 Encourage bedrest and relaxation.

 Educate patient/family about medications, adverse reactions, drug interaction, expected outcomes and to report symptoms immediately.

Stress the importance of at home early treatment for pain crisis (rest, warm baths, relaxation, hydration, analgesia based on pain score).

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Last modified: June 12, 2001