What is Sickle Cell Disease

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Pain Management in Sickle Cell DiseaseAllan
Platt PA-CThe Georgia Comprehensive Sickle Cell
Center at Grady Health SystemAtlanta, GA
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A
CureIS IN SIGHT

• Review of normal blood
• Sickle cell disease
• Pain assessment
• Pain management
• New developments

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Blood

• Blood has red cells(erythrocyctes)
• White cells (leukocytes)
• Platelets (thrombocytes)

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Red Blood Cells

• Carry oxygen from the lungs
• Carry carbon dioxide back to the lungs
• Normally live 120 days
• Contains the protein hemoglobin
• Made from iron, folic acid, vitamin B12
• Made in the bone marrow

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Red Blood Cells
Red cells look like doughnuts that are very
flexible
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Red Blood Cells - Shape
Red cells travel through very narrow blood vessels
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Red Blood Cells

• Red Cell Flow

Blood Vessel
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Red Blood Cells - Hemoglobin
Oxygen
Hemoglobin holds four oxygen molecules to take to
different parts of the body
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Red Blood Cells - Hemoglobin
There are normally 3 types of hemoglobin in the
red cell made of 2 alpha chains from chromosome
16 and 2 beta, delta, or gamma chains from
chromosome 11
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Red Blood Cell - Cycle
Red cells are made in the bone marrow
Food with iron and vitamins is digested
Red cells live 120 days in the circulation
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Red Blood Cells - Cycle
Kidney
Erythropoetin
Liver
Spleen
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Red Blood Cells - Retics

• Reticulocytes, or Retics are young red cells just
  released from the bone marrow. The Retic count
  tells us how the marrow factory is doing.

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What is Sickle Cell Disease?
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What is Sickle Cell Disease?

• An inherited disease of red blood cells
• Affects hemoglobin inside the red blood cells.
• Sickle-shaped and sticky red cells interrupt
  blood flow by blocking small blood vessels
• Tissue that has no blood flow is damaged causing
  pain

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What is Sickle Cell Disease?
The amino acid valine in one spot where
there should be glutamic acid.
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Types of Sickle Cell Disease
Hb SS Hb SC Hb S beta 0 Thalassemia Hb S beta
Thalassemia Hb SS with persistent Fetal
Hemoglobin Hb SD, SO-arab, SE
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PAIN RATES BY PHENOTYPEAdapted from Platt et
al New Engl J Med 32511, 1991.
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Diagnosis
Sickledex solubility test, is HbS present
(hours) Hemoglobin Electrophoresis (days)

Hb AA
HB AS
HB SS
Hb SC
Start
Hb A
Hb S
Hb C
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Diagnosis - Blood Smear
Sickle red cells
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Normal Shape to Sickle
Long rods of hemoglobin form deforming the red
cell
Microscope view of long rods in a sickle red
blood cell
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Normal vs. Sickle red cells
If no oxygen, then pain and damage occurs
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Clotting system is too active
Fibrin clot blocks blood flow, then pain and
damage occurs
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Sickle red cells are stickier
Sticky red cells block blood flow, then pain and
damage occurs
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Sickle Cell Video
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SICKLE BIOCHEMISTRY

• Deoxygenation
• Intracellular hemoglobin concentration
• pH (Amount of Acid in the blood)
• Temperature

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SICKLING - Hb CRYSTALS
O2
O2
O2
O2
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HYDRATION
O2
O2
H2O
H2O
O2
O2
H2O
H2O
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OSMOTIC EFFECTS ON SICKLING
Zarkowsky Hochmuth J Clin Invest 561023, 1975
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Worldwide Distribution
Hemoglobin S
Hemoglobin D
Hemoglobin C
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Trait vs.. Disease
8 10 in US Blacks have Hb S trait Hematuria is
most common Under extreme hypoxia, heat, altitude
change Splenic sequestration Pain events Sudden
Death
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Disease Complications

• Sickle cells become trapped and destroyed in the
  spleen causing Splenic Sequestion
• Anemia - hemolysis
• Pain episodes
• Gall Stones
• Strokes or aneurysms
• Kidney failure
• Pneumonia or Chest Syndrome
• Increased Infections
• Bone infarctions
• Retinopathy

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ABCs of Managing Sickle Cell Pain

• A - Assessment of the pain
• B Believe the patients level of pain
• C Complications or cause of pain
• D Drugs and distraction
• Pain Medication - WHO ladder
• E Environment, rest in quiet
• F - Fluids Hypotonic - D5W
• Fixed dosing NO PRN dosing

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Pain Assessment Requirements

• Document the following
• L Location, Radiation
• O - Other Associated Symptoms
• C Characteristics
• Is this your typical pain crisis pain?
• A - Alleviating and Aggravating Factors
• T - Timing
• E - Environment
• S - Severity - Use a pain scale
• Physical Examination
• Laboratory and X-Ray CBC, Retics. Chem, UA

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Pain Intensity Tools

• Modified Wong-Baker Faces Scale

2.5
7.5
5
0
10
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Pain Assessment - VAS

• The Visual Analog Scale is a 10 cm line
• The patient makes a mark from 0 no pain to 10
  worst pain ever
• A 10 cm ruler is used to determine the pain
  intensity

Pain score is 6.5
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Abdominal Pain - Splenic Sequestion

• Sudden trapping of blood within the spleen
• May be associated with fever, pain, and
  respiratory symptoms.
• Circulatory collapse and death can occur in less
  than thirty minutes.
• Gall stones in children and teens - cholecystitis

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Fever
Fever indicates Sepsis until proven other wise Do
cultures then treat with antibiotics covering
pneumococci Remember that the most common pain
medications mask a fever (NSAIDS, acentaminphen)
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Hand Foot Syndrome - Dactylitis
- Ages six months - two years. May be first
presentation to ER - This is treated with fluids
and pain medication. - Consider osteomyelitis
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Focal Bone Pain
Bone infarction, sickle arthritis, and aseptic
necrosis of the femur or humerus. Consider
osteomyelitis if febrile or increased WBC Xray,
bone scan, MRI may help
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Headache Strokes vs Meningitis

• Children have blocked flow
• Adults have aneurysms
• Presents with headache, weakness,
• Numbness, speech problems
• Fever or Increased WBC Meningitis
• Trans Cranial Doppler (TCD) screening can
  identify kids at risk
• Transfusion for life or BMT

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Pain Weakness, Anemia, or Jaundice
Anemia Hemolysis Increased indirect
bilirubin Aplastic crisis from Parvo B16 Low
retic count Sequestration in the spleen or
liver high retic count GI bleeding
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Chest Pain - Acute Chest Syndrome
Chest pain Infiltrate Dyspna and Hypoxia Treat
with O2, Transfusions and antibiotics Prevent
with incentive spirometry and pre-op transfusion
to Hb 10
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Anesthesia Considerations
Simple transfusion to Hb of 10 pre
op Hydration Temperature control Oxygenation Avoid
acidosis Good pain management Incentive
spirometry
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Treatment of Adult Pain Episodes

• Morphine sulfate 0.05 to 0.08 mg/kg (3 to 5 mg)
  IV q 10 minutes until pain is controlled.
  (No Demerol)
• Give the dose required to control the pain q 3
  hours IV. (NOT PRN)
• Add ketorolac 30 mg IV q 6 hours (NOT if renal
  disease or GI bleed history)
• IV D5W 250 cc/hr
• Adjuvants Hydroxyzine or promethazine for
  nausea or anxiety (low dose q6 hr

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PRN DOSING WITH RECURRENT PAIN
Modified from Melzak Sci Amer 26227, 1990
CNS or RESPIRATORY DEPRESSION
GOOD PAIN CONTROL, MINIMAL SIDE EFFECTS
Plasma Drug Concentration
RECURRENT PAIN
24
6
12
18
TIME, HOURS
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FIXED DOSES BASED ON T1/2
Modified from Melzak Sci Amer 26227, 1990
CNS or RESPIRATORY DEPRESSION
GOOD PAIN CONTROL, MINIMAL SIDE EFFECTS
Plasma Drug Concentration
RECURRENT PAIN
9
12
3
6
TIME, HOURS
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Treatment of Pain Episodes

• Treat for 8 hours admit if not better or if a
  complication is found
• Average length of stay is 4.5 days
• If able to go home give 48 hour supply of
  opiate and NSAID (no renal or GI hx)
• Return if pain increases, fever develops, no
  improvement
• Give follow-up with sickle cell clinic or
  hematologist
• Consider hydroxyurea hydrea for pain prevention

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1 year ER visits in 637 Adults
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Dependence, Tolerance, Addiction

• Pain Crisis per year
• 90 have 0 3/yr
• 5 have 3 12/yr
• 5 gt 13/yr (consume 50 resources)
• Physical Dependence
• Anyone after 7 days continuous opiate use
• Tolerance
• Anyone on continuous opiate- increased dose
  needed
• Addiction Life revolves around drug 5
• Pseudo-addiction
• Under treatment return under treatment
  return --

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Objectives of the Sickle Cell Center

• 24 Hour Urgent Care
• Comprehensive Primary Care
• Tertiary Care
• Model of Cost Effective Disease Management
• Education
• Research

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24 Hour Urgent Care

• All patients over 15, except during pregnancy or
  for acute trauma
• Treated by MD-PA, RN, Clinic Assistant using
  problem specific clinical guidelines developed
  over 15 years
• Aggressive pain and fluid management
• Admitted if not improved by 8 Hours of treatment
• Instant Medical Records
• Shadow chart and online database

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Comprehensive Primary Care

• Acute Care Team
• Pediatric Team
• Outpatient, Inpatient, Case Management
• Adult Team
• Outpatient, Inpatient, Case Management
• Hydrea Monitoring
• Leg Ulcer Care
• Stroke Prevention, TCD
• Transfusion Therapy

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10 year data 1991 - 2001

• 20,968 pain episodes
• 1,076 patients over 15 years old
• Average age 36.8 years old
• oldest patient 82
• 51 male, 49 female visits
• Pain Assessment using VAS
• Admission if
• Complication Fever, infiltrate, hct
• Return within 48 hours
• Pain not manageable after 8 hours

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80 Better in 8 Hours of Treatment 20,968
episodes over 10 years
20 Admitted, 80 went home 3988 Admissions 52
Left AMA 92 Critical Care
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Pain Crisis Episodes and Admissions per Active
Adult
Pain Episodes per active adult
3.1 Pain 0.5 Admit
Case Management

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Analgesics Used in 20,968 Pain Episodes in 1,076
Adults
Demerol
Nubain was used in 57 of pain episodes
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Education

• World Wide Web Site - The Sickle Cell Information
  Center
• http//www.SCInfo.org
• Information for providers, patients, teachers,
  employers, administrators
• Monthly E-mail Newsletter aplatt_at_emory.edu

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Research

• Bone Marrow Transplant Center - 15 Children
  Cured in Atlanta
• Hydroxyurea - First Treatment to Prevent
  Complications
• Stroke Prevention (STOP) Study
• Endothelial Adhesion - Ga Tech
• Renal Complications
• Psycho-social Interventions
• Pain Management - Nalbuphine

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Research - New Projects

• N3 Fatty Acid (fish oil)- Multi-center Trial
• Pain Assessment palm based
• Say NO to pain Nitric Oxide,
• New Medications
• Web Based Teaching
• Transition to Adulthood

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Resources

• World Wide Congress on Pain http//www.pain.com
• American Pain Society www.ampainsoc.org
• www.SCInfo.org
• www.SickleCellKids.org
• Sickle Cell Center 24 hr 404-616-3572
• www.Partnersagainstpain.com- Purdue Pharma
• Book Hope and Destiny
• Sickle Rap

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THE FUTURE

• Teach Patients and Parents
• Early Prevention
• Early Treatment
• Early Screening
• Better Education
• Better Treatment
• Better Pain Management
• A cure for all