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Sickle cell disease.Therapeutics


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Sickle cell disease.Therapeutics

  1. 1. Dr. Afzal Haq Asif Associate Professor COCP, KFU Dec 02, 2013 Dr Afzal Haq Asif 1
  2. 2. Case A 20 years old male reported with history of delayed puberty, decreased growth, severe joint pain, severe weakness and cough. He also have defective vision Past history reveals episodes of jaundice, severe body aches and pains, and gall stones In his childhood he used to have frequently fever swelling of the hands and feet and pain in the chest, abdomen, limbs, and joints and nosebleeds and frequent upper respiratory infections Dec 02, 2013 Dr Afzal Haq Asif 2
  3. 3. Case O/E; Decreased growth, delayed signs of puberty severely anemic, mildly jaundiced, ulcers on right leg, inflamed gums Enlarged spleen. Temp 39.1°C, diaphoretic, and uncomfortable. HR of 90, BP 116/84 mm Hg, RR 26 O2 Sat 89% and improved to 94% with 6 L/min via face mask. Family history: similar problem in one of his cousin who died at the age of 30, who used to receive blood transfusions Dec 02, 2013 Dr Afzal Haq Asif 3
  4. 4. Case WBC of 17 500/μL 62% neutrophils 25% lymphocytes 9% monocytes 2% eosinophils 1% basophils 1% atypical lymphocytes. Hb was 8 g/dL reticulocyte 25% platelet 206 000/μL. Dec 02, 2013 Dr Afzal Haq Asif 4
  5. 5. Case Which lab test you will advise? What is most probable cause of patients problem? What complications the patient may have? Design therapeutic objectives for this patient? Dec 02, 2013 Dr Afzal Haq Asif 5
  6. 6. Dec 02, 2013 Dr Afzal Haq Asif 6
  7. 7. Hemoglobin: Introduction Normal: alpha gene at Chr 16, beta at Chr.11 HbA: 2 Alfa + 2 beta 97-98% Hb A2: 2 Alfa + 2 delta 2-3% Hb F; 2 alfa + 2 gamma >1% Hb S: Glutamic acid at 6 in beta chain replaced with Valine HbC: ……………………………………………………………………….Lysine Thalassemia: Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin Alfa: less alfa chain Chr.16 Beta: Chr.11: less beta, beta thalassemia minor  or no beta, all alfa chain beta thalassemia major : Dec 02, 2013 Dr Afzal Haq Asif 7
  8. 8. SICKLE CELL DISEASE An autosomal recessive genetic disease of Hb synthesis Result of a single–amino acid substitution in the β-globin chain of the Hb molecule, valine for glutamate at position 6 Sickle cell trait: Pt. with hetrozygous genotype Epidemiology in KSA:  “The prevalence of SCD in Saudi Arabia varies significantly in different parts of the country, with the highest prevalence is in the Eastern province, followed by the southwestern provinces. The reported prevalence for sickle-cell trait ranges from 2% to 27%, and up to 2.6% will have SCD in some areas”  Ann Saudi Med. 2011 May-Jun; 31(3): 289–293. Dec 02, 2013 Dr Afzal Haq Asif 8
  9. 9. Comparison with USA African Americans: SCD: 0.3% Saudia: Saudia: SCT: 8.0% Dec 02, 2013 Dr Afzal Haq Asif 2.6% 2-27% 9
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  14. 14. Pathophysiology  Normal Hemoglobin A: two alpha and two beta chains, 96-97%  Glutamic acid is on the 6th position of the Beta chain  Hemoglobin S: Chr.11  Due to a one point mutation, glutamic acid is replaced by valine at position 6 in beta chain  HbS: during deoxygenation   Polymerize Crystellize   in RBC’s…………………….leading to………………….. Sickling of Cells: RBC cell membrane changes: activate coagulation pathways  Rate of polymerization and sickling augmented by:  Hypoxia, deoxygenation  Infections,  Acidosis,  Physical exercise,  Vasoocclusion due to cold as well as hypertonic dehydration Dec 02, 2013 Dr Afzal Haq Asif 14
  15. 15. Clinical Presentation Sickle cell trait (SCT) Carrier, recessive Rare painless hematuria; normal Hgb level; heavy exercise under extreme conditions may provoke gross hematuria and complications Sickle cell anemia (SCA) Anemia Chronic hemolytic anemia: jaundice, gall stone, splenomegaly Acute Pain crises, Microvascular disruption of organs (spleen, liver, bone marrow, kidney, brain, and lung), gallstone, priapism, leg ulcers, anemia (Hgb 7-10 g/dL) Dec 02, 2013 Dr Afzal Haq Asif 15
  16. 16. Clinical Presentation Sickle cell hemoglobin C: Painless hematuria Aseptic necrosis of bone: less common Vaso-occlusive crises less common, occur late in life Pregnancy-related problems; mild anemia (Hb 10–12 g/dL) Sickle cell β-thalassemia Rare crises; milder severity than sickle cell disease because of production of HbA; Hb 10–14 g/dL with micro-cytosis Sickle cell Alfa-thalassemia or β0 Thalassemia No HbA production; severity similar to sickle cell anemia; Hb 7–10 g/dL with microcytosis Dec 02, 2013 Dr Afzal Haq Asif 16
  17. 17. Diagnosis Laboratory findings RBC’s: 5-50 % sickled Low hemoglobin; 7-10%; HbA; 0%; HbS 85-98% Increased reticulocytes: 10-25%, platelet, and leukocyte counts; and sickle forms on the peripheral smear Routine neonatal screening programs: DNA from fetal cell for mutation Dec 02, 2013 Dr Afzal Haq Asif 17
  18. 18. Goals of Therapy To reduce Hospitalizations, Complications, Mortality Dec 02, 2013 Dr Afzal Haq Asif 18
  19. 19. Treatment GENERAL PRINCIPLES  No Treatment for the primary disease  Lifelong multidisciplinary care  general measures,  preventive strategies,  treatment of complications and acute crises. Routine immunizations plus influenza, meningococcal, and pneumococcal vaccinations. Prophylactic penicillin for children with sickle cell disease until they are 5 years old.  Penicillin V potassium, 125 mg orallytwice daily until 3 years of age and then 250 mg twice daily,  Benzathine penicillin, 600,000 units intramuscularly every 4 weeks. Folic acid, 1 mg daily, is recommended in adult patients, pregnant women, and patients of all ages with chronic Dec 02, 2013 hemolysis. Dr Afzal Haq Asif 19
  20. 20. Fetal hemoglobin stimulators and other strategies  Hydroxyurea, a chemotherapeutic agent  Stimulate HbF by stimulating erythropoiesis  In patients with frequent painful episodes, severe symptomatic anemia, acute chest syndrome, or other severe vasoocclusive complications.  Butyrate and 5-aza-2-deoxycytidine.  Chronic transfusion every 3 to 4 weeks The optimal duration is unknown  to prevent stroke and stroke recurrence in children.  Maintain HbS of less than 30% of total hemoglobin..  Risks include, hyperviscosity, viral transmission (requiring hepatitis A and B vaccination), volume and iron overload, and transfusion reactions.  Allogeneic hematopoietic stem cell transplantation  The only therapy that is curative.  Best candidates are     Dec 02, 2013 younger than 16 years of age, With severe complications, Have HLA-matched donors. Risks: mortality, graft rejection, and secondary malignancies Dr Afzal Haq Asif 20
  21. 21. Stem Cells in the Treatment of SCD Skin stem cells cure mice of sickle cell anemia Success is proof that technique has potential to cure disease Dec 02, 2013 Dr Afzal Haq Asif 21
  22. 22. Complications Acute Chest Syndrome Septicemia Stroke or CVA Acute splenic sequestration crisis (ASSC) Aplastic Crisis VasoOcclusive pain: Sickle cell crisis Severe pain is an emergency called acute sickle cell crisis Osteomyelitis Dec 02, 2013 Dr Afzal Haq Asif 22
  23. 23. Sickle Cell Crisis Rapid diagnosis and treatment are necessary to minimize morbidity and mortality. Dec 02, 2013 Dr Afzal Haq Asif 23
  24. 24. Case 1 A 16-year-old boy with a history of SCD presented to the ED with a 3-day history of fever, cough, and SOB. Five days prior, he had been evaluated and treated for severe pain in his legs and arms. He complained of persistent and worsening pain in both his lower extremities and pain in his chest, in spite of oral narcotic therapy. Dec 02, 2013 Dr Afzal Haq Asif 24
  25. 25. Case 1 His medical history included multiple, vasoocclusive, painful crises, including an episode of priapism, and he had received multiple blood transfusions over his lifetime. Dec 02, 2013 Dr Afzal Haq Asif 25
  26. 26. Case -1 On examination Temp 39.1°C, diaphoretic, and uncomfortable. HR of 80, BP 116/84 mm Hg, RR 26 O2 Sat 89% and improved to 94% with 6 L/min via face mask. Conjunctivae were icteric Mucous membranes were moist Dec 02, 2013 Dr Afzal Haq Asif 26
  27. 27. Case 1 Cardiovascular II/VI systolic ejection murmur. labored respiration with suprasternal and intercostal retractions. decreased breath sounds in the right midzone and lower zone, and scattered crepitations on the right side. no lower extremity edema Abdominal examination Normal CNS Normal Dec 02, 2013 Dr Afzal Haq Asif 27
  28. 28. Case 1 500/μL WBC of 17 62% neutrophils 25% lymphocytes 9% monocytes 2% eosinophils 1% basophils 1% atypical lymphocytes. Hb was 8 g/dL reticulocyte 25% platelet 206 000/μL. ABG on room air •PO2 59 mm Hg •PCO2 29 mm Hg •pH 7.32 •HCO3 13 mmol A chest x-ray right lower-lobe consolidation with a moderate right pleural effusion. Dec 02, 2013 Dr Afzal Haq Asif 28
  29. 29. Case-1 In the ED, he received  antipyretics  supplemental oxygen  cefotaxime 2 g IV  packed red blood cell transfusion was initiated after 20 mL/kg of normal saline was infused Over the next hour, while waiting for a bed to become available in the intensive care unit, the nurse noticed that the patient's oxygen saturation continued to worsen, and he was hypoxic even on supplemental oxygen of 12 L/min via nonrebreather mask. He underwent emergency intubation A diagnostic pleural tap was performed which demonstrated an exudative fluid. The resulting Gram stain and culture were negative. Dec 02, 2013 Dr Afzal Haq Asif 29
  30. 30. Case 1 What is it Dec 02, 2013 Dr Afzal Haq Asif 30
  31. 31. Acute Chest Syndrome.1 1 of the most serious and life-threatening complications of SCD Leading cause of mortality and morbidity in affected patients, since the impact of more effective antimicrobials and the pneumococcal vaccine Caused by a vasoocclusive crisis involving the pulmonary vasculature. Not distinguishable from pneumonia Dec 02, 2013 Dr Afzal Haq Asif 31
  32. 32. Acute Chest Syndrome.1 Dx New infiltrate on chest radiograph in combination with at least 1 clinical sign or symptom Chest pain Cough Wheezing Tachypnea •Fever and cough are the most common in children •chest pain, sob, and chills are common in adults. Fever Dec 02, 2013 Dr Afzal Haq Asif 32
  33. 33. Acute Chest Syndrome.1 Common causes Pulmonary infection: Mycoplasma pneumoniae more commonly associated with acute chest syndrome Thromboemboli Fat emboli Rib infarction Possible causes Iatrogenic: excessive hydration or narcotic use Infection and fat emboli were the most common identifiable causes. Vichinsky EP, Neumayr LD, Earles AN, et al. Causesand outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group [published erratum appears in N Engl J Med 2000; 343:824]. N Engl J Med .2000;342:1855–65 Dec 02, 2013 Dr Afzal Haq Asif 33
  34. 34. 1.Acute Chest Syndrome Therapeutic Modalities Supportive measures  Oxygen for hypoxia  Appropriate hydration  Appropriate pain control Antibiotics: third-generation cephalosporin + macrolides Transfusion therapy:  Reports of dramatic improvement in clinical condition after initiation of transfusion   Simple transfusion Exchange transfusion Experimental therapy  Nitric oxide  Corticosteroids Bodo I, Khoury H, Blinder M. Rapid resolution of the acute chest syndrome of sickle cell disease after automated red cell exchange. Blood 1997;90 Suppl 1:23b Dec 02, 2013 Dr Afzal Haq Asif 34
  35. 35. 2.Septicemia SCD pts have impaired immunologic function that is caused by splenic dysfunction. Impairment of splenic function can occur in infants as young as 3 months. High risk for encapsulated organisms such as S pneumoniae and H influenzae. Recommended antibiotic  Third-generation cephalosporin; ceftriaxone, or cefotaxime  Vancomycin should be added to protect against penicillinresistant strains of S pneumoniae if suspected until culture results become available  All SCD patients with fever must be managed with extreme caution because of the risk of overwhelming bacteremia which can rapidly lead to septic shock Dec  02, 2013 Dr Afzal Haq Asif 35
  36. 36. 3.Stroke or CVA Major complication of SCD Is a leading cause of death in both and disability children and adults The most common is blockage of the intracranial internal carotid and middle cerebral arteries.  Patients with stroke usually present with obvious signs such as acute hemiparesis, aphasia or dysphasia, seizures, severe headaches, cranial nerve palsy, altered mental status, or coma. The most common tends to be hemiparesis. Can be very subtle, such as a slight limp Dec 02, 2013 Dr Afzal Haq Asif 36
  37. 37. Treatment: Stroke or CVA Initial therapy is exchange transfusion in an ICU setting to reduce Hb S to less than 30% of total Hb. After acute clearance of symptoms should be started on a long-term transfusion therapy. If not on a long-term transfusion program have an 80% chance of recurrent stroke within 3 years of the initial event Long-term transfusion involves regularly scheduled blood transfusions aimed at reducing the percentage of Hb S and not at normalizing the Hb level.  Dec 02, 2013 Dr Afzal Haq Asif 37
  38. 38. A 44-year-old diabetic presented to the ED complaining of nonexertional dyspnea and severe back pain for 12 hours before presentation. The patient reported malaise, fatigue, weakness that started 3 days before, chronic blurred vision, insomnia, and anxiety. The remainder of the review of systems was unremarkable. Dec 02, 2013 Dr Afzal Haq Asif 38
  39. 39. Case 2 O/E HR RR Temp BP 37C o2 sat 101 bpm 31/min 148/62 mm Hg 99%. The patient was awake, alert, and oriented He was motionless to avoid back pain. Dec 02, 2013 Dr Afzal Haq Asif 39
  40. 40. Case 2 O/E Normal S1 and S2 Chest Normal Strength was 4/5 in all 4 extremities. Deep tendon reflexes were normoactive. Normal flexor plantar response was obtained, and no meningismus Dec 02, 2013 Dr Afzal Haq Asif 40
  41. 41. Case 2 WBC 11.2 × 109/L (with no abnormalities in differential count) Hg of 9.4 g/dL HCT of 26.3% MCVof 76.7 Femtoliters (fL) MCH 27.3 pg Platelets of 144 × 109/L. Dec 02, 2013 Dr Afzal Haq Asif 41
  42. 42. Case 2 • Blood glucose • AST • ALT • ALK Ph Total bilirubin level of 79 U/L 30 of U/L 475 U/L 2.3 mg/dl Direct bilirubin level of 0.8 mg/dL 267 mg/dL ESR 54 mm/h C-reactive protein level of 2.3 mg/dL. ECG Normal MRI of the lumbar spine was Normal Dec 02, 2013 Dr Afzal Haq Asif 42
  43. 43. Case 2 Despite aggressive narcotic treatment of back pain, the pain continued to increase CT abdomen: an enlarged spleen 1 hour later hypotension of 90/50 mm Hg. The new CT scan of the abdomen revealed an increasing splenomegaly compared with the previous one Dec 02, 2013 Dr Afzal Haq Asif 43
  44. 44. Case 2 Despite transfusion therapy, the patient's Hb progressively dropped to a level of less than 4 mg/dL over the course of 3 hours, with thrombocytopenia (<50 × 109/L). immediately transferred to an ICU. altered mental status. Airway protection with intubation and mechanical ventilation were initiated. As the patient was rapidly deteriorating, an emergent splenectomy was performed The patient recovered every organ function and, 6 months later, has resumed his normal activities Dec 02, 2013 Dr Afzal Haq Asif 44
  45. 45. 4.Acute splenic sequestration crisis (ASSC)  Clinical Presentation:  Sudden impounding of red blood cells by the spleen  Characterized by the rapid fall in hemoglobin concentration, rise in reticulocyte count, and splenomegaly  Requires prompt recognition and treatment.  In the adult patient, ASSC is extremely rare.  Hypotension caused by large volumes of blood (mainly sickled cells) entrapped in the spleen.  Hb levels may fall acutely more than 2 g/dL less than the patient's normal value, causing circulatory compromise Treatment:  Prompt diagnosis and therapy with RBC transfusions  Surgical splenectomy may be indicated in certain patients to prevent recurrences Dec 02, 2013 Dr Afzal Haq Asif 45
  46. 46. Aplastic Crisis.5 Temporary cessation of red cell production with a corresponding decrease in the reticulocyte count. Approximately 80%, are thought to be caused by human parvovirus B19 infection Diagnosis is made by comparing baseline blood and reticulocyte counts to those obtained during the acute illness. Sign Symptoms: , tachypnea, tachycardia, or hypoxia Treatment:  Simple blood transfusion to raise serum Hb back to the patient's baseline and to prevent heart failure secondary to severe anemia.  Parvovirus B19 is contagious, affected persons should be isolated from pregnant women, who are at risk for miscarriage with infection, and from immuno-compromised patients and those with chronic illness Dec 02, 2013 Dr Afzal Haq Asif 46
  47. 47. Osteomyelitis.6 Most commonly caused by Salmonella species or Staphylococcus aureus Bone pain or joint pain with localized swelling and decreased range of motion, along with fever, should alert the physician to the possibility of osteomyelitis. Increased white blood cell count and elevated ESR Broad-spectrum antibiotic: Ceftriaxone: Dec 02, 2013 Dr Afzal Haq Asif 47
  48. 48. Priapism.7 Painful prolonged erection of the penis Caused by sickling of the red blood cells producing venous stasis in the erectile tissue of the penis. The resulting stasis causes ischemia, hypoxia, and pain. Treatment:  Initial treatment involves intravenous hydration and analgesia.  Antianxiety agents  Vasoconstrictors to force blood out of corpus cavernosum:  Phenyl ephedrine  Epinephrine  Vasodilators: to relax smooth muscles:   Terbutaline Hydrallazine  Episodes refractory to this initial management include direct irrigation of the corporeal bodies of the penis Dec 02, 2013 Dr Afzal Haq Asif 48
  49. 49. Dec 02, 2013 Dr Afzal Haq Asif 49
  50. 50. 8.Vaso-occlusive pain Crises: Summary  Most common symptoms of SCD  Severe pain  Caused by sickle-shaped red blood cells trapped in small blood vessels causing localized ischemia. Triggered by  Dehydration, fever, cold exposure, and emotional stress  Therapy  Intravenous/Oral hydration  Pain management  It is useful to assess pain in a standard manner using pain measurement scales ……………..See next Causal Treatment: (treatment of the cause)  Poloxamer 188 (Flocor) a surfactant returns RBCs to a non adhesive state and blocks RBC aggregation to enhance blood flow in ischemic areas Dec 02, 2013 Dr Afzal Haq Asif 50
  51. 51. Pain scale 0 – Pain free.  Mild Pain – Nagging, annoying, but doesn't really interfere with daily living activities.  1 – Pain is very mild, barely noticeable. Most of the time you don't think about it.  2 – Minor pain. Annoying and may have occasional stronger twinges.  3 – Pain is noticeable and distracting, however, you can get used to it and adapt.  Moderate– Interferes significantly with daily living activities.  4 – Moderate pain. If you are deeply involved in an activity, it can be ignored for a period of time, but is still distracting.  – Moderately strong pain. It can't be ignored for more than a few minutes, but with effort you still can manage to work or participate in some social activities.  6 – Moderately strong pain that interferes with normal daily activities. Difficulty concentrating. Dec 02, 2013 Dr Afzal Haq Asif 51
  52. 52. Pain Scale  Severe Pain – Disabling; unable to perform daily living activities.  7 – Severe pain that dominates your senses and significantly limits your ability to perform normal daily activities or maintain social relationships. Interferes with sleep.  8 – Intense pain. Physical activity is severely limited. Conversing requires great effort.  9-Excruciating pain. Unable to converse. Crying out and/or moaning uncontrollably.  10 – Unspeakable pain. Bedridden and possibly delirious. Very few people will ever experience this level of pain Dec 02, 2013 Dr Afzal Haq Asif 52
  53. 53. Pain Management Mild to moderate pain  NSAID’s or acetaminophen. Moderate pain  Weak opioid, such as codeine or hydrocodone. Severe pain  IV opioid morphine, hydro-morphone, fentanyl, and methadone.  Titrate to pain relief and then administer on a scheduled basis with as- needed dosing for breakthrough pain.  Patient-controlled analgesia can be used  Avoid  Meperidine should be avoided because accumulation of the normeperidine metabolite can cause neurotoxicity, especially in patients with impaired renal function  Minimize dependence /addiction by :  Aggressive pain control,  Frequent monitoring,  Tapering medication according to response Dec 02, 2013 Dr Afzal Haq Asif 53
  54. 54. Principles of pain management (WHO guidelines)  Morphine is the preferred agent in treatment of sickle cell pain.  Start by the mouth  By the Clock:  Regular analgesia (4-6 hourly) with breakthrough doses when needed  By the ladder:  Patients move up the ladder or may also move down the ladder if pain decreases.  Individualized Therapy:  Start with higher step for Patients presenting with moderate to severe pain.  Some don’t tolerate oral medication, plan for alternative route.  Consider non drug therapies. as well  No standard dose of opioid - morphine from 5mg to 1000mg every four hours.  With attention to detail:  Total analgesia usage should be monitored every 24 hours,  Breakthrough doses should be adjusted in line with changes to regular medication.  New pain should be assessed promptly  Patients should be informed of possible adverse drug effects. Dec 02, 2013 Dr Afzal Haq Asif 54
  55. 55. Dec 02, 2013 Dr Afzal Haq Asif 55
  56. 56. When and how IV REASSESS before starting IV opioids and ADJUST dose frequently, but not before 8 hours Scheduled IV Narcotic Dosing for 24 hours, round the clock Morphine sulfate: 0.1 mg/kg, every 3-4 hours. 5 - 10mg, IV scheduled Hydromorphone: 0.015 mg/kg, 0.75 - 2mg, IV scheduled every 3-4 hours. Monitor vital signs and pain level, using the pain scale, before and after every dose Dec 02, 2013 Dr Afzal Haq Asif 56
  57. 57. IV dosing: cares Doses should be based on level of tolerance to opioids. Most SCD patients have some opioid tolerance. Maximum analgesic effect within 10-15 minutes and will usually last 2-3 hours.  Consider around-the –clock (ATC) (patient may refuse) to ensure the patient is offered the medication consistently at the preferred interval. Dec 02, 2013 Dr Afzal Haq Asif 57
  58. 58. Scheduled IV Narcotic Dosing -- Opiate Tolerant patients Convert the patients usual oral dose to IV: Morphine IV/PO ratio: 1:3 Hydromorphone IV/PO ratio: 1:5  Example: Patient is taking morphine SR 60mg PO q12h and is now in pain crisis, requiring an additional 10mg PO q4 hours. 10mg X 6 = 60 mg + (60 mg x 2) = 180 mg PO morphine/day.  Convert PO to IV: 180mg PO / 3 = 60mg IV over 24h = 10mg IV q4h  Start with 50-75% of the calculated equianalgesic dose if changing / converting to a different opioid to allow for incomplete cross-tolerance between opioids. Dose adjustment for taper Decrease dose by 25% per day once the patient’s pain is under control for 24 hours Dec 02, 2013 Dr Afzal Haq Asif 58
  59. 59. Monitoring the patient Chest X-ray: Order for any patient with cardiopulmonary complaints, hypoxia, know chronic lung disease, fever, tachycardia, or tachypnea. Complete blood count q24 hours Comprehensive metabolic panel, magnesium, phosphorous q48 hours Keep magnesium level > 2 mg/dL:  Magnesium < 1.8 mg/dL, replace with IV magnesium  May need to follow with daily oral supplementation  Magnesium > 1.8 mg/dL, replace with oral product Lactic dehydrogenase (LDH) q72 hours Dec 02, 2013 Dr Afzal Haq Asif 59
  60. 60. PCA  Patient-controlled analgesia (PCA) is a method of pain control that gives patients the power to control their pain. In PCA, a computerized pump called the patient-controlled analgesia pump, which contains a syringe of pain medication as prescribed by a doctor, is connected directly to a patient's intravenous (IV) line. Dec 02, 2013 Dr Afzal Haq Asif 60
  61. 61. Patient Controlled Analgesia (PCA)  For setting where scheduled IV dosing is not controlling the patient’s pain.  There is no “PCA protocol.”  Continuous opioid infusion  should not be used in opioid naive patients until assessed the needs over a given period of time (i.e. after 12 hrs of demand/bolus doses)  Only use a in patients with a known opioid requirement.  Those patients taking daily opioids: calculate an equianalgesic dose of currently used opioids over past 24 hrs and then convert to an equianalgesic basal rate  Example: Patient taking 120 mg extended release morphine Q 12 hrs now in crisis taking an additional 15 mg immediate release morphine q 4 hrs. 15 mg X 6 = 90 mg + (120 mg X 2)= 330 mg PO morphine/day. Convert to IV equivalent 330/3= 110 mg IV morphine/24 hrs = 4-5 mg/hr.  If changing/converting to a different opioid, start with 50-75% of the calculated equianalgesic dose to allow for incomplete cross-tolerance between opioids. Afzal Haq Asif Dec 02, 2013 Dr 61
  62. 62. Titration of Dose Basal infusions will take at least 8 hours to reach steady state. Do not titrate the basal rate more frequently than every 8 hours. Never increase basal rate by more than 100% at any one time. Demand Doses: Adjust demand dose size every 30-60 minutes to quickly reach adequate analgesia.  For mild-moderate pain increase dose by 25-50%.  For moderate-severe pain increase dose by 50-100%. Dec 02, 2013 Dr Afzal Haq Asif 62
  63. 63. Converting IV to Oral Pain Management Once the IV dose has been tapered to 50% of the initial dose, start oral morphine or hydromorphone: Morphine & Hydromorphone: Add total daily dose of IV morphine received; multiply by 2-3 to determine total daily dose. Immediate release formulations should be administered on a scheduled basis, every 4 hours. Sustained release formulations should be administered every 12 hours. Morphine to oral Oxycodone: Convert morphine 10mg IV q4h to oxycodone 30 mg PO q6h. Dec 02, 2013 Dr Afzal Haq Asif 63
  64. 64. Adjunct therapies Bowel regimen: All patients on opioids must also be on a bowel regimen of stool softener and a cathartic. May administer Hydroxyzine 25-50 mg PO with each narcotic dose. Itching: Diphenhydramine 50mg IV/PO can be given with the initial dose of morphine and PRN Diphenhydramine may be given in conjunction with opiates for additive effect.  Nausea: administer prochlorperazine 10mg PO PRN nausea. Dec 02, 2013 Dr Afzal Haq Asif 64
  65. 65. Evaluation of Therapeutic outcomes All patients should be evaluated regularly to establish change in baseline, parameters Laboratory evaluations  complete blood cell and reticulocyte counts HbF level. Kidney and Liver function tests and pulmonary function Patients should be screened for retinopathy. The efficacy of hydroxyurea can be assessed by monitoring the number, severity, and duration of sickle cell crises. Dec 02, 2013 Dr Afzal Haq Asif 65
  66. 66. References and further reading Pharmacotherapy: pathophysiologic approach  302303  Vaso-occlusive disorders Future prospects: Stem cell therapy:  gene-therapy-for-246937.aspx For some references please visit: ref=hl Dec 02, 2013 Dr Afzal Haq Asif 66
  67. 67. Thank You Very Much Dec 02, 2013 Dr Afzal Haq Asif 67
  68. 68. Thank you very much Dec 02, 2013 Dr Afzal Haq Asif 68