SCD 2-9-2017 Final JJ & DH
2/13/2017Evidence-BasedManagement of UncomplicatedSickle Cell Disease Vaso-Occlusive CrisisJasmine Jones,Jones Pharm DD, BCGPDonna Hunter, MS, RN-BC, ACNS-NP, ANP-BCSickle Cell Case Study25 year old female, history of SCD and AVNbilateral hips. Presents to the ED reporting 10/10dull, aching pain in back and bilateral hips. Height5’5” weight 68kg. Labs – WBC 12,000,,, hgbg 7.3,, reticulocytey count383, scr 0.3, BP 112/73 Home pain regimen - morphine ER 90 mg BID,morphine IR 15 mg 1 tab q6h prn (using ATC forthe last 2 days)2Objectives Define sickle cell disease.Explore the prevalence of sickle cell in the U.S.Describe the pathology of sickle cell disease.Examine the clinical presentation andcomplications of sickle cell disease and vasoocclusive crisis (VOC). List evidence based treatment strategies for VOCpain management. Discuss an evidence-based treatment algorithmand order set for VOC.31
2/13/2017Sickle Cell Definition4DefinitionSickle cell disease is a group of inherited redblood cell disorders with an abnormality in theoxygen carrying protein of the hemoglobin.Autosomal recessive pattern.(50%) Sickle Cell Trait(25%) Sickle Cell Disease(25%) s.htmlDefinitionSickle cell trait (HbSA)Carrier, no expression of disease.4 common types of sickle cell (HbS) disorders with sickle cellanemia being the most common and most severe. (y , hemolytic)y )HbSS,, sickle cell anemia,, (normocytic,HbSC, (normocytic, hemolytic)HbS Beta 0-thalassemia, (microcytic, hemolytic)HbS Beta -thalassemia, (microcytic, hemolytic)Rare versions HbSD, HbSE, HbSO, severity varies.62
2/13/2017Sickle Cell Diagnosis7DiagnosisPrenatal screening Chorionic villus sampling, amniocentesis.Newborn screening Blood smear, red cell morphology.Red cell variation– Size (anisocytosis), shape (poikilocytosis), colorof red cells,, sickle shapep ((Elliptocytes).p y )– Howell-Jolly Bodies (small pieces of nuclearmaterial in RBC seen after hemolysis).SICKLEDEX Solubility test ( 6 months old).– 10% sickled cells present test is positive.Reprinted with permission from Ulrich Woermann, MD, University of Bern,Switzerland (www.hemosurf.ch), published by Medscape Drugs &Diseases (http://emedicine.medscape.com/), 2017, available erview.8DiagnosisHemoglobin electrophoresisConfirmatoryDifferentiates the type of hemoglobin disorder.NormalSickle cell diseaseSickle cell -3%2-3%HbF0.8-2%2%2%93
2/13/2017Sickle Cell Prevalence10PrevalenceAncestry Africa, Middle East, Mediterranean & South Asia.Sickle Cell Trait 1 in 13 African Americans.Sickle Cell Disease 100,000 Americans affected. 1 in 365 African Americans births. 1 out of every 16,300 Hispanic American births.11By Muntuwandi at English Wikipedia, CC BY-SA d 2932857PrevalenceRegistry and Surveillance System for Hemoglobinopathies (RuSH)124
2/13/2017PrevalenceCDC & National Institutes of Heath sponsored projects to improve care forthe population and to improve data collection.(RuSH)Registry and Surveillance System for Hemoglobinopathies CA, FLA, GA, Michigan, NY, NC & Pennsylvania.(PHRESH) Public Health Research, Epidemiology, and Surveillance forHemoglobinopathies. CA, GA & Mississippi.Sickle Cell Data Collection Program, (SCDC) CA & GA, study on long term trends in diagnosis, treatment and access for SCD.HP 2020, Sickle cell13PrevalenceHospital statistics 230, 000 ED visits for pain crisis per year. Acute care use is estimated at 1.5 billion annual. A higher risk of death with more than 3 hospitalizations in a year.Kennestone Regional Medical CenterJuly 2015 – Feb 2016 34 Patients admitted with sickle cell crisis. 17 Multiple admissions. 12 Readmissions less than 30 days. 5 Readmissions less than 1 week. Average 10 patients per month. Average 4 patients per month without readmits. Average LOS 5, highest LOS 23 & lowest LOS 1.14Pathology155
shcard/review/3668926PathologyLow oxygenation states cause cells toclump together and block blood flowin the capillaries causing pain due tolack of oxygen to the tissues.The cells become irreversibly sickledand have a short life span of 10-20days.Anemia occurs as bone marrowproduction can not keep up with thebreakdown.Sickling factors: Hypoxia, high altitude, flying innon-pressurized planes,dehydration, acidosis, /health-topics/topics/sca/Clinical Presentation17186
2/13/2017Clinical PresentationAnemia: chronic, hemolytic, shortness ofbreath, tired, dizzy, & pale.Spleen: function is weakened or destroyedearly in life.Eyes: retina damage common.Heart disease: enlarged heart, pulmonaryyp, shortness of breath and fatigue.ghypertension,Kidneys: trouble concentrating urine,hematuria, infarcts.Liver & Gall bladder: jaundiced, intrahepaticcholestasis, gall stones common.19Clinicopathologic findings in sickle cell anemia. The findings are a consequence of infarctions, anemia,hemolysis, and recurrent infection. From Damjanov, 2000. Found on the free dictionary sightClinical PresentationLeg ulcers: chronic, painful.Joints: avascular or aseptic necrosis. Bones inhips, knees, ankles, & shoulders affected.Priapism: prolonged painful erections.Acute chest syndrome: serious, acute, 2ndmost common reason for hospitalization & mostcommon cause of death. Symptoms, SOB,chest pain, fever, cough & tachypnea.Stroke: silent brain injury versus clinical stroke.One of the most common devastatingcomplications.20Clinicopathologic findings in sickle cell anemia. The findings are a consequence of infarctions, anemia,hemolysis, and recurrent infection. From Damjanov, 2000. Found on the free dictionary sightClinical PresentationPsychosocialLife long illness with many interactions with health care providers.Poor self image, negative thoughts and feelings about the condition,stigmatization, cognitive impairments, fears, anxieties, anger, &depression.Potential for substance abuse and addiction/alcohol abuse, but nomore than any other chronic diseasedisease.Concerns regarding, tolerance, dependence, and addiction addcomplexity to patient care.Patients report fear of not being believed about their pain, being labeleda “drug seeker” or receiving inadequate pain control when presentingwith crisis and this creates more stress/anxiety for the patient.217
2/13/2017Clinical PresentationPsychosocialHigh tolerance and physical dependence from long term opioid usecombined with the provider’s fear of over-sedation can lead to undertreatment, which can create what's called a pseudo-addiction.pdo not equalqaddiction.Tolerance and dependenceSickle cell disease has the same rate of addition as any chronicdisease.22Clinical PresentationPsychosocialStudies showPatients were 25 times more likely to report clinicians did a good jobwith pain management when they perceived the ED physician and sitetreated them with trust and respect.85% of physician’s reported they followed opioid retreatmentguidelines. High volume providers & those with negative attitudes wereless likely to retreat in 30 minutes.Multidisciplinary pain team: medical, nursing, social services,pharmacology, & psychology.23Clinical PresentationVaso-occlusive or pain crisisPain resulting from tissue ischemia due to vaso-occlusion. Most commonclinical picture in adults. Episode may last for hours, days, or weeks. Complex pain, acute on chronic, treat as acute.– Nocioceptive hallmark, neuropathic or mixed. Pain can occur anywhere and in several places at same time.– Most common: Lower back, legs, arms, abdomen, & chest.– Sharp, stabbing, throbbing, intense. Pain varies from person to person, episode to episode. Pain management plans for home and hospital treatment helpful.248
2/13/2017Clinical PresentationEmergent or urgent careNeed to rule out complications. Fever greater than 101 F, shortness of breath.Chest painAbdominal swellingSevere headache, sudden loss of feeling, weakness, or movement.SeizureSudden vision problem.Painful erection lasting longer than 4 hrs.Acute pain anywhere not controlled by home medications.25Clinical PresentationDiagnostic tests CBC with retic countBMPLiver function testBun, creatinine & serum electrolytesRadiologyEcho & heart cath if cardiac symptomsAdults annual routine labs: retic, % Hb, renal function, hepatobiliaryfunction, pulmonary function26Scanning electron micrograph showing a mixture of red blood cells, some with round normal morphology, some with mild sickling showingelongation and bending By NIDDK - (US government agency) site at http://www.cc.nih.gov/ccc/ccnews/nov99/ . The photo is attributed toDrs. Noguchi, Rodgers, and Schechter of NIDDK., Public Domain, https://commons.wikimedia.org/w/index.php?curid 630192Evidence Based Treatment279
2/13/2017Evidence Based TreatmentTreat the symptoms Oxygen therapyPain relieving medicationsAntibioticsIV fluidsHydroxyurea (HU), FDA approved in 1998 in adults with sickle cellanemia (SCA). Induces formation of HbF. Blood transfusions, used for severe cases, iron overload possiblewith probable heart,heart & liver failurefailure. Erythrocytapheresis, removes HbS and replaces with packed cells.Cure: Hematopoietic stem cell transplantation or allogenic bone marrowtransplant.28Evidence Based TreatmentTreat the symptoms Medical marijuana– California study on Inhaled (4.7% THC/5.1% CBD) vs placebo.ClinicalTrials.gov Identifier: NCT01771731.– Medical marijuana site, 16 states with laws on ce.php?resourceID 000881 New research:– St. Jude Children’s Research Hospital. Found a way to Increasefetal hemoglobin with the use of the CRISPR gene editing toremove a section of DNA that stimulates “gamma-to-beta”switching.29PAIN THERAPY: OPIOIDADVERSE EFFECTS3010
2/13/2017Constipation Develops due to the actions of opioids onreceptors throughout the GI tract– Decrease in bowel motility and peristalsis– Increased anal sphincter tone The best prevention is a scheduled laxativeregimen First line laxatives have stimulant activity– Senna (Senokot) tablets– Bisacodyl (Dulcolax) tablets– Senna/Docusate (Peri-Colace, SennaS, Senna-Plus)Goodheart CR, Leavitt SB. Managing Opioid-Induced Constipation in Ambulatory-Care Patients.August 2006. Available online at www.Pain-Topix.com.Nausea and Vomiting Develops due to the actions of opioids inthe chemo trigger zone (CTZ) Phenothiazines– Compazine 5 – 10 mg PO TID-QID, 25 mg PR BID;Promethazine 12.5 – 25 mg PO/PR/IV/IM Q4-6H PRN Serotonin receptor antagonist– Ondansetron 4 – 8 mg PO/IV Q8H PRN Dopamine antagonist– Metoclopramide 5 – 10 mg PO/IV Q6H PRN32Pruritus Mechanism is cutaneous mast cell andbasophil activation which leads tohistamine release Antihistamines– Diphenhydramine 25 – 50 mg PO Q6H PRN– Hydroxyzine 25 mg PO Q6H PRN Opioid receptor mixed agonist-antagonist– Nalbuphine 2.5 – 5 mg IV33Januzzi R. Nalbuphine for treatment of opioid-induced pruritis: a systematic review ofliterature.ClinJPain.Jan2016;32(1):87-93.11
2/13/2017Sedation Patient factors that increase risk– Sleep disordered breathing, i.e. OSA– Obesity– Chronic lungg disease– Opioid naïve– PCA demand continuous rate infusion– Advanced age– Renal dysfunction (dialysis or CrCl 30ml/min)34Pasero Opioid-induced SedationScale (POSS)35Pasero C. Assessment of sedation during opioid administration for painmanagement.JPeriAnNurs.June 2009:24(3);186-90PAIN THERAPY: OPIOIDPHARMACOLOGY3612
2/13/2017Pain PathwaysPain PathwaysSubstance PGlutamateNMDANorepinephrineS t iSerotoninGABAEndorphinsAscending (excitatory)Descending (inhibitory)Purves et al, Neuroscience 2nd. Edition, 2001Opioid Mechanism of Action Interact with opioid receptors (mu, kappa, delta) mu receptor is the primary site of action Methadone– Blocks NMDA receptor– Enhances serotonin and norepinephrine activity Tramadol (Ultram , Ultracet )– Enhances serotonin and norepinephrine activity Tapentadol (Nucynta , Nucynta ER )– Enhances norepinephrine activityOpioid Chemical Classes– Phenanthrenes Codeine (Tylenol #3)Morphine (MS Contin, Roxanol)Hydrocodone (Vicodin, Lortab, Norco)Hydromorphone (Dilaudid)Oxycodone (OxyCONTIN, Percocet)Oxymorphone (Opana)Buprenorphine (Suboxone, Butrans)– Diphenylheptanes– Methadonee ado e Propoxyphene (removed from the US market)– Phenylpiperidines– Fentanyl (Duragesic) Meperidine (Demerol) Benzmorphans Pentazocine (Talwin)– Miscellaneous Tapentadol (Nucynta) Tramadol (Ultram)Trescot, et al. Pain Physician, 2008;SI11:S133-S15313
2/13/2017Opioid Chemical Content/LQCL1301/ assoc/CL 13-01.htmlTrue Opioid Allergic Reactions Mediated by immunoglobulin E (IgE) Symptoms - hives, maculopapular rash,erythema multiforme, pustular rash,severe hypotension, bronchospasm,angioedema, “anaphylaxis-type reactions” An opioid from a different opioid classmust be used if opioid therapy isnecessary41PseudoallergicOpioid Reactions Non-IgE mediated, mechanism is cutaneousmast cell and basophil activation which leads tohistamine release Symptoms - flushing, sneezing, sweating,exacerbation of asthma, low blood pressure,nausea, vomiting, constipation or somnolence,pruritus and rash These adverse effects DO NOT preclude useof morphine.4214
2/13/2017Opioid AgonistsPhenanthrenes Codeine Tylenol #3 Morphine MS Contin , Roxanol Hydrocodone Vicodin , Lortab , Norco Hydromorphone Dilaudid Oxycodone OxyCONTIN , Percocet Oxymorphone Opana Diphenylheptanes Methadone Propoxyphene Darvon , Darvocet (removed from the US market)Phenylpiperidines Fentanyl Sublimaze , Duragesic Meperidine Demerol Not recommended for painOpioid Partial & Mixed AgonistsPartial AgonistsPhenanthrenes Buprenorphine (Butrans )Miscellaneousp((Nucynta )y) Tapentadol Tramadol (Ultram )Mixed AgonistAntagonistsPheneanthrenes Buprenorphine Naloxone(Suboxone ) Nalbuphine (Nubain ) Butrophanol LevorphanolBenzmorphans Pentazocine /Naloxone(Talwin , TalwinNx )Opioid Pharmacokinetics Absorption– Hydrophillic opioids absorbed in GI tract Morphine, hydrocodone, hydroMORPHONE,oxycodone– Lipophillic opioids absorbed in gi tract,sublingual transbucalsublingual,transbucal, transdermal Fentanyl, methadone Distribution– Hydrophillic opioids remain in blood– Lipophillic opioids may distribute into fat tissues Methadone extensively distributed into the tissues15
m/curriculum c03.htmOpioid Pharmacokinetics Metabolism via the liver– Active drug metabolites: provide analgesia, maycause negative side effects– Inactive drug metabolites: no clinical effects– CYP 450 inhibitors/inducers pose risk for druginteractions Inhibitors – slow down metabolism Inducers – speed up metabolism Elimination via the kidneys– Decreased kidney elimination of active drugmetabolites may lead to toxicityOpioids and Renal Dysfunction Majority of opioid analgesics metabolize to activemetabolites that are eliminated via the kidneys– Exceptions: methadone and fentanyl Renal dysfunction leads to accumulation of bothparent compoundpand active/inactivethe pmetabolites Prolonged exposure to active metabolites greatlyincreases risk for respiratory depression,hypotension, or CNS toxicity These ADEs ARE PREVENTABLE4816
2/13/2017Opioid Metabolism odonexxUse with caution in moderate to severekidney impairmentMorphinexxNot recommended in severe kidneyimpairment (CKD Stage 4,5 or CrCl 30 ml/min)OxycodonexHydromorphonexDrugCYP 450MetabolismxCommentsSafer in kidney impairment (activemetabolite has weak clinical effects)Use with caution in moderate to severekidney impairmentxFentanylxxSafer in kidney impairmentMonitor for CYP450 drug interactionsMethadonexxSafer in kidney impairmentCaution in severe liver impairmentPotential for serious CYP 450 druginteractions leading to respiratorydepression or heart arrhythmiasSmith H. Opioid Metabolism. Mayo clinic proceedings. 2009;84(7):613-624Opioid Pharmacodynamic ComparisonDrugEliminationHalf-life(hrs)Duration ofAction (hrs)DosingIntervals(hrs)Peak (min)Oxycodone IR (PO)Oxycodone CR (PO)2-33-68-122-61260 – 9090 - 180Morphine (IV)Morphine IR (PO)Morphine CR (PO)2-32-33-43-68-122–42–68 - 1215 – 3060 – 9090 - 180Hydromorphone (IV)Hydromorphone IR(PO)2-32-33-43-62–42–610 – 2030 - 90Fentanyl (IV)Fentanyl (TD)3–417 (afterremoval)248-72, up to 12 afterremoval2-37215 – 3024Methadone (PO)12-150 hrs3-6, initially, and 8 –12 (or longer) withrepeatedadministration4 – 6 (initial)8 – 24 (repeatedadministration)150IR immediate releaseCR controlled releasePO oralIV – intravenousTD transdermalAdapted from UpToDate 2015:Selected opioid analgesics for pain and equianalgesic ey ONC/58864&source graphics search&rank 0&search opioidsPasero C and McCaffery M.“Pain Assessment and Pharmacologic Management”Chapter 16:Initiating Opioid Therapy,Section IV, Opioid Analgesics. Table 16-1: Equianalgesic Dose ChartOpioid Pharmacodynamic ComparisonDrugEliminationHalf-life(hrs)Duration ofAction (hrs)DosingIntervals(hrs)Peak (min)Oxycodone IR (PO)Oxycodone CR (PO)2-33-68-122-61260 – 9090 - 180Morphine (IV)Morphine IR (PO)Morphine CR (PO)2-32-33-43-68-122–42–68 - 1215 – 3060 – 9090 - 180Hydromorphone (IV)Hydromorphone IR(PO)2-32-33-43-62–42–610 – 2030 - 90Fentanyl (IV)Fentanyl (TD)3–417 (afterremoval)248-72, up to 12 afterremoval2-37215 – 3024Methadone (PO)12-150 hrs3-6, initially, and 8 –12 (or longer) withrepeatedadministration4 – 6 (initial)8 – 24 (repeatedadministration)150IR immediate releaseCR controlled releasePO oralIV – intravenousTD transdermalAdapted from UpToDate 2015:Selected opioid analgesics for pain and equianalgesic ey ONC/58864&source graphics search&rank 0&search opioidsPasero C and McCaffery M.“Pain Assessment and Pharmacologic Management”Chapter 16:Initiating Opioid Therapy,Section IV, Opioid Analgesics. Table 16-1: Equianalgesic Dose Chart17
2/13/2017PAIN THERAPY: MORPHINEDOSING STRATEGIES FORSICKLE CELL PAIN CRISIS52Morphine Initiate loading doses every 15-30 min untilpain is decreased by 30-50% Followed by scheduled (ATC)maintenance IV opioid regimen– IV PCA or IV bolus doses Q3H ATC Continue long-acting oral opioid– IV PCA opioid continuous infusion may not berequired if long-acting oral is reordered53U.S. Department of Health and Human Services.National Institutes of Health, NationalHeart, Lung, Blood Institute. Evidence-based management of sickle cell disease. ExpertPanel Report, 2014.Minimal Effective Analgesic Concentrationand the Analgesic CorridorSEDATIONCONVENTIONALPRN DOSINGANALGGESIAMEACPAINOPIOID CONCENNTRATIONPCADOSING6AM8AM10 AM12 PM2 PMAnesth Analg 2005;101:S44–S6118
2/13/2017Calculating Loading DosesWeight based dosing(opioid naïve and/or 50kg) Calculate the initial IV morphine loadingdose at 0.1-0.15mg/kg (max 10mg)55American Pain Society.Principles of analgesic use in the treatment of acute pain and cancerpain.6th edition.2008Calculating Loading DosesIndividualized dosing (opioid tolerant) Find the morphine equivalent daily dose(MEDD) - convert the current 24 hour ORALopioid dose to IV morphine Reduce by 30% if converting betweenopioids (incomplete cross-sensitivity) Order 10% of the calculated equianalgesicdose as the loading dose Morphine IV usual dose 5-10 mg56American Pain Society.Principles of analgesic use in the treatment of acute pain and cancerpain.6th edition.2008Equianalgesic Chart57American Pain Society Sickle Cell Guidelines19
2/13/2017Initial PCA Demand Doses58American Pain Society.Principles of analgesic use in the treatment of acute pain and cancerpain.
Sickle cell trait (HbSA) Carrier, no expression of disease. 4 common types of sickle cell (HbS) disorders with sickle cell anemia being the most common and most severe. HbSS, sickle cell anemia,,( y, y) (normocytic, hemolytic) HbSC, (normocytic, hemolytic) HbS Beta 0-thalassemia, (microcytic, hemolytic)
of SCD were documented. Comparison was made with non-SCD population as well as within 3 different age groups ( 5, 5-17 and 18 years) within the SCD population. Results: From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in age group 5-17 years.
Despite universal newborn screening for SCD in the United States, one study found that long-term follow-up after diagnosis was not performed in nearly one-third (30.8%) of cases.3 SCD is also associated with high treatment costs. For an average person with SCD reaching age 45, total lifetime health care costs
The Sickle Cell Disease (SCD) Pre-Infusion Data Form (Form 2030) is one of the Comprehensive Report Forms. This form captures SCD-specific pre-infusion data such as: disease classification at diagnosis, transfusion status prior to the start of the preparative regimen, organ assessments prior to the start of the preparative
service at time of appointment, all 4 SCDs are the same as the calendar date on which the employee is appointed. Actual A rehired employee who has prior creditable and/or military service will have a recomputed SCD referred to as a constructed SCD Constructed Actual and Constructed SCDs To c
popularized the SCD in her book, Breaking the Vicious Cycle: Intestinal Health Through Diet. The SCD can be well balanced, but is very specific in the types of sugars and starches that are allowed (Table 1). The natural SCD aims to permit single sugars, or monosaccharides, such as those found in some fruits, certain vegetables, and
SCD is 1 in 360 live births among African Americans and 1 in 16,300 live births among Hispanics.4 In New York, the estimated incidence is 1 in 230 newborns born to non-Hispanic black mothers and 1 in 2,320 newborns born to Hispanic mothers.5 People with SCD are at risk of life-threatening complications and organ damage, reducing
Modified SCD and FODMAP Diets Combination The Specific Carbohydrate Diet (SCD) is intended mainly for irritable bowel syndrome, Crohn's disease, . The foods allowed on the Specific Carbohydrate Diet are based on the molecular structure of the foods. The allowed carbohydrates are monosaccharides and have a single molecule structure that .
The SCD-4 has been designed to quickly wash, drain and dry, up to four (10" diameter x 30" length) cylinders in less than 2 minutes. The SCD-4 utilizes compressed air and hot water to drain and flash dry compressed gas cylinders, after hydrostatic testing. A Control Box contains individual controls to provide a range of times for each process.
