Transcript Sickle Cell Emergency 2

Acute Complications of
Sickle Cell Disease &
Management Guidelines
Emily Riehm Meier, M.D., M.S.H.S.
September 28,2016
317.871.0000 or 877.256.8837
Objectives
1. Describe the most common complications of
sickle cell disease, including acute chest
syndrome, vaso-occlusive pain crisis, and stroke.
2. Recognize a patient with sickle cell disease who
needs emergency care.
3. Develop a management plan for a patient with
sickle cell disease who presents for an acute care
visit.
The Red Cell
• Each red cell has 200- 300
• million hemoglobin
molecules
• Four globin chains per
• hemoglobin molecule:
• 2 α chains
• 2 β chains
• One heme moiety
• within each globin chain
• to bind oxygen
Pathophysiology 1 : Polymer Formation
• HbS is an abnormal β globin protein caused by a single
amino acid substitution (Glu -> Val)
• Polymerizes upon deoxygenation
• HbS polymers pull cell into sickle shape
• Other known triggers of polymerization: dehydration, cold
temperatures.
O2
O2
O2
O2
HbA
HbS
Pathophysiology 2: Vaso-Occlusion
• Normal red blood cells are flexible enough for
passage through microcirculation.
• Sickle cells are rigid and become stuck in the capillaries.
• Tissue is deprived of oxygen.
• Over time organ damage occurs (i.e. spleen, retina)
Pathophysiology 3: Nitric Oxide Depletion
Hemolysis, endothelial dysfunction
Viscosity, vaso-occlusion
Pathophysiology 4: Inflammation
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Interplay of white cells and platelets
Reperfusion injury
Upregulation of cytokines
Thrombosis
Clinical Manifestations of Sickle Cell Disease
 Unpredictable severe pain
• Tissue damage from lack of blood flow
 Anemia
 Damage to many organs:
• Kidney, spleen, brain, lung, retina, bone
 Unpredictable hospitalizations & absences
Leg ulcers
Retinopathy
Stroke
SCD Manifestations
Splenic Sequestration
Pain-Dactylitis
AVN
Acute Chest Syndrome
Survival of Children with Sickle Cell Disease
Quinn CT, et al. Blood 2010;115:3447-3452
State Distribution of Hemoglobinopathies
Over 50 cases
31-50 cases
16-30 cases
6-15 cases
1-5 cases
State Distribution of Hemoglobinopathies
Over 50 cases
31-50 cases
16-30 cases
6-15 cases
1-5 cases
Emergencies in Sickle Cell Disease
 Fever of 101oF or higher (100.4oF in young infants)
 Acute Chest Syndrome: Respiratory symptoms/chest
pain with abnormal chest Xray
 Stroke: Neurologic symptoms/deficits
 Priapism: Prolonged penile erection
 Splenic sequestration: Pallor, lethargy, hypotension,
with increased size of the spleen
 Pain not responding to home pain control regimen
Sickle Cell Interim History and ROS:
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Sickle genotype
Baseline hemoglobin
Acute chest syndrome –PICU care needed
Stroke –recent TCD results
Spleen complications – Sequestration, splenectomy
History of Pneumococcal bacteremia, meningitis
Priapism
Transfusions – transfusion problems e.g. alloAntibodies
Hydroxyurea and adherence
Immunizations – esp Pneumovax, Prevnar 13, Flu
Sickle Cell Emergency 1: Fever > 101⁰F
 Parents counseled to seek advice for all temperatures
>38⁰C/100.4⁰F in infants and >101⁰F in older child
 Prompt assessment at PCP/ Heme office/ED for source of fever
AND
Empiric antibiotics even if source found or not
 Admit infants <1 year
 In children > 1 year, Ensure child will have outpatient follow up
AND
2nd dose Ceftriaxone if necessary
Infection Risk and SCD
1. Functional or Surgical Asplenia
• Impaired clearance of IgG coated bacteria that are resistant
to opsonization
• Need an increased rate of opsonization to overcome
infection risk
• Delayed/decreased response to vaccines because of
impaired production of IgM
2. Decreased Opsonization
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Children with SCD have decreased rate of opsonization
compared to healthy children
Rubin and Schaffner, N Eng J Med 2014;371:349-356
Bjornson, Gaston & Zellner, J Pediatr 1977;91:371-378
Invasive Pneumococcal Disease and SCD
 Rate of IPD has declined since Prevnar
• Rate of IPD 13.5/100 patient years in 1980s
• 0.5-1/100 patient years in 2010
 IPD still happens in children with Sickle Cell
• Less than optimal adherence to Penicillin prophylaxis
• Non-vaccine serotypes
• Suboptimal vaccine response
Rubin and Schaffner, N Eng J Med 2014;371:349-356
Obaro and Iroh Tam, Pediatr Blood Cancer 2016;63:781-785
Management of Fever in an Asplenic Patient
Fever >101
Access to Medical Facility within 2 hours?
Yes
No
CBC/Retic
Aerobic Blood Culture
+ Chest Xray
Physical Exam
Take po antibiotics and immediately
begin travelling to medical facility
Ill appearing or abnormal labs or age <1 year?
Yes
Ceftriaxone im/iv
Admit to hospital
Broaden coverage
based on clinical presentation
No
Ceftriaxone im/iv
Discharge home provided
that followup is arranged and
reliable contact phone number available
SCD Empiric Antibiotics, Fever > 101⁰F
 Ceftriaxone – 1st line for most fever
• Active against S. pneumonia, H. influenzae, N.
meningitidis, community-acquired gram negative
 Clindamycin – if allergic to ceftriaxone
 Vancomycin – add if sepsis is likely
 Azithromycin – add for Acute Chest Syndrome
Sickle Cell Emergency 2: Acute Chest Syndrome
 Infiltrate on Chest Xray
and > 1 of the any of the
following:
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Fever
Cough
Chest Pain
Hypoxia
Wheezing
Tachypnea
 Leading Cause of Death in
SCD patients
Wang et al. Lancet 2011; 377:1663-1672
Khoury et al. Hemoglobin 2011; 35:625-635
Acute Chest Syndrome
 Classically develops 2-3 days after admission for pain crisis and
characterized by rapid (<12 hours) development of respiratory
symptoms and decompensation
 Causes:
• Fat emboli (from bone that is infarcted from red cell sickling)
• Infection
Gram positive cocci
Atypical organisms (mycoplasma most common)
• Lung infarction
• Cause only identified in 38% of patients
DeBaun MR, Struck RC. Lancet 2016;387:2545-2553
Desai PC, Ataga KI. Expert Opin Pharmacother 2013;14:991-999
Acute Chest Syndrome
 Much more commonly a subacute process that mimics:
• Bacterial pneumonia
• Bronchiolitis
• Asthma exacerbation
 Children much more likely to present with cough and fever
• 40% will have a normal physical exam, so high index of suspicion is
necessary
 Adults more likely to present with chest pain, dyspnea, and
multilobar involvement on chest Xray
DeBaun MR, Struck RC. Lancet 2016;387:2545-2553
Treatment for Acute Chest Syndrome
 Broad spectrum antibiotics
• IV Ceftriaxone (for S. pneumoniae)
• PO Macrolide (for C. pneumoniae or M. pneumoniae)
 Adequate analgesia (but not over-sedation)
 Adequate hydration (to prevent subsequent sickling but also
need to avoid fluid overload)
 Physical therapy
 Inhaled beta-agonists and corticosteroids
 Incentive spirometry
 Blood transfusion, exchange transfusion
 Oxygen, BiPAP, mechanical ventilation
DeBaun MR, Struck RC. Lancet 2016;387:2545-2553
Desai PC, Ataga KI. Expert Opin Pharmacother 2013;14:991-999
Sickle Cell Emergency 3: Stroke
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ISCHEMIC - blockage of blood flow to part of brain
o vascular stenosis
o microvascular sickling & thrombosis?
• Symptoms include
o motor or sensory deficit, >24hr (caveat: painless
limp)
• MRI / MRA / dWI
Strokes
• HEMORRHAGIC
bleed, e.g. aneurysm
• hypertension, increased ICP
• “worst headache of my life”
Non-contrast CT
Treatment – Neurosurgical
Prevention – control hypertension
Stroke Risk in Children with SCD
Adams RJ. Arch Neurol 2007;64:1567-1574
Age Distribution of Stroke by Age
Ohene-Frempong K, et al. Blood 1998;91:288-294
Exchange Transfusion vs. Simple Transfusion at
Time of Presentation
Exchange Transfusion at Presentation
Simple Transfusion at Presentation
Hulbert ML, et al. J Pediatr 2006;149:710-712
Exchange Transfusion vs. Simple Transfusion at
Time of Presentation
Exchange Transfusion at Presentatio
Patients who received a simple transfusion at the time
of presentation were 5 times more likely to have a
recurrent stroke in the future
(RR=5.0; 95%CI 1.3-18.6)
Simple Transfusion at Presentatio
Hulbert ML, et al. J Pediatr 2006;149:710-712
Sickle Cell Emergency 4: Priapism
• Prolonged, unwanted, painful erection of the penis
• Onset between 5 and 35 years of age
• Affects over 1/3 of males with SCD
• Often recurrent
• Stuttering Priapism: multiple, self-limited, lasts < 4 hours
• Onset is often in the early morning, waking the patient
Olujohungbe AB et al. J Androl 2011;32:375-382
Priapism – Treatment and Prevention
 Treatment includes:
• Pain relief, hydration
• Urination
• Intercavernosal injection of alpha adrenergic agent
(etilefrine or pseudoephedrine)
• Surgical shunt procedures
 Prevention with:
• Alpha adrenergic agents (etilefrine or pseudoephedrine)
• Hydroxyurea
• Possibly sildenafil
Broderick GA. J Sex Med 2012;9:88-103
Montague DK, et al. J Urol 2003;170:1318-1324
Burnett AL, et al. Am J Hematol 2014;127:664-668
Sickle Cell Emergency 5: Splenic Sequestration
• Most common from 6 mos-3 yrs of age in children
with HbSS
• Can occur into adulthood in people with HbSC or
HbSβ+thalassemia
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Drop in Hemoglobin by at least 2 g/dL
Rapidly enlarging spleen
Reticulocytosis (above baseline)
Mild to moderate thrombocytopenia
May be associated with fever, pain, tachycardia and
respiratory symptoms.
Emond AM, et al. J Pediatr 1985;107:201-206
Squiers JJ, et al. J Inv Med High Impact Case Rep 2016;1:1-3
Spleen Palpation Increases Incidence but
Decreases Mortality
Pre-Spleen Palpation Education
Year
No. of
attacks
Fatalities
Child years of
observation
1974
2
0
39
1975
7
2
74
1976
9
3
102
1977
7
2
130
1978
9
3
149
Incidence rate:
4.6 per 100 patient years of observation
Mortality rate:
29.4 per 100 events
Emond AM, et al. J Pediatr 1985;107:201-206
Spleen Palpation Increases Incidence but
Decreases Mortality
Pre-Spleen Palpation Education
Post-Spleen Palpation Education
Year
No. of
attacks
Fatalities
Child years of
observation
Year
No. of
attacks
Fatalities
Child years of
observation
1974
2
0
39
1979
18
0
182
1975
7
2
74
1980
20
1
209
1976
9
3
102
1981
22
2
241
1977
7
2
130
1982
22
0
245
1978
9
3
149
1983
16
0
236
Incidence rate:
4.6 per 100 patient years of observation
Incidence rate:
11.3 per 100 patient years of observation
Mortality rate:
29.4 per 100 events
Mortality rate:
3.1 per 100 events
Emond AM, et al. J Pediatr 1985;107:201-206
Treatments of Splenic Sequestration
 Intravenous fluids
 Blood transfusion – typically 5 mL/kg pRBC aliquots
 Splenectomy – usually reserved for recurrent splenic
sequestration
•
Review spleen
palpation and
signs/symptoms of
worsening anemia with
family members at
each clinic visit
Rhodes MM, et al. J Clin Gastroenterol 2014;48:99-105.
Sickle Cell Emergency 6: Vaso-Occlusive Episode
 The most common symptom of SCD
 May start as early as first year of life.
 Recurs unpredictably through the life
 Frequency and severity of pain is variable among
the patients
 Presents unique challenges for patients, families
and health professionals
Platt OS et al. New Eng J Med,1991;325: 11-16
Impact of Pain in Sickle Cell Disease
 Quality of life of patients and their caregivers
 Financial burden:
• Direct cost : Admissions and treatment of VOC
»over 75,000 hospitalizations
»over $475 million in 2004
• Indirect cost : Lost productivity, missed work or
school days
Steiner and Miller. 2004. hcup-us.ahrq.gov
African Tribal Names for Sickle Cell
o Chwechweechwe (relentless perpetual chewing)
o Adep (beaten up)
o HemKom (body biting)
Pain in SCD Starts Early
Dactylitis:
 Painful swelling of hand
and feet. Infarction of
bone marrow due to
occlusion of blood supply
 Presents as early as 6
months of age as fetal
hemoglobin starts to
decline
Acute Vaso-Occlusive Pain Crisis
 The characteristic
manifestation after early
childhood
 Precipitated by temperature
changes, stress, infection,
dehydration and unknown
factors
 Spine, pelvis, long and flat
bones are commonly
involved
39%: no episodes of severe pain; 1% had >6 episodes per year;
5% of SCD individuals accounted for >30% of episodes
Platt
r denotes the number of episodes of pain per patient-year, SS sickle cell anemia, SC hemoglobin SC disease, Sβ+
et al NEJM 1991; 325(1)11-6
sickleβ+-thalassemia, and Sβ0 sickle β0-thalassemia.
Frequent Hospitalization for Pain is a Risk Factor for
Early Mortality in SCD
Darbari DS et al. PLoS One. 2013;8:e79923.
Vaso-Occlusive Crises vs. Daily Pain
Smith WR et al. Ann Intern Med 2008;148:94-101
Episodes of Daily Pain
Smith WR et al. Ann Intern Med 2008;148:94-101
Episodes of Daily Pain
Smith WR et al. Ann Intern Med 2008;148:94-101
Episodes of Daily Pain
> 50% of patients experienced pain on >50% of the days;
30% experienced pain > 95% of the days
Smith WR et al. Ann Intern Med 2008;148:94-101
Pain in Sickle Cell Disease
 Sickle cell pain:
»Acute, severe and disabling (crisis)
»Chronic pain of variable degrees
» Rx: Ambulatory/ ED/ hospitalization
 Frequency of pain vary among SCD individuals for
both severe and mild/ moderate ambulatory pain
Outpatient Management of Pain
 Adequate hydration
 Avoid temperature extremes
 Anti-inflammatory (ibuprofen) alternating with oral
opioid
 Adequate rest
 Non-pharmacologic techniques
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Distraction
Deep Breathing
Guided Imagery
Acupuncture
Massage
Cognitive Behavioral Therapy
Yoga
Prayer
Inpatient Management of Pain
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IV fluids
IV opioids
Anti-inflammatories
Non-pharmacologic techniques
• Deep breathing exercises to prevent pneumonia
• Physical Therapy
 Therapeutic exercises
 Heat packs/whirlpool
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Distraction
Guided Imagery
Acupuncture
Massage
Cognitive Behavioral Therapy
Prayer
Summary
 Pain is the hallmark of sickle cell disease
 Acute chest syndrome is the leading cause of death in
people with sickle cell disease
 Patients who present with acute, overt stroke should be
treated with exchange transfusion to decrease risk of
recurrent stroke.
 Gold standard of therapy for priapism is intercavernosal
irrigation and injection of alpha adrenergic agonist.
 Splenic sequestration should be managed with iv fluids
and pRBC transfusion.
Thank you!
Questions?
[email protected]
Challenges of Chronic Pain Management
 No long term (>1 year) studies of opioid effectiveness for
chronic pain
 Mixed results with short term courses of opioid medications for
chronic pain
 In 2014, 10 million Americans reported using a prescription
opioid for a nonmedical reason
 Nearly 2 million Americans over age 12 years met diagnostic
criteria for substance use disorder involving prescription
opioids
 More than 165,000 deaths due to overdose of opioid pain
medication in US from 1999-2014
Dowell D, et al. JAMA 2016;315:1624-45
Olsen Y. JAMA 2016; 315:1577-1578
CDC Recommendations for Chronic Pain
Management
1. Nonpharmacologic therapy and nonopioid pharmacologic therapy
are preferred for chronic pain
2. Establish treatment goals before initiating opioid therapy
3. Discuss risks and realistic benefits of opioid use with patient
4. Choose immediate-release over extended release or long acting
opioids
5. Prescribe the lowest effective dose
6. Reassess risk/benefit ratio within 1-4 weeks of initiation
7. Continue to reassess risk factors for opioid related harms
8. Utilize state prescription drug monitoring programs
9. Consistent use of urine drug monitoring program
10. Do not prescribe opioids and benzodiazepenes concurrently
Dowell D, et al. JAMA 2016;315:1624-45
If Opioids are not the best option for chronic
pain, then
What Are Other Therapeutic Options to Improve
Chronic Pain in Patients with Sickle Cell Disease?
Vitamin D and Pain in Patients with SCD
Osunkwo, et al. Br J Haematol 2012;159:211-215
Other Micronutrients May Be Important
Martyres, et al. Ped Blood Cancer 2016;63:1060-1064
Other Micronutrients May Be Important
Martyres, et al. Ped Blood Cancer 2016;63:1060-1064
Complementary Medicine Approaches - Patients
Thompson and Eriator, Pain Med 2014;241-246
Complementary Approaches - Provider Perspective
 Providers willing to try complementary medicine
approaches for pain management
 Need more training and standardized protocols for
its integration into standard inpatient pain
management regimens
 More studies are needed to evaluate effectiveness
 Barriers: Insurance coverage and lack of knowledge
about integrative medicine providers
Neri CM, et al. Global Adv Health Med 2016;5:44-50
Evidence for Non-Pharmacologic Approaches
Lee C, et al. Pain Med 2014;15:S76-S85
Stress Reduction vs. Cognitive Behavioral Therapy
vs. Usual Care for Non-SCD Chronic Low Back Pain
Global Improvement of Pain (Pain Much Better or Completely Gone)
Week
8
26
52
Cherkin DC, et al. JAMA 2016;315:1240-1249