(Summarized from lectures by Drs. Prasad and Fletcher)
 

Sickle Cell Disease

• Inherited disease. Change in hemoglobin
• normal adult Hgb A: alpha and beta units
• Hgb S
• variant of beta chain
• substitution of valine for glutamic acid
• with deoxygenation, RBC deforms to sickle-shape. Cells polymerize, making blood thick, gel-like.
• Diagnosis
• Hgb electrophoresis
• Several variants, including SA, SC (Cooley), Sthalassemia

Sickling

• begins at PO2 40-50mmHg
• greatest when PO2<20
• vascular stasis, with localized hypoxia
• likelihood of sickling related to amt of Hgb S
• Hgb SS: 70-98% Hgb S, rest Hgb F
• Hgb SA: 10-40% Hgb S
• Hgb SC: sickling propensity between SA and SS
• organs with sluggish circulation, high oxygen extraction and low pH are most vulnerable
• spleen, bone marrow
• reoxygneation reverses polymerization (e.g., when blood passes through lungs)
• lungs protect arterial circulation
• injured, under-ventilated lung becomes ‘spleen-like’. Sickled cells adhere to its activated endothelium, fail to reoxygenate and ultimately cause more inflammation and lung infarction which may cause Acute Chest Syndrome.

Clinical Manifestations

• Long periods of health punctuated by episodic painful crises and chronic organ damage
• painful crises: 0.8 episodes/year
• Acute chest syndrome
• SA
• nl life expectancy
• sickling only with extreme hypoxia (e.g., PaO2 20 mmHg)
• SS
• Chronic anemia
• Chronic hemolysis --> inc bili, inc incidence cholelithiasis
• Generalized pulmonary fibrosis --> inc Aa gradient
• Cor pulmonale, eventually
• Renal medulla infarction/necrosis; inability to concentrate urine, dec. GFR, nephrotic syndrome
• Splenic infarction; inc susceptibility to infxn
• Neurologic dysfnct from cerebral vessel occlusion/hemorrhage
• Priapism
• Usually die by age 30
• SC
• mild anemia (Hgb 10-11)
• crises less common than SS, more than SA

pulm dysfnct from URI, pneumonias, and pulmonary embolization relatively common

Acute Chest Syndrome

• Definition
• New pulmonary infiltrate in one lung segment (not atelectasis)
• Chest pain
• Temperature over 38.5 degrees C
• Tachypnea, wheezing or cough
• leading cause of morbidity and mortality
• 0.13 episodes/year
• most common condition at time of death
• Clinical course (Vichinsky et al. NEJM 2000; 342:1855)
• 13% - mechanical ventilation
• 11% - neurological symptoms
• 9% (>20 years old) died
• In half cases a painful vaso-occlusive crisis occurred 2.5 days before CXR abnormalities
• Causes: fat embolism, infection (38%)
• 16% had pulmonary infarction as initiating event
• Chlamydia, mycoplasma, viral
• Associated with lung infarction
• Lower lobe involvement often bilateral
• 55% had effusion
• Mean SpO2: 92% on air at diagnosis
• Younger pts less likely to receive oxygen or mechanical ventilation
• 19% of ventilated patients died
• Treatment
• Oxygen, fluids, warm
• Oxygen indicated for SaO2 <60 mmHg or SpO2 < 90%
• Bronchodilators for wheezing
• Red-cell transfusion, with/without exchange – 68%
• Exchange if Hb is anemia ‘less severe’
• Mean of 3.2 units
• Transfusion increased SaO2 from 63 to 71 mmHg

Treatment - Chronic

• No cure; goal is to prevent sickling.
• Avoid hypoxia, hypoperfusion (hypotension, hypovolemia), acidosis
• Hydroxyurea
• Increases fetal hemoglobin
• Reduces painful crises and chest syndrome by 50%
• Fewer episodes of fat embolism from infarcted bone marrow
• Decreased white count decreases inflammatory response thus reducing polymerization on activated endothelium

Surgery and Sickle Cell Disease (Koshy et al Blood 1995; 86:3676)

• 1978-1988, 3765 patients, 5.3 years mean follow-up
• 1079 surgical procedures on 717 patients
• 77% SS, 14% SC, 5.7% Sbetao thalassemia, 3% Sbeta+ thalassemia
• Cholecystectomy (23 ± 11 yr) or splenectomy (8 ± 8 yr) were most common (24% of procedures)
• 12 deaths in 1079 procedures (1.1%)
• 3 related to surgery/anesthesia (0.3%)
• No deaths under 14 years of age
• Summary
• Low complication rate in minor procedures without transfusion
• SC disease always did better with transfusion
• Tonsillectomy did well without transfusion
• Young age group
• Optimum anesthetic techniques cited but not specified
• Optimum Hb S reduction not well quantified
• Transfuse to Hb of 10g/dl
• Risks of transfusion are apparent

Pregnancy and Sickle Cell Disease

• Transfusion
• if crises occur
• if severe anemia, hypoxemia, preeclampsia, septicemia, renal failure, acute chest pain syndrome, anticipated surgery
• goal=Hgb> 8 g/dL, Hgb S < 60%
• Partial exchange transfusions vs. simple transfusion
• CLE recommended
• excellent pain control
• decrease catecholamines
• Operative delivery
• regional vs. GA: use other factors to choose

Management of Anesthesia

• Avoid hypoxia, vascular stasis, acidosis
• Preop sedation: d/n depress ventilation
• Supplemental oxygen
• Transfusion? (See Surgery and SCD, above)
• Regional anesthesia
• give supplemental O2
• may produce compensatory vasoconstriction and decreased oxygen delivery to nonblocked areas
• Avoid acute hypovolemia
• Tourniquets
• controversial
• no definitive studies
• risk of sickling due to stasis
• Maintain normothermia
• fever increases rate of gel formation by Hgb S
• hypothermia retards gel formation, but also produces vasoconstriction