Critical Care of Patients with Sickle Cell Disease

1. Critical Care of Patients with Sickle Cell Disease James H. Hanson M.D. Director of Critical Care Children’s Hospital & Research Center Oakland Associate Clinical Professor of Pediatrics UCSF

2. Pathophysiology of Sickle Hemoglobin • Hemoglobin SS • Hemoglobin SC • Hemoglobin S-bthal • abnormal red blood cell cytoskeleton • hemoglobin polymerization • impaired red cell deformability • impaired microvascular flow • increased endothelial activation

3. Acute Chest Syndrome • Pulmonary infiltrates • sometimes with effusion • with one or more of the following: • Chest pain • 40% also have abdominal pain • Fever • Impaired oxygenation • May also have chills • Often preceded by vaso-occlusive crisis • high phospholipase A-2 levels

4. Acute Chest Syndrome • intravascular clogging • fat embolism • atelectasis • infection • thromboembolism

5. Infectious Causes • Staph aureus • Strep pneumoniae • Hemophilus influenzae • Klebsiella pneumoniae • Chlamydia • Mycoplasma • Viral most common

6. Vicious Cycle • sickling worsens with hypoxemia, acidosis • atelectasis causes vasoconstriction • sluggish flow and more occlusion • chest pain causes splinting • underaeration and atelectasis • narcotics for pain may decrease ventilation • increased atelectasis • increased PaCO2 increases acidosis

7. Co-morbidities • asthma • marked anemia • thrombocytopenia • pulmonary hypertension • cor pulmonale

8. One thing leads to another • acute chest syndrome often recurs • gradual scarring • restrictive lung disease • pulmonary hypertension • even without overt acute chest episodes • cor pulmonale • 20% of patients with ACS develop neurologic complications (often beginning with confusion)

9. Therapy of Acute Chest Syndrome • Oxygen • avoid excess which reduces erythropoiesis • Careful rehydration • maintain euvolemia • judicious use of furosemide often helpful • Antibiotics • erythromycin or azithromycin • cefuroxime • Pain control • narcotics • ketorolac • acetaminophen

10. Therapy of Acute Chest Syndrome • Improve oxygen delivery • reduce % hemoglobin S • packed red cell transfusion – early on! • exchange transfusion if still worsening (rarely needed if transfused early) • bronchodilators • albuterol regardless of presence or absence of wheezing • non-invasive ventilation • endotracheal intubation • adequate PEEP • incentive spirometry

11. Therapy of Acute Chest Syndrome • Dexamethasone may shorten course • However, use of steroids associated with: • 1/3 of patients are readmitted • Increased risk of avascular necrosis • Pancreatitis • Mental status changes • Clinical trial being designed

12. Therapy of Acute Chest Syndrome • Unproven therapies, but “seem to work” • Dornase alfa inhaled • Nitric oxide • ECMO

13. Cerebral Vascular Accident • 300X > control patients without sickle cell disease • 11% with HgbSS will have CVA by age 15y • 2% of patients with HgbSC • 17-22% of Hgb SS patients have “silent” CVAs • Abnormal MRIs in 1/3 of patients by age 15 • Abnormal transcranial Doppler:  risk •  risk if baseline Hgb low or WBC high • Higher risk if BP normal to high • Higher if patient has moya-moya collaterals • Strokes reduced with chronic exchange transfusion • keep % Hgb S < 30

14. Cerebral Vascular Accident • Standard management of airway, breathing, and circulation • More concern about hyperosmolar therapy • could induce more sickling • Transfuse and/or exchange to keep HgbS < 30% and Hgb 10-11 mg/dL • Avoid extremes of blood pressure • Normal BP is lower in sickle cell patients • Avoid hyperglycemia

15. Splenic Sequestration • 15% of Hgb SS patients between 6-36 months • Rapid enlargement of spleen • Drop in hemoglobin • Rise in reticulocytes • Drop in platelets • Shock • Hemoglobinuria and renal failure • Liver sequestration rare • Rhabdomyolysis rarely

16. Splenic Sequestration • Support intravascular volume • Pain control • Transfusion and rarely exchange • Splenectomy if recurrent or refractory • Immunize to pneumococcus; meningococcus • When liver involved, may need vitamin K • Closely monitor urine output

17. Sepsis • Chronic penicillin or amoxicillin is indicated due to functional asplenia • Assure pneumococcal vaccination • Follow Surviving Sepsis Campaign guidelines

18. Iron Overload • Results from > 20-30 units PRBCs • Desferoxamine (or deferiprone) for iron chelation • Cardiac dysfunction and CHF • Pancreatic disease and diabetes mellitus (no DKA) • Hepatic dysfunction • hepatocellular carcinoma • Hypothalamic pituitary dysfunction • sex hormone deficiency

19. Iron Overload • Manage organ dysfunction as usual • Continuous desferoxamine infusion • Deferiprone (L1) available in many countries - may help • Other newer agents becoming available • May be eligible for solid organ transplant

20. Transfusion • Preoperative transfusion to Hgb 9-10 gm/dl improves morbidity • Avoid Hgb > 12 gm/dl (hyperviscosity) • Sickledex negative blood • Phenotypically match, at least to C, E, Kell • high rate of alloimmunization • Leukodepleted blood

21. Exchange transfusion • Use only if straight transfusion inadequate • Pheresis machine preferable • Manual exchange acceptable • dilute PRBCs with 5% albumin or NS to Hct 30 • monitor vital signs closely • May need calcium • 150 mL/kg removed and replaced (“double volume”) should reduce %S to < 30% • Blood exposure precautions • Use blood warmer

22. Priapism • Painful, prolonged erection • Difficult to treat • Hydration, but not excessive • Narcotics • Transfusion not usually successful • Urologic injection/aspiration • Erectile dysfunction common sequela • especially in older patients

23. Future directions • Sildenafil reduces pulmonary hypertension • improves exercise endurance • Gardos channel blockers (not yet available) • improve intraRBC dehydration • improve markers of hemolysis • Arginine + hydroxyurea improves available nitric oxide, and may help vasculopathy

24. Hematopoietic Cell Transplant • BMT or other stem cell transplant can be a curative therapy for SCD • About 90 % survival • About 80% disease-free survival • Gonadal dysfunction • Minority have progression of lung disease • if prior lung disease present • Best candidates those who have had mild cerebrovascular accidents • Best outcomes in minimally-transfused • But how do you predict who is at risk?

25. Perioperative Management • Preoperative transfusion improves morbidity • Highest risk of acute chest syndrome in first 48 hours after surgery • Outpatient surgery may be ill-advised • Better outcomes with laparoscopy