critical care of patients with sickle cell disease james h. hanson m.d. director of critical care...
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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
Pathophysiology of Sickle Hemoglobin
• Hemoglobin SS
• Hemoglobin SC
• Hemoglobin S-thal– abnormal red blood cell cytoskeleton– hemoglobin polymerization– impaired red cell deformability– impaired microvascular flow– increased endothelial activation
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
Acute Chest Syndrome
• intravascular clogging
• fat embolism
• atelectasis
• infection
• thromboembolism
Infectious Causes
• Staph aureus
• Strep pneumoniae
• Hemophilus influenzae
• Klebsiella pneumoniae
• Chlamydia
• Mycoplasma
• Viral
most common
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
Co-morbidities
• asthma
• marked anemia
• thrombocytopenia
• pulmonary hypertension
• cor pulmonale
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)
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
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
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
Therapy of Acute Chest Syndrome
• Unproven therapies, but “seem to work”– Dornase alfa inhaled– Nitric oxide– ECMO
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
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
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
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
Sepsis
• Chronic penicillin or amoxicillin is indicated due to functional asplenia
• Assure pneumococcal vaccination
• Follow Surviving Sepsis Campaign guidelines
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
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
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
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
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
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
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?
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