Critical Care of Patients with Sickle Cell Disease

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Critical Care of Patients with Sickle Cell Disease

• James H. Hanson M.D.
• Director of Critical Care
• Childrens Hospital Research Center Oakland
• Associate Clinical Professor of Pediatrics
• UCSF

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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

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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

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Acute Chest Syndrome

• intravascular clogging
• fat embolism
• atelectasis
• infection
• thromboembolism

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Infectious Causes

• Staph aureus
• Strep pneumoniae
• Hemophilus influenzae
• Klebsiella pneumoniae
• Chlamydia
• Mycoplasma
• Viral

most common
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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

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Co-morbidities

• asthma
• marked anemia
• thrombocytopenia
• pulmonary hypertension
• cor pulmonale

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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)

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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

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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

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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

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Therapy of Acute Chest Syndrome

• Unproven therapies, but seem to work
• Dornase alfa inhaled
• Nitric oxide
• ECMO

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Cerebral Vascular Accident

• 300X gt 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 lt 30

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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 lt 30 and
  Hgb 10-11 mg/dL
• Avoid extremes of blood pressure
• Normal BP is lower in sickle cell patients
• Avoid hyperglycemia

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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

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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

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Sepsis

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

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Iron Overload

• Results from gt 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

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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

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Transfusion

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

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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 lt 30
• Blood exposure precautions
• Use blood warmer

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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

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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

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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?

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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