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