Sickle Cell Disease & ICUDr Muhammad Asim Rana MBBS, MRCP, EDIC, FCCP, SF-CCM

Department of Critical Care Medicine

IntroductionSickle cell disease (SCD), an inherited disorder due

to homozygosity for the abnormal hemoglobin, hemoglobin S (HbS).

Hemoglobin S (HbS), results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain, which produces a hemoglobin tetramer (alpha2/beta S2) that is poorly soluble when deoxygenated.

Characteristic Sickle Shaped RBCs

Major Clinical MenifestationsAnemia Vaso-oclusive Crises

Episodes of ischemic pain (i.e., painful crises) Ischemic malfunction or frank infarction in the

spleen, central nervous system, bones, liver, kidneys, retina & lungs.

AnemiaChronic AnemiaAcute severe anemia 

There are three settings in which an acute fall in hemoglobin concentration may be superimposed upon the chronic anemia

1.Splenic sequestration crisis 2.Aplastic crisis 3.Hyperhemolytic crisis

Vaso-occlusive crisis & its effectsAcute painful episodesMulti organ failureEffect on growth and

developmentPsychosocial effectsInfectionCVABone ischemia &

infarction

Cardiac –MIDermatological---Leg

ulcerHepatobiliaryPulmonaryRenalRetinopathyEffects on pregnancyPriaprism

Acute Chest Syndrome  The acute chest syndrome (ACS) is the most common form

of acute pulmonary disease in patients with SCD, occurring in almost one-half of patients.

It is the most frequently reported cause of death in adults, and is a risk factor for early mortality.

Definition of Acute Chest Syndrome Presence of a new pulmonary infiltrate, not due to

atelectasis, Involving at least one complete lung segment Chest pain Temperature >38.5ºC Tachypnea, wheezing, or cough

Etiology Causes can be listed as:

1. Unknown cause 2. Pulmonary infarction 3.Fat embolism 4.Chlamydia pneumoniae infection 5.Mycoplasma pneumoniae infection 6.Viral infection 7.Mixed infections 8.Other pathogens

Clinical findings  Patients with ACS present with

feverchest painextremity pain, dyspneanonproductive cough

Examination of the chest may reveal local tenderness over the ribs or sternum; findings of pulmonary consolidation may also be noted.

Common laboratory findings Leukocytosis Thrombocytopenia or thrombocytosis Falling hemoglobin concentration Elevations in lactate dehydrogenase High Bilirubin levels Chest Radiographs

Diagnosis of Acute Chest Syndrome No current laboratory or radiographic finding permits the

differentiation of ACS from other acute pulmonary manifestations of SCD, including pneumonia and infarction.

The finding of pulmonary infiltrate should be treated as infectious pneumonia (assume both are present) until proven otherwise.

Pulmonary infarction due to PE or ACS?

This differentiation remains problematic. Lack of evidence for DVTAbnormal ventilation-perfusion scans Inability to safely perform contrast studies

in these patients because of the possible association with further sickling.

Investigations for ACS1. Steady state Hb% & Hb electrophoresis2. CBC, Retics & peripheral film3. Blood Cultures4. Urine microscopy & cultures5. CXR6. U&E7. Blood group & antibody screening8. ABGs & Pulse oxymetry

Acute Management Clinical severity of Acute Chest Syndrome is broad. Close monitoring of progressive pulmonary changes and

escalating severity because the clinical status of these patients can quickly deteriorate if the underlying pulmonary insult is not reversed.

Therapeutic Interventions The goals of therapy are

To correct underlying factors that contribute to deoxygenation of hemoglobin including dehydration & Infections

To control painTo support the patient’s respiratory &

haemodynamic status

Fluid Management If dehydration is present, it should be corrected as

hypovolemia can contribute to increase sickling. Once it is corrected, euvolemia should be

maintained. Overhydration or rapid hydration should be avoided Weights should be monitored daily along with

intake/output for assessment of the fluid status and management of the patient

Infections  Broad spectrum empiric coverage with a third generation cephalosporin (eg, cefotaxime or

ceftriaxone) for common bacterial coverage and a macrolide (eg, azithromycin or erythromycin) for

coverage of atypical organisms (such as mycoplasma and chlamydia)

should be initiated immediately on admission.

Pain controlOpiates (Morphine, Diamorphine, Pathedine)

KetorolacTramadolEpidural AnalgesiaMethylprednisolonePoloxamer 188

Respiratory support  Oxygen supplementation should be provided to maintain

arterial oxygen saturation ≥ 92 percent. Incentive spirometry, preferably supervised by a clinical

worker, should be employed at least every two hours to prevent atelectasis from hypoventilation.

Patients with poor respiratory effort or rising oxygen requirements Use of positive pressure ventilation devices such as

nasal mask continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) may be useful.

Patients with respiratory failure and acute respiratory distress syndrome

Conventional or high-frequency oscillatory mechanical ventilation can be used.

Other respiratory interventions Inhaled nitric oxide Extra corporeal membrane oxygenation Bronchoalveolar lavage

(Bronchoscopy with bronchoalveolar lavage (BAL), usually reserved for patients with severe or progressive infiltrates, provides both diagnostic and therapeutic benefits. Bronchial samples can be examined for lipid content in alveolar macrophage as evidence for pulmonary fat embolism and also sent for culture. In intubated patients, bronchoscopy with suction and removal of bronchial casts has been reported to improve patient ventilation)

Transfusion In patients with ACS, transfusion therapy should be

considered early in the course of the disease.

Simple TransfusionExchange Transfusion

Simple Transfusion The goal of simple transfusion is to increase the

hematocrit (Hct) to 30 percent or hemoglobin (Hgb) to 11 g/dL.

To improve oxygenation For accentuated anemia For patients with clinical or radiological progression

of disease but not impending respiratory failure. For patients in whom exchange transfusion will be

delayed.

Exchange Transfusion Neurological involvement Lung involvement (PaO2<9kPa with FiO2>60%) Rapidly falling haemoglobin Priaprism

Complications Neurologic events may complicate the course of ACS,

particularly when patients have severe pulmonary disease and/or respiratory failure, including;

Reversible posterior leukoencephalopathy syndromeSilent cerebral infarctsAcute necrotizing encephalitis

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