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Acute Chest Syndrome Sickle Cell Disease

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Acute Chest Syndrome Sickle Cell Disease Powered By Docstoc
					Acute Chest Syndrome
Presented By: Peter Andre Soltau Medical Class Of 2009

Sickle Cell Anaemia


Sickle cell anemia is the most common inherited genetic disease affecting African Americans.

•Jamaica: 2-5/1000

Sickle Cell Anaemia


This autosomal recessive disorder is characterized by a single amino acid substitution (glutamic acid to valine in position 6) in the beta subunits of the hemoglobin tetrameric protein.

Inheritance Of Sickle Cell Disease

Sickle Cell Disease
Forms of SCD  Sickle cell anemia (HbSS)  Sickle Hemoglobin C (SC)  Sickle Beta Thalassemia

Sickle Cell Disease Pathophysiology


Upon deoxygenation, hemoglobin S undergoes conformational changes. Polymerization with other hemoglobin tetramers occurs with the formation of long polymer chains that ultimately distort the erythrocyte membrane

Sickle Cell Disease Pathophysiology
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These irreversibly sickled cells diminish blood viscosity, causing haemolysis and obstructing the microcirculation of end-organ tissues.

Sickle Cell Disease Pathophysiology
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The sickle cells also produce thrombosis and obstruction in small vessels, leading to ischemia and necrosis of distal tissue. It is this resultant hypoxia and ischaemia which causes the pathologic and clinical features of the disease.

Prevalence


Trait Rate

10%

Prevalence of Sickle Cell Anaemia in Jamaica

Location St. Andrew Kingstonsb St. Mary St. Andrew Hanover Kingston

Age Group 35 – 64 35 – 64 7 - 15 9 – 11 0–5 10 mos

No. 1018 502 757 221 2364 270

%AS 12.0 9.0 9.1 9.5 9.8 9.3

SCD in The ED
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The most common paediatric genetic condition encountered in emergency medicine.

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Patients with SCD typically present to the E.D. because of complications The manifestations can be divided into: i. Vasoocclusive Crises ii. Haemotologic Crises iii. Infections

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Clinical Manifestations
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Vasoocclusive Crises (Classic “sickle crisis”)  Pain - most frequent complaint and it is usually ischemic in origin.  Most common reason for ED visits by children  Occurs when the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied

Clinical Manifestations
Vasoocclusive Crises
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Can involve : • Bones • Joints • Soft tissue • Dactylitis or as hand and foot syndrome (painful and swollen hands and/or feet in children
•

•

Abdominal Organs Central Nervous System

•

Lungs – Acute Chest Syndrome

Triggers: •Stress •Cold water exposure •Dehydration •High altitudes •Hypoxia •Infection (bacterial or viral)

Clinical Manifestations
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Haemotological Crises
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manifested by a sudden exacerbation of anemia, with a corresponding drop in the hemoglobin level. This can be due to acute splenic sequestration
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Sickled cells blocking splenic outflow, leading to the pooling of peripheral blood in the engorged spleen

Clinical Manifestations


Haemotological Crises
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Can also be caused by aplasia, in which the bone marrow stops producing new RBCs Aplastic crisis, resulting in an erythroid aplasia

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Most commonly seen in patients with Parvovirus B19 infection or folic acid deficiency

Clinical Manifestations


Infections


due to underlying functional asplenia in most adults with sickle cell anemia This leads to defective immunity against encapsulated organisms (eg, Haemophilus influenzae, Streptococcus pneumoniae. Mycoplasma pneumoniae, Salmonella typhimurium, Staphylococcus aureus, and Escherichia coli )

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Acute Chest Syndrome

Definition


Acute Chest Syndrome (ACS) is a spectrum of pulmonary pathology in a patient with sickle cell disease and is characterized by:
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Chest pain Fever (>38.5oC) Tachypnoea/dyspnoea Wheezing Productive cough Hypoxaemia New pulmonary infiltrates on chest x-ray New England Medical Journal 2000; 342: 1905

Incidence
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Occurs in ~ 50% of SCD patients Recurs in 80% Most common cause of death in SCD
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Accounts for 30% of deaths in children with SCD Associated with a mortality rate of 10 – 12%

 

Accounts for 12 – 15% of hospital admissions It is the second most common cause of hospitalization in persons with sickle cell anemia and accounts for 25% of premature deaths (1).

Incidence




The prospective Cooperative Study of Sickle Cell Disease observed in 3,751 subjects with sickle cell anemia a 29% incidence of ACS over a 2-yr period (27). This translates into an attack rate of 12.8 episodes/100 patient years for homozygous sickle cell disease. ACS rates vary directly with : 1) steady-state leukocyte counts 2) hemoglobin concentration, and, 3) inversely, with age and hemoglobin F levels.
27. Castro, O., D. J. Brambilla, B. Thorington, C. A. Reindorf, R. B. Scott, P. Gillette, J. C. Vera, and P. S. Levy. 1994. The acute chest syndrome in sickle cell disease: incidence and risk factors. Blood 84: 643-649

Incidence cont’d
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Incidence highest in:
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HbSS disease (homozygous)
Hb SS = Hb S ß0-thalassemia > Hb SC = Hb S ß+-thalassemia.

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Younger age (<10 yrs old) – peaks at age 2-4 Patients with a high steady-state Hb level and low [HbF] Patients with a high steady-state leukocytosis

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ACS in Jamaica
SC Clinic SC SS Clinic SS 0.0 2.5 5.0 7.5 10.0 12.5

Incidence /100 person-years

Incidence of ACS by Age

Case Fatality per 100 events JSSCD
Cause of death Male Female ALL

CVA
Septicaemia

37.5
23.53

8.33
23.68

27.78
23.61

ASS
ACS

2.86
1.63

8.89
5.42

5.64
3.14

Aetiology Classification
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Hb S related
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Direct Consequence of HbS Indirect Consequence of Hb S

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Not related to Hb S

AETIOLOGIES
Hemoglobin S related
Direct consequences of Hb Indirect consequences of Hb S

Unrelated to Hb S

-pulmonary infarction - in situ sickling -fat embolism syndrome -hypoventilation secondary to 1) rib/sternal bone infarction 2) narcotic administration (opiod analgesics) -Acute pulmonary edema induced by narcotics or fluid overload

Infections:
e.g Pneumonia:
i. ii. iii. iv.

Bacterial Viral Fungal Protozoan

-fibrin thromboembolism -foreign body/intrinsic bronchial obstruction -opportunistic infection related to HIV-1 infection -acute sarcoidosis -other common pulmonary diseases (e.g., aspiration, trauma,

Pathophysiology
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Pulmonary Infection/Infarction
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SCD patients are at increased risk of infection Impaired access of oxygen to inflamed and consolidated lung Regional hypoxia Local sickling and vaso-occlusion leading to micro-cascular occlusion within the pulmonary vasculature with later pulmonary infarcts Increased erythrocyte adhesion to the endothelium to thrombosis N.B. Infarction leads to hypoventilation which predisposes to infection

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Pathophysiology cont’d
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Fat Embolism
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Patient may develop ACS within 1 – 3 days of painful crisis Painful crisis results in bony infarction May produce fat emboli which travel in circulation Emboli become lodged in the pulmonary vessels causing mechanical obstruction and an acute inflammatory response

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Rib/Sternal Infarctions
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A sequence of infarction, pain and inflammation, conscious hypoventilation due to splinting resulting in hypoxemia and subsequent atelectasis.

Pathophysiology cont’d


Regardless of initial insult, final picture is a constellation of:
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Microvascular occlusion due to sickled red cells and increased red cell adhesion to vascular endothelium Disturbance of endothelial vasoactive mediators Release of inflammatory cytokines due to infection and vascular injury Activation of the coagulation cascade Fat embolism from bone marrow infarcts Exaggerated pulmonary vasoconstriction due to regional hypoxia

Clinical Features


Symptoms :
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Pleuritic chest pain Shortness of breath
Productive cough

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Fever (>38.5oC) +/- pain in arms, legs and abdomen

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Clinical Features cont’d
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Symptoms at presentation age-dependent:
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< 10 yrs of age
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Fever(>38.5oC) Cough Wheezing

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Adults
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Pain in arms and legs Dyspnoea

Clinical Features cont’d
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Signs
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Ill-looking
Tachypnoea/ signs of respiratory distress Febrile (>38.5oC)

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Chest wall tenderness Dull percussion note

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Rhonchi Rales

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History
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Previous haemoglobin levels Previous blood transfusions Past Medical History
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Hospitalizations Allergies Vaccination
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Pneumococcal vaccination Influenza vaccination Hepatitis B vaccination

History
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Drug History
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Previous intake of analgesics (type and dose)

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Surgical History
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Splenectomy – increases the likelihood of a an infectious crisis

Physical Examination


Vital Signs
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Increased
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Respairatory Rate- Tachypnoea Temperature Pulse Rate

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General
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Observe for pallor, icterus, and erythema or edema of the extremities or joints

Physical Examination
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Respiratory
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Tachypnoea Chest wall tenderness 2o to rib infarction Dullness to percussion – pleural effusion Auscultate – rales *may be normal in 35%

Management
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Investigations
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Complete blood count
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Hb below steady-state values Leukocytosis above steady-state values – all patients with SCD

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Major elevation in the WBC count (ie, >20,000 per mm3) - suspicion for infection.
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Thrombocytosis/thrombocytopenia

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Blood group and cross-match

Management
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Cultures of sputum and blood - Should be obtained in any SCD patient with temperature > 38.4oC - Done in any child with radiographic evidence of infiltrative disease

Arterial Blood Gas
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May be ordered in patients who are in respiratory distress to supplement information provided by oxygen saturation monitoring. Reflect the severity of pulmonary crisis. Serial ABGs are necessary to follow the response in pulmonary crisis. Usually done to have a baseline reference

Chest X-ray
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May initially be normal Findings include  New pulmonary infiltrates  LZ>MZ>UZ
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patchy lower-lobe involvement in a segmental, lobar, or multilobar distribution, with or without pleural effusion

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Presence of bilateral pulmonary infiltrates -patients are more likely to have serious illness

Chest Radiograph
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May initially be normal Infiltrates takes two to three days to become apparent The infiltrate often will begin in one lobe and progress to other lobes

Differentials
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Acute chest syndrome\pulmonary infarction
Pneumonia (bacterial or viral)

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Pulmonary thromboembolus

Treatment
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The mainstay of successful treatment is high quality supportive care. Consultation with pulmonary, infectious disease and intensive care specialists is a necessary part of management. Fluid management, oxygenation, chest physiotherapy, bronchodilators, and intermittent incentive spirometry are essential elements of management in the absence of a specific therapy that consistently ameliorates clinical course.

Treatment
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Initial Stabilization
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Airway, Breathing, Circulation Identify and treat high morbidity complications
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Chest Crisis Sepsis Splenic sequestration Cerebrovascular Accident

Management cont’d
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Maintain adequate oxygenation - Supplemental oxygen to maintain PaO2 between 70 -100 mm Hg - If severe respiratory failure – intubation and use mechanical ventilation Prevent further alveolar collapse by using incentive spirometry (SMI) - Encourages deep inspiratory effects that result in less hyperventilation and atelectasis - Improve arterial oxygenation

Management cont’d
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Improve oxygen carrying capacity of the blood
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Simple blood transfusion – 1-2 untis
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Leukocyte-depleted, matched Clinical deterioration PaO2 < 60mmHg Worsening on CXR Goal: HbS to 20 – 30% and PCV to 30%

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Exchange transfusion if
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Management cont’d
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Consider early transfusion for  Patients at high risk for complications  Adults  Cardiac disease  Severe pain in arms and legs at presentation
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Severe anaemia, thrombocytopenia or both

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Multilobar pneumonia

Pain Management
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Control Pain
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Give adequate amounts of narcotic analgesics to alleviate pain, avoiding hypoventilation from excessive sedation
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Morphine Sulphate 0.1-0.15 mg/kg every 34 hours IV Meperidine 0.75 – 1.5 mg/kg every 2-4 hours IV Acetaminophen 15mg/kg po q 4 hr or prn if T> 38.0

Management cont’d
Bronchodilators
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Should be given to all patients Airway hyper-reactivity assumed present regardless of presence (or absence) of audible wheeze Use albuterol inhaler or nebulizer This helps to reduce the chances of hypoxaemia via bronchodilation and thereby preventing further sickling

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Management cont’d
Maintain adequate fluid volume / Hydration - 1.5 of maintenance is given after deficits have been corrected  Adults and Children- 0.45% Normal Saline  Infants - 5% Dextrose in 0.25% Normal Saline
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Hypotonic saline (5% dextrose in 0.25% normal saline IV) to maintain normovolaemic state or reverse intravascular volume depletion  Dehydration increases plasma osmolality and intracellular dehydration of red blood cells  Hypotonic saline enters the red blood cells reducing the tendency to sickle Overzealous hydration may cause pulmonary oedema

Antibiotic Therapy
Guidelines regarding role of antibiotics not firmly established  Patients should receive empirical broad spectrum antibiotics including a macrolide e.g. a 3rd generation cephalosporin + erythromycin
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If infection is suspected: Cefotaxime or Cefuroxime 50mg/kg q 8 h IV  Azithromycin 10mg/kg po first dose, then 5mg/kg qd, Erythromycin 10mg/kg q 6 h po


Treatment
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Corticosteroids
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Recent study in children found that dexamethasone 0.3mg/kg q12h for 4 doses reduced
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Mean hospital stay Analgesic requirements Need for blood transfusions

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Postulated that beneficial effects due to inhibition of the inflammatory response thereby reducing bronchoconstriction

Treatment


Inhaled Nitric Oxide:
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Causes dilation of blood vessels in the lungs thereby increasing the oxygen-carrying capacity of the blood and reducing hypoxaemia

Treatment-Prophylaxis
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Hydroxyurea:
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Stimulates the production of healthy fetal haemoglobin in order to inhibit the sickling process Reduces the recurrence of ACS

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Complications
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Pulmonary
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GI
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Respiratory failure Pneumothorax Empyema Pulmonary Haemorrhage
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Haemmorrage Ileus Bowel infarction Splenic Sequestration

Renal Failure

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Cardiac
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Arrhythmias CCF

Complications
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Neurological sequelae:
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altered mental status anoxic brain injury intra-cerebral bleed Infarction Seizure

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Death:
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Respiratory failure Splenic sequestration Pulmonary haemorrhage Cor pulmonale Sepsis seizure

Admission Criteria
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All patients with Acute Chest Syndrome are admitted

Prevention


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Factors which predispose to the development of acute chest syndrome and pneumonia are still being defined. Incentive Spirometry should be used for all postoperative patients and hospitalized patients with pain in the thorax or back (REF Bellet 1995).

Prevention
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Daily treatment with hydroxyurea: decreases the rate of recurrent acute chest syndrome in adults and children. Smoking and exposure to passive smoking should be avoided.

Prevention
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Children and adults should receive appropriate vaccination including H. influenzae, pneumococcal, and annual influenza vaccine. Patients with sickle syndromes and upper respiratory syndromes should be treated with antibiotics if fever, sinus drainage, or productive cough develops. Periodic evaluation of pulmonary functions may identify individuals at risk for chest syndrome

Patient and Parent Education
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Parents should be instructed to provide prophylactic penicillin, keep immunizations up to date, and take the child to the physician for evaluation of upper respiratory symptoms, cough and fever. Smoking by patients and around patients should be actively discouraged. All hospitalized patients should be issued an incentive spirometer.

In Summary
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ACS, the second most common reason for hospitalization in a SCD patient, is an acute illness characterized by fever and development or worsening of respiratory symptoms, accompanied by a new pulmonary infiltrate on chest radiograph. Patients often present to the ED with pleuritic chest pain, cough and dyspnea. Diagnostic workup of acute chest syndrome includes chest radiograph, pulse oximetry and/or arterial blood gases, CBC, and reticulocyte count. Treatment is guided by the severity of the disease, but always includes hydration, pain control, and oxygen therapy.

THE END THANK YOU FOR YOUR TIME ! !

Bed rest and provision of warmth and a calm relaxing atmosphere Distraction where appropriate Oral fluids at 3 litres/24 hours IV fluids if reluctance to drink or vomiting or to correct dehydration Oxygen at 3 L/min if oxygen saturation below steady state (or if < 90% if steady state unknown) Patients with rib pain should be encouraged to breathe deeply and slowly at regular intervals

Moderate
Paracetamol 1gm POq4-6h +/Diclofenac sodium 75-100 mg PO/IM q8h +/Codeine phosphate 30-60 mg PO q4-6h or Tramadol 50-100 mg PO/IM q6h

Severe

Paracetamol 1gm POq4-6h +/Diclofenac sodium 75-100 mg PO/IM q8h + Pethidine 100-150mg PO q4h or 50-100 mg IM q2-4h or Morphine 10 – 20mg PO/SC/IM q3-4h

References


Sergeant, G.R. Sickle Cell Disease 2nd Edition. Oxford University Press 1992, New York

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Ballas, S.K. Sickle Cell Pain, Progress in Pain Research and Management Volume II. IASP Press 1998, Washington Vichinsky, E.P. et al. Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease. New England Medical Journal 2000; 342: 1855-1865 Yale, S.H. et al. Acute Chest Syndrome in Sickle Cell Disease – Crucial considerations in adolescents and adults. Postgraduate Medicine 2000; 107

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