Tips for the anaesthetist- sickle cell disease

1. Sickle cell disease
Dr. Malaka Munasinghe
Registrar in anaesthesia
2017.10.25

2. History
• 1904-journal ‘SCIENCE’
• a ‘peculiar anomaly in human red blood corpuscles. . . Examination disclosed
the fact that the colored corpuscles . . . were elliptical and not circular’- sickeled
• Identified in a healthy black medical student
• Died an year later following an episode of tonsillitis later believed to be of catastrophic
complications of sickle cell disease
• The pathophysiology and genetic predisposition identified later

3. Sickle cell disease
• Haemoglobinopathy and a chronic inflammatory disorder
• Genetic inheritance transferred in autosomal recessive pattern
• Mainly seen among African people-lesser in Mediterranean and South Asian
countries
• Incidence- 1 in every 3 births in African-American people- sickle traits
I in 650 African- American people- sickle cell disease
 Seen in sri lanka-exact data not available

4. Haemoglobinopathies
 Defect in a haemoglobin chain or underproduction of a haemoglobin chain
 Underproduction- Thalassemias
 Defective hemoglobin chains seen in sickle cell disease

5. Sickle cell disease
 Mutation in Chromosome 11
 glutamine (at the sixth position) on the beta chains of the haemoglobin
molecule replaced by valine- HbS
 Instead of HbA- HbS is produced
 If Both HbA and HbS(20-45%) is produced
- sickle trait
If HbS 85-95%- Sickle cell disease

6. Pathophysiology
 In deoxygenated state HbS polymerizes and comes out of solution
 Forms long crystals- tactoids
 Disrupt the membrane shape- sickling
 Initially reversible- repeated sickling leads to permanent sickle shape with
small vessel occlusion
- premature destruction ( life span- 20days- chronic
haemolytic anaemia

7. Pathophysiology- sickle traits
 In sickle traits- sickling occurs in lower venous O2 tensions compared to
patients with sickle cell disease
 Clinically-asymptomatic

8. Sickle cell disease
 Multi system disorder
 Usually clinically evident when Hb A production is dominant around 4-6 months
of age
(severity of the disease is reduced in sickle cell disease patients who have HbF)

9. CVS
 Cardiomegaly due to chronic anaemia and high cardiac output state
 Congestive cardiac failure
 Pulmonary hypertension due to recurrent pulmonary infarcts

10. Respiratory system
 recurrent pulmonary infarctions - ‘acute chest syndrome’
( Dyspnoea, cough, haemoptysis, and pleuritic chest pain)
 Repeated episodes –pulmonary fibrosis and restrictive lung disease-respiratory
failure
 Reduced lung volume for gas exchange
 Affinity of HbS to O2???
 ODC ????

11. Acute chest syndrome(ACS)
 Medical emergency
 Pulmonary vaso-occlusion due to sequestration of sickled cells in small pulmonary vessels
 Second most common reason for hospitalization
 Mortality 2-12%; accounts for 25% of deaths in sickle cell patients
 Characterized by acute respiratory symptoms(fever, tachypnea, pleuritic pain & cough)
concurrent with new lobar infiltrate on CXR
 Spectrum of pathology:
 Infection
 Infarction (ribs)
 Fat embolism
 Infection or fat emboli may lead to vaso-occlusion & sequestration
 Significant association with STROKE

12. Gastrointestinal
 Initial splenomegaly in early childhood
- sudden trapping of blood cells- Splenic sequestration crisis with
severe anaemia and shock
 later- autoinfarction of spleen due to vaso-occlusion- immune incompetence
 Chronic haemolysis- increased production of bile stones- frequent cholecystectomies
 Elevated transaminases- otherwise- LFT spared

13. Head/neck/airway
 Marrow hyperplasia- frontal bossing and a prominent maxilla- Difficult air way
 Functional asplenism due to autoinfarction –hypertrophy of other lymphoid
tissue (tonsils and adenoids)- obstructive sleep apnoea
 Eye changes- microvascular retinopathy/ vitreous haemorrhage/retinal
detachment

14. Renal
 Renal impairement begin in childhood
 Common in adults with loss of ability to concentrate urine/ albuminuria/
microscopic haematuria with renal infarcts
 Painful priaprism( sustained, painful erection)- due to occlusion of penile
venous plexuses

15. Skeletal/skin
 Marrow hyperplasia/ repeated vasoocclusive episodes- bone deformities
 Aseptic necrosis
 Leg ulcers/osteomyelitis

16. Neurological
 Increased incidence of TIA/ Haemorrhagic and ischaemic strokes

17. Haematological
 Splenic sequestration crisis
 Aplastic crisis- reduced RBC production due to marrow failure associated with viral
infections- Parvo B19
 Hperhaemolytic crisis- associated with transfusion reactions, viral infections or G6PD
deficiency
 Chronic blood transfusions - iron overload with cardiomyopathy/ hepatic and
bone marrow fibrosis/ growth retardation
- alloimmunisation
- fluid over load
 Increased risk of deep vein thrombosis- stasis due to venous obstruction with red cells/
platelet activation/ thrombocytosis following splenectomy/ endothelial dysfunction

18. Vaso-occlusive crisis
 Acute painful crisis
 occurs in long bones, ribs, spine, or abdomen
 Precipitants: infection, dehydration, hypothermia, hypoxia, stress, alcohol intake,
menstruation
 Bone pain from ischemia & infarction of marrow or cortex
 Abdominal pain from bowel ischemia, organ infarction, or referred from the ribs- may
mimick acute abdomen
 Anesthesia may be requested to assist with analgesia (e.g., patient-controlled analgesia)

19. Diagnosis of sickle cell disease
 In emergencies- ‘sickledex test’ – a rapid screening test -will detect HbS of
>10%
 Screening test should be done in all patients coming from endemic areas
 Do not differentiate the sickle traits
 Confirmed by Hb electrophoresis- demonstrate HbSS
 Demonstrate associated Hb variants such as HbSC Or HbS-thalassemia
 Antenatal diagnosis possible with DNA testing after chorionic villi sampling

20. Management
 Patient education on adequate hydration
 Avoiding excess alcohol
 evidence of splenic involvement -vaccinate against Pneumococcus, Haemophilus
influenzae B and Neisseria meningitides
 Folic acid supplementation
 Blood transfusions with iron chelation
 Hydroxyurea- increased production of HbF- beneficial

21. Management of acute crisis
Acute chest syndrome
 May need Intensive care set up for treatment and monitoring
 Hydration to maintain euvolemia
 Oxygen, noninvasive PPV if necessary
 Bronchodilators –airway reactivity high
 Broad spectrum antibiotics: infection – a common cause of ACS
 Transfusion: both simple & exchange transfusion
 Analgesia- to prevent hypoventilation and atelectasis
 Nitric oxide- in severe cases

22. Mx of acute pain crisis
 Rest, warmth, reassurance, fluid replacement and analgesia.
 Oral analgesics may be sufficient for minor attacks
 Paracetamol/NSAIDs
 Opioids (IM, SC, IV, PO)
 PCA
 Ketamine as adjunct
 Regional blocks as appropriate, epidural use has been reported

23. Common surgical procedures performed in
sickle cell disease patients
 Cholecystectomy
 Splenectomy
 Femoral head reconstruction due to avascular necrosis
 Joint replacement
 Craniotomy due to subarachnoid hemorrhage
 Perioperative mortality has reduced from 10% to 1%.

24. Anaesthetic considerations
PEROP ASSESSMENT
 Patients admitted at least a day prior to surgery
 Day case surgeries???
 A careful history and examination
 to assess disease severity (e.g. hospital admissions, number and timing of
crises) and identify triggers
 LOOK for
signs of fever, dehydration, and vaso-occlusion- elective surgeries postponed
 Assess systems for complications associated with sickle cell disease

25. Investigations
To assess organ dysfunction
 FBC- infection/ acute severe anaemia due to splenic sequestration, marrow
failure or hyperheamolytic crisis/ thrombocytosis
 RFTs- to assess renal involvement
 LFTs and liver enzymes- to asses liver involvement
 S.ALP- elevated in obstructive jaundice with pigmented bile stones
 S.bilirubin- elevated in haemolysis and biliary obstruction
 CXR- pulmonary infarcts/ infection/ features of pul. hypertension./
cardiomegaly

26. Ix’s…….
 Lung function tests- elective major surgeries
 Baseline SPO2
 ABG- elevated methaemoglobin levels would underestimate SPO2
 ECG- cardiac involvement- LVH/RVH/conduction abnormalities
 Clotting profile

27. Preop optimisation
 Minimize fasting period with preoperative hydration to reduce vaso-occlusive
episodes- clear fluids up to 2hours of the surgery
 Preoperative chest physiotherapy
 Preoperative anxiolytics- patients are more anxious
- risk of respiratory depression and hypoxia and
sickling- caution with opiods

28. Transfusion trigger pre-op
 Intraop anaemia -associated with higher vaso-occlusive episodes and higher
mortality
 Traditional transfusion Target- HbS< 30%
 Associated with higher incidence of transfusion related problems
 Current trend- simple target Hb of 10g/dl
 High risk cases- haematology opinion regarding transfusion policy

29. Intraoperative management
 Aseptic method with antibiotic prophylaxis- higher risk of infection
 Mode of anaesthesia
- GA and regional blocks( no method is superior)
- Regional
 Peripheral vasodilatation and increased blood flow is advantageous in preventing
sickling
 Analgesia- intra and post op and in priaprism/acute pain crisis
 No need of airway intervention (higher chance of difficult airway in case of GA)
 Hypotension needing vasoconstrictors may lead to poor peripheral blood flow
 Use of adrenaline with local anesthetics should be avoided

30. GA
 Preoxygenation
 Carefully titrated induction- avoid hypotension
 Controlled ventilation to maintain oxygenation and avoid respiratory acidosis
 Meticulous fluid balance- UOP monitoring or CVP guided individualized, goal
directed fluid therapy in indicated cases
 Avoidance of hypothermia- temperature monitoring/ warm fluids/ warming
blankets/ ambient theater temperature
 Prevent venous stasis-positioning/ avoiding caval compression/ avoiding prone
position/ being cautious when positioning pregnant patients

31. Use of tourniquets
 Controversial regarding the use of tourniquet
 hypoxia/hypoperfusion/acidosis and hypothermia may increase sickling
 If limb completely exsanguinated prior to tourniquet inflation- safer in traits
( shown by small,retrospective studies)

32. Analgesia
Multimodal analgesia should be provided.
 Paracetamol
 NSAIDs- avoid in renal dysfunction
 opioids- patients may be tolerant needing higher doses
 Regional blocks

33. Monitoring
 Standard AAGBI monitoring+ temperature+UOP monitoring
 CVP guided fluid therapy in longer cases

34. Post-operative care
 Extubate when paralysis fully reversed- use of a neuromuscular monitor
 Extended period of monitoring
 HDU set up
 Supplementary oxygen
 Nasopharyngeal airways in patients with severe OSA or following upper air
way surgery
 Adequate analgesia
 Maintain hydration and normothermia
 DVT prophylaxis
 Monitor for acute chest syndrome/ acute vaso-occlusive crisis/stroke

35. HbS variants and anaesthesia
Sickle cell traits(HbSA phenotype)
 Sickling under physiologic conditions- rare
 No need of perioperative blood transfusions
 Maintenance of blood pressure/hydration/ normothermia/adequate analgesia

36. HbSC/ HbS-Thalassemia variants
 HbSC anaemia-Have both HbS and HbC( glutamate in HbA is replaced by
lycine)
 HbS-thalassemia- HbS present in thalassemic patients
 Less severe veno-occlusive episodes
 Perioperative blood transfusion has been shown to be beneficial in abdominal
surgeries
 Other precautions should be taken to prevent veno-occlusive episodes

37. Other facts about sickle cell disease………
 Median age at death - 42 years for men and 48 years for women
 Use of hydroxyurea- promotes HbF production in sickle cell disease patients has
been found to reduce acute crises
 L-glutamine is approved by FDA for children below 5 years to reduce complications
of the disease
 Bone marrow transplant and gene therapy are the only current cures for the
disease
 Sickle cell traits are protected from Plamodium falciparum malariae. Postulated???

38. Summary
 Sickle cell disease is a common genetic disorder
 Patients with sickle cell disease are at a higher risk of needing specific surgeries due to the
disease and morbidity and mortality following these are high
 Veno-occlusive episodes are characteristic of the disease and precipitated by hypoxia,
acidosis, dehydration and hypothermia which are common in peri-operative period
 All precautions should be taken perioperatively to avoid veno-occlusive episodes
( acute pain crisis), acute chest syndrome and strokes
 No mode of anaesthesia is superior in a patient with the sickle cell disease
 Aneasthetists will be sought in intensive care management of sickle cell complications,
provision of analgesia in acute pain crises and anesthetic management of sickle cell disease
patients coming for surgeries.

39. References
 ANAESTHETIC MANAGEMENT OF SICKLE CELL DISEASE IN CHILDREN,
ANAESTHESIA TUTORIAL OF THE WEEK 153.2009
 Goodwin S.R. Sickle Cell and Anesthesia.
 Firth, P.G. Sickle cell disease and anesthesia. Anesthesiology. 2004. 101(3):
p.766-85.
 Firth P. G. Anaesthesia for peculiar cells—a century of sickle cell disease.
British Journal of Anaesthesia 95 (3): 287–99 (2005)
 Wilson M. Haemoglobinopathy and sickle cell disease. Continuing Education in
Anaesthesia, Critical Care & Pain j .Volume 10 Number 1 2010
 Henderson K. Sickle cell disease and anaesthesia. update in anaesthesia.
2014

40. Final FCRA SAQ-2007-mock
 Outline the management of a patient with sickle cell disease undergoing an
appendicectomy.
 Sickle cell anaemia types? Anaesthetic goals?