Perioperative management of sickle cell disease

King Abdullah Medical CityDepartment of Anesthesia

Perioperative Management of Sickle Cell Disease Patients

ByMohamed Ahmed

SayedalahlMD Anesthesia & Surgical Intensive

Care

Monday, February 23, 2015

-October 1902, Ohio state university.

-1905 North African Arab subjects.

-1910, James Herrick, detailed case report.

-1927, sickling by deoxygenation & reversed by reoxygenation.

-Clinical hypothesis:

-1955, 1st major review:

One of students noticed elliptical RBCs

Jaundice, dyspnea, LN, dark urine, leg ulcers,

epigastric pain & anemia

deoxygenation→sickling→vasoocclusion→moredeoxygenation→moresickling(vicious circle)

High incidence of perioperative serious and potentially fatal

complications

Hemoglobin Structure

Epidemiology

- Mutant -globin gene → Hereditary hemoglobinopathy → production of variant Hb ( Hb SS) → Sickle cell anemia

- Variations in & Around sickle gene → different haplotypes ( 4 haplotypes in Africa & 1 Arabo-Indian or Asian haplotype in India & Persian gulf region)

- Heterozygous carrier state → SCT

Genetics

The s Mutation

6th Codon of -Globin Gene

GAG

Glutamic

GTG

Valine

Inheritance

-Inherited as Autosomal Co-dominant

Genotypes of Sickle cell disease

- Sickle cell anemia (Homozygous, HB SS)

Sickling occurs at PO2 ˂ 40 mmHg

- Sickle cell trait (Heterozygous, HB AS)

Sickling occurs at PO2 ˂ 20 mmHg

- Sickle-Hemoglobin C disease (HB SC)

- Sickle- β thalassemia disease (HB S β thal)

Gene penetration (heterogenicity)• Genotype differences (sickle cell anemia,

sickle cell trait, sickle cell HB C, sickle cellthalassemia)

• Haplotype differences (African, Arabo-Indian)

• HB synthesis, mutltistep, numerous genes(timing, extent and coordination)

• Extreme variability in HbF production• Polymorphism at cellular level (RBCs

membrane structure & function, hemecatabolic enzymes, nitric oxide generatingsystems & inflammatory mediators.

Molecular biology

1- Absence of the negative charge → instability of oxygenated hemoglobin → denaturation & break → RBCs hemolysis.

2- Hydrophobic amino acid → decrease in solubility of deoxygenated HB → polymerization & precipitation → sickling of RBCs.

Biochemistry

altered NO synthetase, increased leucocytic count,

activated coagulation pathway, increased circulatory cytokines

Vasoocclusion

Historical hypothesis of RBCs sickling:

Role of endothelial and vascular dysfunction:- Survival of patients with SCD + cyanotic HD

- Studies:Effect of hypobaric hypoxia

Effect of inhalation of hypoxic gas mixture (FiO2 10-15%)

- Ascent to high altitudes or long aircraft flights

Clinical Picture

Progressive organ damage , intermittent periodsof severe pain & pulmonary complications

Severity and progression → markedly variable:Relatively benign course Early organ dysfunction and death

Pulmonary & Neurological complications

Chronic renal failure

Many deaths not attributed to chronic organ failure acute episode of pain, respiratory compromise, stroke

Clinical Picture

Clinical Picture…cont

Pain crises or VOC:

Most common sites: lumbar spine (49%), abdomen (32%),

femoral shaft (30%), and knee (21%)

Triggering events: without cause (˃50%), perceived skin

cooling (34%), emotional stress (10%), physical exertion (7%), and alcohol consumption (4%)

Arise from cortical infarction or from marrow infarction

Abdominal pain: bowel dysfunction, organ infarction, referred

from the ribs

Clinical Picture…cont

The acute chest syndrome (ACS):acute pneumonia like, new pulmonary infiltrate involving at leastone complete lung segment, but excluding atelectasis.

Additional diagnostic feature: chest pain, pyrexia greater than38.5°C, tachypnea, wheezing, & cough.

Precipitants: infectious pathogens, fat embolism after bone

marrow infarction, pulmonary infarction and surgical procedures.

Chronic progressive lung damage:persistent inflammatory process → lower airway obstruction &airway hyperreactivity → fibrosis and a progressive restrictivedisease → pulmonary hypertension, and right-sided cardiachypertrophy & and severe hypoxemia.

Clinical Picture…cont

-Neurological: (stroke)

Infarctive : in adolescence, intimal hyperplasia.

Hemorrhagic : third decade of life, rupture of chronically damaged arteries.

Renal: (Nephropathy)

Papillary necrosis → painful gross hematuria

Glomerular lesions → proteinuria

Hyposthenuria → specific gravity ˂1010

Chronic renal failure → third or fourth decade

Perioperative Epidemiology

Perioperative complications:

SCD-specific complications: Pain crisis and ACS

SCD-related complications:

Erythrocyte alloimmunization and transfusion reactions

Nonspecific complications:, bleeding, infection , fever, thrombosis, embolism, and death from causes other than SCD.

Preoperative Assessment

- Determine the risk of perioperative SCDcomplications

- Most frequent procedures: cholecystectomy,splenectomy, dilation and curettage, caesareansection, hysterectomy, adenotosillectomy,myringotomy and orthopedic prosthetic surgery.

- Incidence of complications: 3% for orthopedicsurgery, 8% for non-obstetrical intraabdominalsurgery, 17% for caesarean section andhysterectomy.

Predictors of Postoperative Complications

Preoperative Investigations

Perioperative Management

Erythrocyte Transfusion

Indications: prevention or treatment.

Rationale: dilution of sickle cells.

Studies:

Transfusion Vs Nontransfusion

Aggressive Vs Conservative

CPB and craniotomies

Alloimmunization: Non-ABO AB against Rh, Kell, & Lewis, 8-50% in SCD, causes.

Perioperative ManagementProphylactic erythrocyte transfusion remains a treatment with many complications.

Lack of clinical guidelines.

The National Heart, Lung, and Blood Institute (NHLBI)

SCD perioperative management Guideline.doc

Intraoperative Management

Improvement of Oxygen Delivery

Oxygen delivery impaired: obstructive or restrictive lung disease, vascular damage, abnormal rheology, peripheral A-V shunting ↑NO scavenging.

Compensatory mechanisms: ↑MV, ↑cardiac SV, ↓ PVR, ↑2,3- DG, and ↓Hct, and ↑ NO production.

Induced hypotension & autologous transfusion

Intraoperative ManagementOxygenation-Hypoxia as a precipitant of perioperative SCD-specific complications.

Prolonged O2 supplementation:-Suppression of erythrogenesis.-Withdrawal → VOC.

Little rationale:-Avoidance of preoperative anxiolytic medication.-Intraoperative hyperoxygenation.-Prolonged postoperative O2 supplementation.

Maintenance of adequate oxygenation

Intraoperative Management

Hydration

- Dehydration as a cause of perioperative complications.

- Adequate hydration.

- Modification of fluid management .

Intraoperative Management

Thermoregulation-Hypothermia as a precipitant of SCD complications

-Hyperthermia (SCT)

-Maintenance of normothermia.

Acid-base Regulation-Acidosis accelerates erythrocyte deformation.

-Alkalinization is not effective .

-Maintenance of normal acid-base balance.

Intraoperative Management

-Anesthetic technique

-GA Vs. RA

-Epidural anesthesia or Analgesia:

Pain control

VD

Oxygenation

-Avoid or minimize tourniquet

Postoperative Management- Oxygen supplementation.

- Adequate hydration.

- Aggressive pain management.

- Incentive spirometry.

- Early ambulation.

- Consider daily CBC, platelet and reticulocyte.

Postoperative ManagementPain Crisis

- Analgesia: Opioids: morphine, PCA, Fentanylpatch, Pethidine, (tolerance), NSAID, Corticosteroids,Epidural analgesia

- Incentive spirometry

- Supplemental oxygen

- Adequate hydration

- Erythrocyte & plasma transfusion.

- ACS, precipitated by pain crisis.

- psychological distress.

Postoperative Management

Acute Chest Syndrome

- 3 days after surgery and lasted 8 days

- Early incentive spirometry, bronchodilator therapy, supplemental oxygen, adequate analgesia, and broad-spectrum antibiotics.

- Blood transfusion.

- Nitric oxide and corticosteroids.

- Mechanical ventilation.