Re: MS 80092 for proofreading
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Editorial (Asian Annals) (editorial@asian-annals.org)
Sent: Thursday, August 21, 2008 8:38:25 AM
To:
Khaled Al-Ebrahim (dr.k-e@hotmail.com)
Cardiac Surgery and Sickle Cell Disease
Subject
Dear Dr. Khaled E Al-Ebrahim,
MS#80092 is in line for publciation, it will most probably be published by end of
2008. A gally proof will be sent to you for proof reading in due course before
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Asian Cardiovascular & Thoracic Annals
AA-MS080092 Original Contribution. Subject Code: 1, 35
0 tables/0 figs. Keywords: Anemia, Sickle Cell; Exchange Transfusion, Whole Blood; Heart
Valve Diseases; Heart Valve Prosthesis Implantation.
Running head: Cardiac Surgery and Sickle Cell Disease
Cardiac Surgery and Sickle Cell Disease
Khaled E Al-Ebrahim, FRCSC
Department of Surgery
Faculty of Medicine, King Abdul Aziz University
Jeddah, Saudi Arabia
For reprint information contact:
Khaled E Al-Ebrahim, FRCSC
Tel: 966 2 6401000
Fax: 966 2 6408347
email: Khaled_alebrahim@yahoo. com
Department of Surgery, King Abdulaziz University Hospital, PO Box 80215, Jeddah 21589,
Saudi Arabia.
2
ORIGINAL CONTRIBUTIONS
Cardiac Surgery and Sickle Cell Disease
Khaled E Al-Ebrahim, FRCSC
Department of Surgery, Faculty of Medicine, King Abdul Aziz University, Jeddah, Saudi
Arabia
For reprint information contact: Khaled E Al-Ebrahim, FRCSC Tel: 966 2 640 1000 Fax: 966 2 640 8347 Email:
dr.k-e@hotmail.com, Department of Surgery, King Abdulaziz University Hospital, PO Box 80215, Jeddah
21589, Saudi Arabia.
.
Abstract
Three patients with homozygous sickle cell disease underwent successful open heart surgery
for multivalvular lesions. Details of the surgical technique and the necessary precautions are
described. Exchange transfusion was implemented in all cases. Crucial issues in cardiac
surgical management to avoid or at least minimize vasoocclusive crisis and associated
complications are discussed.
(Asian Cardiovasc Thorac Ann 2008;16:xx–xx)
Introduction
Sickle cell disease is one of the most common genetic disorders world- wide, affecting
approximately 8% of black people.1 The prevalence in Saudi Arabia has not been studied.
Sickle cell anemia is an inherited disease in which the red blood cells, normally disc-shaped,
become crescent-shaped, causing small blood clots that give rise to recurrent episodes of
sickle cell pain or vasoocclusive crisis. Complications of sickle cell disease include recurrent
aplastic and hemolytic anemia, gallstones, multisystem disease (kidney, liver, lung), narcotic
abuse, splenic sequestration syndrome, acute chest syndrome, erectile dysfunction (as a result
of priapism), blindness/visual impairment, neurologic symptoms and stroke, joint destruction,
and infections including pneumonia, cholecystitis, osteomyelitis, and urinary tract infection.2,3
As surgery in general, and especially cardiac surgery, in homozygous patients is associated
with high morbidity and mortality, special care and specific precautions are required
perioperatively to minimize the surgical risk.
Case Reports
Three patients with sickle cell disease underwent open heart surgery for multivalvular lesions.
The details are as follows.
CASE 1
An 18-year-old Chadian male, known to have sickle cell disease (80% sickling by hemoglobin
electrophoresis) with renal impairment and rheumatic heart disease, was admitted with
abdominal pain, dyspnea, recurrent fever and chills. On examination, his temperature was
38.5°C, heart rate 110 beats/min, blood pressure 100/60 mm Hg, and he was in normal sinus
rhythm. Auscultation revealed a visible laterally displaced apex beat, pansystolic mitral
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murmur, and an early diastolic aortic murmur. His hemoglobin (Hb) level was 7.5 g/dL, white
cell count 19 × 103/μL, urea 34 μmol, creatinine 369 μmol, total bilirubin 130 μmol, and
indirect bilirubin 90 μmol. He was admitted to the intensive care unit where echocardiography
showed dilated cardiac chambers, severe mitral and aortic regurgitation, moderate pulmonary
regurgitation, and pulmonary hypertension. His left ventricular ejection fraction was only
30%. Blood was sent for culture, and he was started on empiric antibiotics: ceftriaxone,
erythromycin, and ampicillin. The following day, he developed convulsions and was intubated
and mechanically ventilated. Computed tomography of the brain showed a suspicious area of
hypodensity in the right periventricular white matter region. The patient improved gradually
and was extubated. Blood cultures grew staphylococcus epidermidis (coagulase-negative) and
he received a 6-week course of intravenous antibiotics. He was discharged and readmitted for
valve replacement. Mechanical aortic and mitral valves were implanted. All perioperative
sickle cell precautions were undertaken. The postoperative course was smooth. The patient
was started on anticoagulation, mobilized, and discharged home well.
CASE 2
A 28-year-old male originally from south Saudi Arabia, known to have sickle cell disease,
rheumatic heart disease, severe mitral and aortic regurgitation, was admitted for recurrent
attacks of shortness of breath on moderate exertion. Cardiac examination revealed a muffled
1st heart sound, normal 2nd heart sound, a pansystolic murmur over the apex radiating to the
axilla, and an early diastolic murmur over the aortic area. There was no lower limb edema.
His Hb level was 7.5 g/dL. Urea and electrolyte levels were normal. An electrocardiogram
showed normal sinus rhythm and left ventricular dilatation. Echocardiography revealed severe
aortic insufficiency, moderate to severe mitral insufficiency, left ventricular dysfunction,
moderate to severe pulmonary hypertension, and an ejection fraction of 60%. The patient
underwent aortic and mitral valve replacement using tissue valves (aortic valve size 21 mm,
mitral valve size 27 mm). He had a smooth intra- and postoperative course. Cardiac
rehabilitation and temporary anticoagulation were started. Postoperative echocardiography
showed both valves were functioning well, with no paravalvular leak or dehiscence, mild to
moderate left ventricular dysfunction, and an ejection fraction of 50%. He was discharged
home in good condition with clinical follow-up. During more than 1 year of follow-up, he has
shown steady improvement.
CASE 3
A 14-year-old Sudanese girl with sickle cell disease (> 80% sickling on Hb electrophoresis),
rheumatic heart disease with mainly severe mitral and tricuspid regurgitation, pulmonary
hypertension, and old treated tuberculosis, presented to the emergency room with bilateral
lower limb edema for 3 days, associated with shortness of breath at rest and orthopnea. On
examination, she was jaundiced with multiple cervical lymph nodes, and her jugular venous
pressure was 7–8 cm H2O, with hyperdynamic circulation, a regular pulse, normal 1st heart
sound, loud 2nd heart sound, and a pansystolic murmur at the mitral and tricuspid area.
Abdominal examination revealed hepatomegaly and ascites. She was started on diuretics and
digoxin. During hospitalization, she went into fast atrial fibrillation which was controlled with
amiodarone. Ecchocardiography showed severe mitral and tricuspid regurgitation with left
ventricular and bi-atrial dilatation She underwent mitral and tricuspid valve repair using
flexible annuloplasty rings (30 mm for the mitral valve, 32 mm for the tricuspid valve). Her
postoperative course was smooth and she was discharged home in good condition.
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In all patients, general anesthesia was induced with etomidate, fentanyl, midazolam, and
pancuronium. It was maintained with isoflurane, oxygen, and nitrous oxide. Cardiopulmonary
bypass was instituted using a membrane oxygenator, cardiotomy reservoir, regular filters,
hemofilters, and a tubing set. The circuit was primed with Ringer’s lactate solution containing
5% dextrose, 8.4% sodium bicarbonate, and 1 unit of blood. Heparinization was achieved
with 300 units/kg. Normothermic bypass was conducted using aortic and bicaval cannulas.
Cardiac arrest was achieved with hypothermic blood cardioplegia. All patients underwent a
30% exchange transfusion and continuous hemofiltration during cardiopulmonary bypass. Hb
levels were maintained at 6–8.5 g/dL, with a hematocrit of 18%–28%. Each of the 3 patients
had a different valve procedure. The first received 2 ATS Medical mechanical valves (ATS
Medical, Inc., Minneapolis MN, USA), in view of their proven low thrombogenicity, as both
the mitral and aortic valve had been destroyed by endocarditis, and to avoid the calcification
of bioprostheses usually associated with renal failure. The mitral valve was approached
through the interatrial groove. The second patient received 2 St. Jude Medical Biocor
bioprostheses (St. Jude Medical. Inc., St. Paul, MN, US) to avoid the controversial issue of
prosthetic valve-associated hemolysis.6 In the 3rd patient, fortunately both mitral and aortic
valves were amenable to repair using annuloplasty rings. All 3 patients were weaned off
cardiopulmonary bypass without difficulty.
Discussion
Sickle cell anemia affects millions throughout the world. It is particularly common among
people whose ancestors come from sub-Saharan Africa, South America, Cuba, Central
America, Saudi Arabia, India, Turkey, Greece, and Italy. Hemoglobin S results from a single
base mutation in beta chain of hemoglobin, the adenine base is replaced by thymine, so
glutamic acid is replaced by valine. The sickling test and hemoglobin electrophoresis help in
diagnosis and differentiate homozygous from heterozygous types. A homozygous patient will
have 80%–90% HbS, 2%–20% HbF, and 2%–4% HbA2. A carrier will have 35%–40% HbS
and 60%–65% HbA. The test is not accurate in a person who has recently received a blood
transfusion.3 Common clinical symptoms include paleness, yellow eyes/skin, fatigue,
breathlessness, rapid heart rate, and delayed growth and puberty. Sickling may be induced by
hypoxia, hypothermia, acidosis, vascular stasis, or hypovolemia. The purpose of therapy is to
manage and control symptoms and limit the frequency of vasoocclusive crises. During a sickle
cell crisis, painful episodes are treated with analgesics and adequate liquid intake.
Hydroxyurea was found to help some patients by reducing the frequency of painful crises and
episodes of acute chest syndrome, and decreasing the need for blood transfusions. Antibiotics
and vaccines are given to prevent bacterial infections which are common in such children.
The risk of an intraoperative crisis due to sickle cell disease is the major consideration in
cardiovascular surgery. It is well documented that low oxygen tension and acidosis can induce
sickling in patients on cardiopulmonary bypass; because the artificial circulation is wholly
controlled by the perfusionist, this may trigger a crisis of profound magnitude. It is generally
agreed that avoidance of acidosis, maintenance of adequate blood flow and oxygen tension
during cardiopulmonary bypass, and close monitoring of laboratory results are essential in the
management of sickle cell patients.4–7 These issues have to be very well understood by the
perfusionist, anesthesiologist, and the surgical team, because a violation may increase the
surgical risk and jeopardize the patient’s life. Continuous online arterial oxygen tension, acidbase balance, and temperature control are essential. Intra- and postoperative control of
hemodynamic parameters, regular checking of the hematocrit to keep it at 20%–30%,
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electrolytes, blood gases, avoidance or minimization of postoperative pain are important in
these patients. Although, it is preferable to avoid hypothermia which will cause
vasoconstriction, a number of studies have employed mild to moderate cooling without
adverse effects.7,8 Reviewing the literature and our own cases, we found that normothermic
bypass, allowing the temperature to drift, and using only cold cardioplegia at 4°C were the
safest options, especially when operating on high-risk and large numbers of cases.4–6,9–12
Warm blood cardioplegia, with its high potassium concentration, may have a deleterious
effect on patients with impaired renal function
Pre- or intraoperative partial exchange transfusion have been recommended and implemented
in the majority of cardiac patients to reduce the percentage of HbS.6,7,9,10 At least 30% of the
circulating plasma volume is sequestered to improve the quality of the perfusate, increase
oxygen delivery, and decrease the risk of a sickle cell crisis during bypass. In a few case
reports, exchange transfusion was not implemented.5,8 In our cases, exchange transfusion was
performed once intraoperatively after cannulating and before going on bypass. The
perfusionist drained 500–1,000 mL of blood from the venous reservoir, depending on the
patient’s body weight, and replaced it with 1–2 units of packed red blood cells. Hemofiltration
increases hematocrit, platelet count, and clotting factors, helps potassium removal, reduces
complement activation, removes extracellular water, and helps in avoiding acidosis. There are
several reports of favorable but sometimes variable effects of hemofiltration, especially in
pediatric patients.6,7,13–15 Valve repair remains the procedure of choice to avoid prosthetic
valve-related complications, especially hemolysis, anticoagulant use, and infection.5–8,11
Several reports record no preference for tissue valves over mechanical valves.4,5,7,8,12 Others
stipulated that mechanical valves should be avoided to minimize the risk of hemolysis which
may induce a crisis in sickle cell patients.6 Given the shorter life expectancy of these patients
and the risks of mechanical valve hemolysis, bioprosthesis calcification, and reoperation, we
prefer to use mechanical valves for patients < 30-years old with non-repairable valves, and
biological valves for older patients. Postoperative pain management is helped by giving
multiple analgesia. Prophylactic antibiotic therapy is important to minimize the risk of
infection.
These 3 cases underwent different valve procedures, which emphasizes the tolerance of these
patients provided the body environment during and after surgery is suitable and does not
trigger vasospasm. Four other patients with the heterozygous form (sickle cell trait) also
underwent valve procedures by the author in another institution, without any problems; these
were not as critical as the homozygous cases. The world literature is deficient, with no major
scientific contribution to help this subset of cardiac surgery patients, except for sporadic cases,
mostly reported more than a decade ago.
References
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Wintrobe MM. Clinical hematology. Philadelphia: Lea & Febiger, 1993:1064.
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