Keywords
sickle cell disease - cardiopulmonary bypass - endocarditis - sickle crisis - hemofiltration
Introduction
Homozygous sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy
generating hemoglobin SS (HbS). The prevalence is 5% of the world population with
the highest frequency in India, Middle East, South Europe, and among Afro-Caribbean
population.[1] Hypothermia, hypoxia, acidosis, or low-flow states are conditions causing deformation
to the characteristic sickle shape, increasing the risk of hemolysis, vaso-occlusion
and subsequent end-organ damage.[2] Cardiopulmonary bypass (CPB) use in multimorbide patients carries an increased risk
of a sickling crisis requiring special perioperative management.
Case Description
A 45-year-old black African man treated with hydroxycarbamid due to SCD (HbS 96%:
electrophoresis 1 year prior to admission) was hospitalized because of a catheter-related,
coagulase-negative staphylococcal (Staphylococcus epidermidis) sepsis and infection-induced sickle crisis. His medical history was significant
for multiple sickle crises including GAVE (gastric antral vascular ectasia)-syndrome,
portal hypertension, transfusion acquired HCV (hepatitis C virus) infection, and chronic
ulcer of the lateral malleolus. After catheter explantation, an antimicrobial therapy
with daptomycin was initiated after reviewing the resistance profile (oxacillin, ciproxin,
gentamycin) and weighing the pros and cons of the medication related to the patient's
health status and renal function. Because of the growth of multiresistant pseudomonas
aeruginosa in tracheal secretions, therapy with meropenem was added 4 days later.
Due to the sickle crisis and Hb of 7.0 g/dL, initial treatment included hydration
with a transfusion of six red blood cell units (RBCs). During the first days of treatment,
the patient developed acute kidney injury and cardiac decompensation. Echocardiography
demonstrated a bicuspid aortic valve with a vegetation attached to the raphe between
left- and noncoronary cusp accompanied by severe regurgitation. Further findings included
significant right ventricle (RV) dilatation with severe tricuspid regurgitation, pulmonary
hypertension (RV/RA (right atrium)-gradient 41 mm Hg) and a left ventricular ejection
fraction of 54%. After the diagnosis of active endocarditis, the antimicrobial therapy
was changed from daptomycin to vancomycin, still accompanied with meropenem for the
resistant pseudomonas. The preoperative therapy included positive inotropic support
and continuous hemodiafiltration due to acute renal failure and metabolic acidosis.
Additional transfusion of two RBCs before surgery reduced HbS to 5.4%.
Anesthesia was induced with propofol, ketamine, fentanyl, and rocuronium and was maintained
with sevoflurane and remifentanil. During CPB, sevoflurane was replaced with propofol.
Ventilation was controlled with a mixture of air and oxygen (FiO2 = 0.6) and the end tidal carbon dioxide concentration was maintained between 4.0
and 5.0 kPa. The double-valve procedure was performed through median sternotomy with
a routine aortic and bicaval cannulation. A heparin-coated open bypass circuit (Carmeda
Medical Tubing, Medtronic, Brooklyn Park, Minnesota, United States), a hard-shell
venous reservoir, a hollow fiber membrane oxygenator (Affinity Fusion with Carmeda
Bioactive Surface, Medtronic, Brooklyn Park) with integrated polyester arterial line
filter (40 mm pore size), and an arterial roller pump (Stockert S5, Sorin Group, Germany)
were installed. Standard CPB priming was used, consisting of Ringer's lactate, heparine,
tranexamic, acid and mannitol. Because of antithrombin III deficiency, 1,000 U of
antithrombin and three RBCs were added. The flow rate was kept high at approximately
120% (100% = 4.49 Lpm) to maintain venous oxygen saturations between 80 and 85%. Anticoagulation
was performed according to standard protocol (heparine 300 U/kg, ACT [anti-clotting
time] > 350 seconds). Perfusion pressure was kept above 70 mm Hg. Crystalloid cardioplegia
was applied and aspirated immediately through sinus coronarius. Normothermia was maintained
throughout the operation. During continous ultrafiltration to counteract hemodilution,
the uncoated hemofilter (BC140 plus, Maquet Cardiopulmonary GmbH, Rastatt, Germany)
had to be exchanged twice because of coagulation. After resection of the vegetation,
the aortic valve was replaced (25 mm porcine prosthesis, Mosaic Ultra, Medtronic).
The ventriculoarterial portion was reconstructed with a pericardial patch ([Fig. 1a] and [b]). Dilated tricuspid annulus was reconstructed with a 32 mm Tri-Ad Adams tricuspid
annuloplasty ring (Medtronic). After 92 minutes of aortic clamping and 20 minutes
of reperfusion the patient was weaned from CPB easily. Exsanguinated blood in the
oxygenator was discarded and not transfused. Additional eight RBCs were administrated
peripherally through level 1 infuser without pressure. Intraoperative coagulation
was optimized in accordance to thromboelastography with 2 × 250 mL single donor thrombocytes
and four fresh frozen plasma. Negative-balance hemofiltration was continued after
surgery to remove excessive fluid loading and to reverse high potassium. No autologous
cell-saver was used. ([Table 1]: perioperative SCD-checklist)
Table 1
Checklist for perioperative management of SCD under CPB
|
Hb level
|
Body temperature and venous stasis
|
Volemic status
|
Oxygenation/acidosis
|
Cardioplegia
|
|
Preoperative treatment
|
Simple blood transfusion, Hbs < 5% for cardiac surgery (< 30% for major surgery)
|
Active warming during induction with FAWs
|
Normovolemia with perioperative fluid balance
|
Balanced metabolic status, use of hemofiltration when needed
|
–
|
|
Intraoperative management
|
Blood for circuit priming, avoidance of pressure use during peripheral administration
of RBCs, avoidance of cell-saver and retransfusion of exsanguinated blood from the
oxygenator
|
When proceeding in normothermia: active warming with FAWs, underbody conductive heat
mat, circulating water mattress, or radiant warmer; Avoidance of tourniquets and compression
|
Normovolemia with a use of simple transfusion, ultrafiltration and hemofiltration
when needed
|
Hemofiltration during CPB, buffers when needed, Higher flow rate (120%) to maintain
venous oxygen saturations between 80 and 85%, perfusion pressure was kept above 70 mm
Hg
|
Crystalloid cardioplegia, aspiration through sinus coronarius, continuous hemofiltration
during CPB
|
|
Postoperative treatment
|
According to clinical manifestations (i.e., additional transfusions)
|
Active warming with FAWs, positioning on ICU
|
Negative-balance hemofiltration to remove excessive fluid loading
|
Balanced metabolic status, use of hemofiltration when needed, pulse oximetry monitoring:
keep saturation > 95%
|
–
|
Abbreviations: CPB, cardiopulmonary bypass; FAWs, frequent measured and forced air
warmers; Hb, hemoglobin; ICU, intensive care unit; RBCs, red blood, cells; SCD, sickle
cell disease.
Fig. 1 (a) Aortic annulus after patch reconstruction of the ventriculoarterial portion (*);
(b) the epicardium shows structural rough bearings of the surface.
On ICU, the patient was pharmacologically supported, kept warm with a warming blanket
and extubated 8 hours postoperatively. Supplemental oxygen was given to keep oxygen
saturation > 95%. Gentamycin was added at the day of operation but the blood samples
were repeatedly tested to be resistant and finally gentamycin was terminated after
3 days. Rifampicin was initiated at the postoperative day 3. Same day, meropenem was
stopped and vancomycin was changed to Daptomycin after receiving negative samples
of the explanted tissue and native valve with respect to the clinical status and renal
function of the patient.
The hemodiafiltration was stopped 10 days after the surgery. The patient was discharged
after 13 days postoperatively. Three months of follow-up demonstrated correct valve
function and significant improvement of the clinical condition.
Discussion
Although SCD is an unusual hemoglobinopathy in the European population, it gains a
growing importance due to the global migration process. Perioperative management should
minimize potential sickling agents that may lead to deformation resulting in anemia,
small-vessel occlusion, and organ damage.[2]
[3]
[4]
General hematologists' advice includes a reduction of the HbS level to an average
of 5% before or at the time of cardiac surgery.[4] The available methods include homologous transfusion, autotransfusion and partial
exchange. Exchange transfusions do not alter the hematocrit or viscosity but replace
sickle cells with normal erythrocytes and suppress further HbS production. Simple
transfusion expands the normal red cell mass thereby improving oxygen delivery at
the cost of increasing blood viscosity. Autologous transfusion with the use of cell-saver
systems on the one hand, reduce the need for homologous blood transfusion but also
make the filtered blood more prone to sickling.[5] Despite well-known transfusion-related complications, simple blood transfusion seems
to be beneficial also in case of Hb levels > 7 g/dL.[6] Although many clinical reports indicate preoperative exchange transfusion as the
method of choice, there are also cases of successful intraoperative transfusions using
blood for circuit priming.[5]
[6] As discussed in the recent overview of Crawford et al the standard recommendation
on preoperative exchange transfusions is changing by gaining a wider focus on the
negative aspects, that is, association of large volume transfusions and coagulopathy,
culminating free iron, and free radical organ damage. All in all, there is no randomized
study that supports strongly one of both methods. There might be a tendency to a more
conservative transfusion approach targeting a preoperative level > 10 g/dL than a
HbS fraction < 30% reporting similar surgical outcomes.[7] In our anemic patient, pre- and intraoperative transfusions were chosen as the most
adequate option, as the HbS was almost 5% preoperatively after having received cumulatively
eight RBCs over a time period of 12 days because of decreasing Hb levels due to infectious
status.
In view of vasoconstriction, normothermia was described as the most frequent option.[5]
There is, however, evidence that hypothermia appears in vitro to slow polymerization
of HbS and delay the sickling of the RBCs.[5] Few papers report intraoperative hypothermia as a successful method in SCD patients
undergoing CPB.[8] In our patient with acute renal injury and chronic malleolus ulcer, we chose normothermia
to avoid vasoconstriction and sequential complications.
Focusing on cardioplegia, described methods include warm blood or crystalloid infusions
and specially designated combinations.[3] Theoretically, crystalloid, cold cardioplegia should be avoided because of the possibility
of sickling and vascular occlusion in the coronary microvasculature. Nevertheless,
no negative effects concerning myocardial infarction or additional inotropic support
during intensive care unit (ICU) stay have been reported.[9] Removal of potassium and cardioplegia can be provided by continuous hemofiltration
and aspiration through the sinus coronarius by the surgeon.
Hypoxia can be successfully avoided using venous oxygen saturation as a reliable oxygenation
marker, with SvO2 levels of 80%.[3]
[5] After extubation pulse oximetry monitoring should be continued to keep saturation > 95%.
Low-flow states, hypovolemia and acidosis can be monitored and avoided with the use
of CPB and continuous hemofiltration.
In summary, CPB can be well tolerated after individual adaptation of the standard
protocol and avoidance of risk factors. The preoperative exchange transfusion does
not appear to be necessary and a simple euvolemic transfusion at the time of operation
can be beneficial in anemic patients. Crystalloid cardioplegia seems to be a safe
method. Multidisciplinary planning, taking into account all risk factors, is required
for a safe and individually adjusted therapy.
