Exchange transfusion through the heart-lung machine in a sickle cell disease patient undergoing aortic valve replacement: proposition for a pragmatic protocol

Abstract

Background

In sickle cell patients scheduled for cardiac surgery, preoperative decrease in hemoglobin S (HbS) by exchange transfusion is advocated; however, protocol may vary according to institution. In this report, we provide a standardized framework that allow to perform an intraoperative tailored exchange-transfusion directly through the heart-lung machine.

Case Report

A 74-year-old male patient, with a SC genotype sickle cell disease (preoperative HbS at 51%), underwent bioprosthetic aortic valve replacement. The required volume for exchange transfusion was calculated to obtain an HbS level at 30%. The exchange transfusion was performed directly through cardiopulmonary bypass (CPB) circuit. Surgery was conducted in normothermia, with warm blood cardioplegia, high flow rates, and careful monitoring of oxygenation and pH level. Surgery and postoperative care were uneventful, allowing complete discharge from intensive care unit (ICU) at day two.

Conclusion

A standardized exchange transfusion protocol directly through the CPB circuit allow to confidently decrease HbS to the targeted value just prior surgery.

Keywords

sickle-cell disease anesthesia hemoglobin S exchange transfusion cardiopulmonary bypass red blood cells

Introduction

Sickle cell disease (SCD) is an autosomal recessive disease characterized by an excessive synthesis of an abnormal hemoglobin chain, the hemoglobin S (HbS), leading to sickle-shape red blood cells that may cause ischemic injury.¹ Cardiac surgery especially under cardiopulmonary bypass (CPB) is at high risk of sickle cells crisis by combining multiple triggers of HbS polymerization. To date, there isn’t any specific recommendations on how to manage such patient and to perform exchange-transfusion prior to surgery.² Only few case series or report are available and recommend targeting a HbS ≤ 30% prior to surgery. In this case report we aimed to specifically address the management of exchange-transfusion directly through the CPB circuit and to provide a standardized calculation protocol to determine the volume of blood replacement needed to target a HbS level below 30%.

Case presentation

Anaesthetic consideration

A 74-year-old male (180 cm and 70 kg), with a medical history of hypertension, chronic kidneys failure (clearance CKD-EPI: 52 ml/min/1.73 m²) and SCD (SC genotype) was scheduled to bioprosthetic aortic valve replacement for severe regurgitation. Preoperative and postoperative characteristics and biology are summarized in Table 1. General anesthesia was provided by intravenous injection of 1 mg midazolam, 0.3 µg/kg sufentanil, 0.3 mg/kg ketamine, and 0.3 mg/kg etomidate then maintained by continuous intravenous administration of propofol and sufentanil at target concentrations infusion. Neuromuscular blockade was obtained by atracurium. 20 000 UI of heparin were given intravenously for an activated clotting time > 450 s prior to cannulation.

Table 1.

Patient characteristic, preoperative and intraoperative data.

Variables	Patient
Demographic characteristics
Age (years)	74
Weight (kg)	70
Body Mass index (kg/m²)	21,6
EuroSCORE II (%)	3.8
Left ventricular ejection fraction (%)	60
Intraoperative data
Time of CPB (min)	72
Time of aortic cross clamping (min)	56
Intraoperative crystalloids (ml)^a	1100
Red blood cells (ml)	838
Biology	Preoperative	Intraoperative (CPB)	Postoperative ^b
Hematocrit (%)	30	25	27
Hemoglobin (g/dl)	10.5	9.0	9.7
HbS (%)	51.4	32.8	34.4
HbC (%)	45.1	28.6	30.4
HbA1 (%)	0	35	31.8
HbA2 (%)	3.5	3.2	3
Prothrombin time (%)	80	NA	92
Fibrinogen (g/l)	2.8	NA	1.6
GFR (CKD-EPI) (ml/min/1.73 m²)	52	NA	50.6
Free Hb concentration (mg/dl)	NA	13	<10

CPB: cardiopulmonary bypass. GFR: glomerular filtration rate. Hb: hemoglobin.

^aIncludes CPB priming. NA = not available.

^bDay one.

Perfusion management

CPB was established with a nonpulsatile centrifugal pump (Essenz^TM Perfusion System, Livanova^TM, Eastbourne Terrace London, England W2 6LG). The circuit consisted of 3/8-inch polyethylene tubing (LivaNova^TM, Mirandola, Italy), an Inspire 6F microporous polypropylene membrane (oxygenator, Livanova^TM, Eastbourne Terrace London, England W2 6LG). Cannulation was made in the aorta with a 20 Fr arterial cannula (Medtronic, Minneapolis MN, United States) and in the right atrium/inferior vena cava with a 29/37 Fr cannula (LivaNova^TM, Arvada CO, United States). Warm blood cardioplegia in the aortic root was initiated following aortic cross clamping and repeated every 15 min. Flow was maintained above 2.4 l/min/m², F_mO₂ above 70% and a pH between 7.38–7.42. Total duration of aortic cross clamping and CPB was 56 and 72 min respectively. CPB weaning was uneventful. Of note, we did not use an autologous cell salvage device.

Protocol for exchange-transfusion (Annex 1)

Exchange transfusion to target a HbS level ≤ 30% was achieved in the operating room directly through the CPB circuit. The process to determine the volume of blood that would have been replaced is presented below:

Total patient’s blood volume is:

V_{b l o o d p a t i e n t} = k \times W = 70 \times 70 = 4900 m L

(1)

where k = 70 ml/kg (65 if female) and W = weight (kg).

Patient’s red blood cell volume is:

V_{R B C p a t i e n t} {= V}_{b l o o d p a t i e n t} \times {H c t}_{0} = 4900 \times 0, 30 = 1470 m L

(2)

where Hct₀ represent the preoperative patient haematocrit. Each fraction of Hb (A₁, A₂, S, C) depends on the total volume of red blood cells (RBC) remaining in the patient after exchange-transfusion. The volume of RBC to withdraw according to the targeted fraction of HbS may be approached as following:

f_{t a r g e t e d H b S} = f_{p a t i e n t H b S} \times \frac{{V_{R B C p a t i e n t} - V}_{R B C t o w i t h d r a w}}{V_{R B C p a t i e n t}} + f_{t r a n s f u s e d H b S} \times \frac{V_{R B C p r i m i n g}}{V_{R B C p a t i e n t}}

The initial HbS fraction was 51%, and the targeted HbS was 30%. As the blood product transfused contained no HbS, the second part of the equation can be removed:

f_{t a r g e t e d H b S} = f_{p a t i e n t H b S} \times \frac{{V_{R B C p a t i e n t} - V}_{R B C t o w i t h d r a w}}{V_{R B C p a t i e n t}}

(3)

The volume of red blood cells to withdraw and to replace is:

V_{R B C t o w i t h d r a w} = {V_{R B C p a t i e n t} - \frac{f_{p r e d i c t e d H b S}}{f_{p a t i e n t H b S}} \times V_{R B C p a t i e n t} = V}_{R B C p a t i e n t} (1 - \frac{0.30}{0.51}) = 606 m l

(4)

The theoretical volume of total blood to withdraw and replace is

V_{b l o o d t o w i t h d r a w} = \frac{V_{R B C t o w i t h d r a w}}{{H c t}_{0}} = \frac{606}{0, 30} = 2020 m l

(5)

Priming composition was calculated with a ratio 1:1 to replace the 606 ml of RBC to withdraw and to provide a hematocrit close to patient’s initial hematocrit. Priming consisted in: 838 ml of RBC (three blood package unit), 545 ml of fresh frozen plasma and 250 ml of 1.4% sodium bicarbonate for a total volume of 1633 ml.

Assuming that the haematocrit of the blood package is about 0.7, the priming haematocrit is:

{H c t}_{p r i m i n g} = \frac{V_{R B C p r i m i n g}}{V_{p r i m i n g t o t a l}} = \frac{0.7 \times 838}{1633} = 0, 36

(6)

Sequestration of blood was performed through the venous canula prior to CPB initiation. The patient was placed head downward, and the venous blood was passively drained in a bag connected to the shunt line (Figure 1). The flow of the blood exchanged was carefully titrated on patient’s mean arterial pressure (MAP). In first intention, continuous infusion of norepinephrine was used to maintain a MAP above 65 mmHg. If needed, priming volume was slowly infused through the aortic cannula. 1800 ml of total blood was withdrawn, then the CPB was started because the MAP bellowed 60 mmHg. The sequestration process took 5 minutes.

The predicted hematocrit following CPB initiation is:

{H c t}_{C P B} = \frac{V_{R B C C P B}}{V_{t o t a l C P B}} = \frac{V_{R B C p a t i e n t} - V_{w i t h d r a w n} + V_{R B C p r i m i n g}}{V_{b l o o d p a t i e n t} - V_{w i t h d r a w n} + V_{p r i m i n g}} = \frac{1470 - 1800 \times 0.3 + 586}{4900 - 1800 + 1633} = 0.32

(7)

From equation (3) and considering that transfused RBC contain only A1 haemoglobin, the predicted haemoglobin profile of the patient is:

f_{p r e d i c t e d H b} = f_{p a t i e n t H b} \times \frac{{V_{R B C} - V}_{w i t h d r a w n}}{V_{R B C C P B}} + f_{t r a n s f u s e d H b} \times \frac{V_{R B C p r i m i n g}}{V_{R B C C P B}}

f_{p r e d i c t e d H b S} = 0, 51 \times \frac{1470 - 1800 \times 0.3}{1516} + 0 = 0, 31

f_{pr e d i c t e d H b C} = 0, 45 \times \frac{930}{1516} + 0 = 0, 28

f_{p r e d i c t e d H b A 1} = 0 + 1 \times \frac{586}{1516} = 0, 39

f_{p r e d i c t e d H b A 2} = 0, 035 \times \frac{930}{1516} + 0 = 0, 02

Blood sample performed following CPB initiation showed a hematocrit at 25%, a Hb at 9.0 g/dL, a HbS at 32.8%, HbC at 28.6%, HbA₁ at 35%, and HbA₂ at 3.2%. Additional 250 ml of blood was withdrawn, and another RBC unit (275 ml) was administered to target a HbS at 30%.

Postoperative management

Postoperative course was uneventful. Mechanical ventilation was weaned 3 hours postoperatively, biological exams at day one showed a Hb level at 9.7 g/dl and hematocrit at 28%. Analgesia was satisfactory with multimodal analgesia. The patient was discharged from ICU at day 2.

Discussion

In the present report, we propose a pragmatic protocol to determine the volume of blood that need to be withdrawn to lower HbS below 30% before on-pump cardiac surgery. While some teams recommend performing exchange-transfusion the day before the surgery, exchange-transfusion directly in the operating room through the heart-lung machine allows to carefully control the temperature the hemodynamic status of the patient while performing the procedure within few minutes saving time and staff resources. This method of blood sequestration has already been described in sickle cells patients without complications.^3,4 Our mathematical approach allows to accurately determine the volume to withdraw, the priming composition and to predict the concentration of HbS after initiation of CPB with a small error margin. It is particularly useful when exchange-transfusion is performed on the day of surgery as the hemoglobin fraction analysis may take several hours making confirmation of the targeted HbS only retrospective. When perioperative measurement is available (about an hour in our center), it can provide earlier confirmation and help refine the exchange target. Before initiating CPB, 89% (1800/2020 ml) of the targeted blood volume was withdrawn. Due to the fall in MAP, we decided to start CPB and to withdraw the remaining volume while on-pump. Several measures such as putting the head downward, infusing norepinephrine and slow reinfusion of the priming through the aortic canula may help to withdraw large volume of blood while limiting hemodynamic instability. In their report on 47 patients, Yousafzai et al., withdrawn one third to one quarter blood volume through the heart lung machine but without specific protocol.³ Bochierri et al., proposed a complete exchange-transfusion through the heart lung machine to lower HbS below 5%, however, it necessitates large volume of transfused RBC (8 units in their report).⁴ Targeting HbS fraction ≤ 30% seems acceptable, to decrease the risk of intraoperative haemolysis and sickling while limiting RBC transfusion. In our case, the free Hb concentration, a marker of haemolysis, was not increased after surgery.

Conclusion

Exchange-transfusion through the heart lung machine for sickle cell patients undergoing cardiac surgery is easy to set up by using a mathematical approach to predict the volume of blood that need to be exchanged before starting CPB.

Supplemental material

Supplemental Material - Exchange transfusion through the heart-lung machine in a sickle cell disease patient undergoing aortic valve replacement: proposition for a pragmatic protocol

Supplemental material for Exchange transfusion through the heart-lung machine in a sickle cell disease patient undergoing aortic valve replacement: proposition for a pragmatic protocol by Nicolas Mavambu, Baptiste Monnier, Virginie Louvain Quintard, Charbel Zaccour, Jacques Thès, Sylvain Diop in Perfusion

Footnotes

Acknowledgement

We want to thank all the members of our perfusion team, for their work and day to day commitment.

ORCID iDs

Nicolas Mavambu

Sylvain Diop

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available on request to the corresponding author.

Author contributions

NM wrote the first draft of the manuscript. SD, BM, VLQ, CZ and JT reviewed it critically and made some substantial corrections. All authors approved the final version of the manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Financial/Non-financial disclosure: Support was provided solely from institutional and/or departmental sources.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data underlying this article will be shared on request to the corresponding author.*

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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