Asian Cardiovasc Thorac Ann 2006;14:51-56
© 2006 Asia Publishing EXchange Ltd
Cardiopulmonary Bypass Without Preoperative Exchange Transfusion in Sicklers
Madan M Maddali, MD,
Muthukkumar C Rajakumar, MCh,
Jutta Fahr, AFA,
Maher J Albahrani, FCCP,
Mohamed A Amna, MBChB
Department of Anesthesia, Department of Cardiothoracic Surgery, Royal Hospital, Muscat, Sultanate of Oman
For reprint information contact: Madan M Maddali, MD, Tel: 968 697 133, Fax: 968 697 133, Email: madan{at}omantel.net.om, Department of Anesthesia, Royal Hospital, PB No. 1331, PC. 111, Seeb, Muscat, Sultanate of Oman.
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ABSTRACT
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The effect of hypothermic cardiopulmonary bypass techniques on the sickling process was evaluated in patients with sickle cell hemoglobin. It was presumed that intraoperative hemolysis, as identified by hemoglobinuria, reflected increased sickling. Data of 43 patients with sickle cell traits and 2 with sickle cell disease, who were operated on under cardiopulmonary bypass and cold cardioplegic arrest in a tertiary center from the beginning of 1995 to the end of 2004, were retrospectively analyzed. A mean nasal temperature of 30.8°C ± 2.1°C was achieved. Three patients with sickle cell trait developed intraoperative hemoglobinuria, albeit with normal surrogate values for hemolysis. However, they had significantly lower mean hemoglobin levels during cardiopulmonary bypass compared to those sickle cell patients who did not exhibit hemoglobinuria (hemoglobin, 6.0 ± 0.2 vs. 7.4 ± 0.9 g·dL–1, p < 0.01). Total drainage and blood transfusion requirements in patients with normal and sickle cell hemoglobin were similar. It was concluded that hypothermic cardiopulmonary bypass with cold cardioplegia is safe in sickle cell patients. Maintenance of adequate hemoglobin levels during cardiopulmonary bypass may be important to avoid triggering a sickling process.
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INTRODUCTION
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Sickle cell hemoglobinopathies are inherited disorders ranging from a usually benign sickle cell trait (SCT) to the potentially fatal sickle cell anemia. Sickle cell trait is a heterozygous (Hb AS) manifestation where the concentration of sickle cell hemoglobin (HbS) is less than 50%. Sickle cell disease (SCD) is a homozygous genotype (Hb SS) with a fractional concentration of HbS varying from 70–98%. In this part of the world, the prevalence of SCT is 6% and SCD is approximately 0.2%.1 Patients with sickle cell abnormalities undergoing surgery are generally at greater risk of perioperative complications such as precipitation of sickle cell crisis, microvascular occlusion, increased red cell membrane fragility, and hemolysis.2 In addition, cardiopulmonary bypass (CPB) is associated with several predisposing factors for sickling (low flow states, aortic crossclamping, topical hypothermia, use of cold crystalloid cardioplegia, and hemodilution). The primary objective of this study was a retrospective assessment of the incidence of sickling in patients with sickle cell hemoglobinopathies, which resulted in hemolysis and hemoglobinuria during on-pump cardiac surgery. Parameters such as total drainage and transfusion requirements were compared with those of patients with normal hemoglobin who underwent similar surgery. The incidence of vaso-occlusive sequelae (renal or hepatic failure, stroke, or myocardial infarction) following hypothermic CPB, as well as mortality, was documented
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PATIENTS AND METHODS
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After approval from the institutional ethics committee, we analyzed the perioperative course of all cardiac surgical patients with sickle cell hemoglobinopathies who had undergone on-pump cardiac surgery at the Royal Hospital, Muscat, in the last 10 years (January 1st 1995 to end December 2004). Of 45 patients (43 with SCT and 2 with SCD), 29 had CABG surgery, 8 had single-valve replacements, and 8 had intracardiac repairs. All procedures were performed under hypothermic CPB and cold cardioplegia.
Baseline data, demographic and clinical characteristics are shown in Table 1
. All patients had electrophoretic studies for abnormal hemoglobin prior to surgery. After midazolam premedication, the patients were preoxygenated for 3–5 min. Anesthesia was induced with fentanyl, midazolam, thiopentone, pancuronium, and maintained with fentanyl, isoflurane and propofol throughout the surgical procedure. Propofol and fentanyl infusion were continued postoperatively for sedation and analgesia. No antifibrinolytics were used. Monitoring techniques were standard: electrocardiogram (EKG) with ST-segment analysis, peripheral oxygen saturation, end-tidal CO2, nasal and skin temperature, invasive arterial and central venous pressures, and urine output. Pulmonary artery catheters were used in CABG patients with poor ejection fraction or undergoing redo operations. Cardiopulmonary bypass parameters for good tissue perfusion, such as arterial inflow line pressure, cardiac index, and temperature gradients, as well as arterial and venous blood gas status, were routinely monitored. Venous oxygen saturation was kept above 75% in all patients. In pediatric patients, mean flow rates > 50 mL·kg–1·min–1 and perfusion pressures 
60 mm Hg were maintained at all times. During CPB, all patients received vasodilators (nitroglycerine or phentolamine) to improve peripheral perfusion and reduce stasis. All residual pump blood was discarded.
The CPB data collected were: lowest Hb on CPB, CPB and crossclamp times, lowest temperatures reached, type of prime (crystalloid/blood) and cardioplegia (blood/crystalloid), type of pump (roller/centrifugal), type of perfusion (pulsatile/non-pulsatile), and urine output (Table 1
). Postoperatively, total drainage during the first 24 h and total units of blood transfused were documented and compared to non-sickle cell patients in each surgical group. In patients who had hemoglobinuria on CPB, as detected by microscopy, surrogate variables for hemolysis were measured on reaching the post-cardiac surgery unit. The CPB data were evaluated against those of patients without hemoglobinuria (Table 2). The preoperative biochemical data were compared with those postoperatively (Table 3).
In all CABG and valve replacement patients, anticoagulation was initiated with heparin, overlapping with oral warfarin on the 3rd day. Heparin was withdrawn on the 6th postoperative day. Patients with intracardiac repair did not receive any type of anticoagulation in the postoperative period. For early identification of myocardial infarction, a 12 lead EKG was recorded immediately on reaching the post-cardiac surgery unit, and every day thereafter until discharge from the post-cardiac surgery unit. Any evidence of stroke was noted, and the final outcome was analyzed.
Discrete data and the relationship of hemoglobinuria to CPB parameters were analyzed by the Pearson chi-squared test. The paired-samples t test was used for the pre- and postoperative biochemical data. A p value of 0.05 or less was taken as significant. All numeric values are expressed as mean ± standard deviation.
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RESULTS
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All patients survived the operative procedures and were successfully discharged from hospital. The routine CPB parameters indicating good tissue perfusion were normal in all cases (Table 1). Three patients with SCT who underwent CABG had hemoglobinuria intraoperatively. Hemoglobinuria cleared in less than 6 h postoperatively in all 3 patients. The surrogate variables for detection of hemolysis were all normal: total hemoglobin 10.2 ± 0.8 g·dL–1, S-bilirubin 20 ± 7.1 µmol·L–1, lactic dehydrogenase 490 ± 65 IU·L–1, S-haptoglobin 170 ± 28 mg·L–1, reticulocyte count 0.2 ± 2%, and immature reticulocyte fraction 0.12 ± 0.09. The only abnormality detected during CPB was a low mean Hb of 6.0 ± 0.2 g·dL–1 corresponding to an approximate hematocrit of 18%, whereas the CABG patients with sickle cell hemoglobin who did not show hemoglobinuria had higher Hb values (7.4 ± 0.9 g·dL–1, p < 0.01). Other CPB data were similar in the CABG group with and without hemoglobinuria (Table 2). Once the low hematocrit was detected, crossmatched whole blood was added to the prime immediately. Electrophoresis performed postoperatively showed HbS values comparable to the preoperative levels in these patients. The preoperative and postoperative biochemical parameters in each group were normal (Table 3).
The 24-h drainage in patients with sickle cell hemoglobin undergoing CABG surgery was 817 ± 327 vs. 790 ± 336 mL ( p > 0.05) in 29 CABG patients with normal hemoglobin. In the sickle cell patients belonging to the valve replacement group, the total drainage in 24 h was 1,062 ± 303 vs. 966 ± 341 mL ( p > 0.05) in 8 patients with normal hemoglobin who had similar surgery. In the intracardiac repair group with sickle cell hemoglobin, drainage in the first 24 h was 185 ± 81 vs. 192 ± 79 mL ( p > 0.05) in 8 patients with normal hemoglobin who had similar surgery. None of the patients were re-explored for excessive drainage. Patients with sickle cell hemoglobin who underwent CABG surgery received 3.3 ± 0.7 units of blood per patient, while 3.1 ± 0.5 units were transfused in the 29 patients with normal hemoglobin ( p > 0.05).
Blood requirements in the valve group with sickle cell hemoglobin was 2.7 ± 0.6 vs. 2.6 ± 0.9 units per patient in the 8 patients with normal hemoglobin ( p > 0.05). The pediatric patients with sickle cell hemoglobin undergoing intracardiac repair needed 506 ± 175 mL of blood, whereas the 8 patients with normal hemoglobin and similar type of surgery required 498 ± 48 mL (one unit of blood = 350 mL of whole blood). None of the other patients showed any evidence of significant myocardial injury, either clinically or on the EKG. No patient suffered a stroke.
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DISCUSSION
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The current recommendations for the management of patients with SCT are essentially the same as for those with normal hemoglobin. Transfusions are needed only when there is substantial blood loss. Preoperative partial exchange transfusion to a hematocrit of 30–36% with HbS < 30% is recommended for major surgical procedures by some authors.3 Guidelines for the management of patients with SCD are more consistent. It is generally accepted that patients with SCD undergoing major surgery require reduction of HbS to < 30% to avoid a potential sickling crisis.4 Some reports suggest the addition of pre- and intraoperative exchange transfusion to reduce the percentage of sickle cells and prevent sickling and its sequelae.2,5–7 Currently, the protocols are more liberal; the emphasis lies on rehydration, and preoperative transfusion in SCD is only recommended in pronounced pre-existing anemia. While deciding on preoperative blood transfusions, it is important to weigh the risk of vaso-occlusive complications against the risks of multiple recurrent transfusions. For patients with SCD, risks of perioperative vaso-occlusive complications generally outweigh the risks of transfusion. In SCT patients, the risks of transfusion-transmitted disease generally outweigh the risks of vaso-occlusive complications and, therefore, preoperative red cell exchange transfusion is generally not indicated.3
The preoperative hemoglobin level has been identified as a strong predictor of perioperative blood transfusion in patients undergoing cardiac surgery.8–9 Usually, patients with a preoperative hemoglobin < 12 g·dL–1 require blood during the perioperative period.10 We did not encounter any increased transfusion requirements compared to patients with normal hemoglobin. In our series, none of the SCT patients had a preoperative exchange transfusion. No preoperative transfusions were deemed necessary in the 2 SCD patients, as their HbS levels were 35 and 40 g·dL–1 respectively. Although a transfusion trigger of hematocrit < 24% on CPB has been suggested, we transfused blood only when the hematocrit after cardioplegia administration was < 20%.11 In the postoperative period, a hematocrit < 24% was our trigger for transfusion. A blood prime was used in 9 of the 29 CABG patients, 3 of 8 patients undergoing valve replacements, and all cases of intracardiac repair. During CPB, 17 of the 45 patients (11 CABG, 4 valve replacement, and 2 intracardiac repair) required additional blood to maintain a hematocrit > 20%.
In this study, 3 of the 28 CABG patients with SCT required closer scrutiny and analysis, as they developed hemoglobinuria on CPB. Symptomatic identification of a sickle cell crisis leading to hemolysis in the perioperative period in cardiac surgical patients is difficult, as they are on artificial ventilation with sedation. Hence we presumed hemoglobinuria, as confirmed by microscopy, to represent an increased sickling process during CPB, and surrogate markers were measured to assess the degree of hemolysis. Total Hb and S-bilirubin are the parameters that change early during hemolysis. When hemolysis persists, lactic dehydrogenase and S-haptoglobin are the next parameters to rise, followed by an increase in reticulocyte count. These values were normal in the 3 patients, possibly indicating a short-lived hemolysis.
Sickling alone may not be the cause of hemolysis during bypass as other bypass-related processes might be involved. In this series, the CPB-related variables were comparable between patients who exhibited hemoglobinuria and those who did not. A centrifugal pump, which is supposed to cause minimal blood trauma, was used in all 3 patients who had intraoperative hemoglobinuria. There was no hypoxia or acidosis at any time. Therefore, we deduced that the intraoperative hemoglobinuria could be related to augmented sickling and hemolysis. The only abnormal parameter in patients who developed hemoglobinuria was a low hematocrit following cardioplegia administration, which might have triggered sickling and hemoglobinuria.
Sickle cell disorders are associated with a hypercoagulable state. Westerman and colleagues12 reported that d-dimer, thrombin-antithrombin, prothrombin fragment 1.2, and monocyte counts were proportionately higher with increasing severity of hemoglobinopathy (Hb AA, Hb AS, Hb SC, and Hb SS). Hence patients with SCD may be at increased risk of developing catastrophic vaso-occlusive complications. We did not encounter a predisposition towards vaso-occlusive events as there was no clinical evidence of myocardial infarction, stroke, or other organ failure. Possibly, early institution of anticoagulation in the postoperative period might have averted this problem. There is, however, a need to establish the safety of hypothermic CPB with cold cardioplegic arrest in patients with sickle cell hemoglobin. Previously, other authors have warned against the use of systemic hypothermia in these patients, as hypothermia increases the viscosity of blood and augments sickling.13–14 In patients with SCT, instances of systemic embolization and myocardial injury have been reported.5–15 Conversely, hypothermic CPB has been successfully used in patients with SCT and SCD during cardiac surgery.5,7,16 Topical hypothermia and application of an aortic crossclamp have also been applied successfully.5,7,17–18 Other techniques used include partial exchange transfusion prior to hypothermic CPB, limitation of hypothermia to 32°C, avoidance of intraoperative hypoxia, severe anemia, acidosis and postoperative reinfusion of mediastinal drainage.11
The mortality for SCT and SCD patients undergoing cardiac surgery varies from 10% to 13%.10,19 We had no mortality in our series and management of hemodynamics perioperatively played a major role in the successful outcome. High-flow bypass with aortic crossclamping, topical hypothermia, and cold crystalloid or blood cardioplegia were used in all our patients. This concurs with the observations of Pagani and colleagues.14 To avoid blood stasis, all our patients received vasodilators during CPB. Good cardiac output was maintained throughout. All, except one patient, were managed with regular inotropic and vasodilator drugs. The mean duration of postoperative mechanical ventilation in the CABG group was 22 ± 8.2 h, 18 ± 10.4 h in the valve replacement group, and 46 ± 12.1 h in the intracardiac repair group. The exception was a patient who underwent redo revascularization and developed intraoperative hemoglobinuria. He needed postoperative hemodynamic support with an intra-aortic balloon pump, and prolonged artificial ventilation. He was tracheostomized, successfully weaned off all inotropic supports by the 10th postoperative day, and de-cannulated on the 14th day. He was discharged home on the 20th postoperative day.
It was concluded that maintenance of appropriate hemoglobin concentrations may be more important in preventing the sickling process than the actual percentage of sickle cell hemoglobin. Patients with SCT may not need a preoperative transfusion unless surgical needs dictate otherwise. Hypothermic CPB, cold cardioplegia and topical hypothermia may be safely employed in patients with HbS. The effect of deep-hypothermic circulatory arrest on patients with hemoglobinopathies was not evaluated in this series. It may be possible to have a transfusion trigger below 20% during CPB, but the safety margin should be higher. A lower trigger, however, may reduce transfusion needs. Whether the patient has preoperative exchange transfusion or the concentration of HbS is diluted while going on bypass, there is still a small but nevertheless significant mass of HbS which may cause sickling in a hypoxic environment. This can be prevented by maintaining good perioperative PaO2 levels and shortened capillary transit times with the aid of vasodilators to ensure adequate capillary perfusion. The risk of vaso-occlusive episodes throughout the perioperative period should be kept in mind, and anticoagulants should be started early in the postoperative period.
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REFERENCES
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- Al-Riyami A, Ebrahim GJ. Genetic Blood Disorders Survey in the Sultanate of Oman. J Trop Pediatr 2003;49(Suppl 1):i1–20.
- Baxter MR, Bevan JC, Esseltine DW, Bernstein M. The management of two pediatric patients with sickle cell trait and sickle cell disease during cardiopulmonary bypass. J Cardiothorac Anesth 1989;3:477–80.[Medline]
- Kingsley CP, Chronister T, Cohen DJ, Parrish JM, Drew R, Bongiovanni MB. Case 2 – 1996. Anesthetic management of a patient with hemoglobin SS disease and mitral insufficiency for mitral valve repair. J Cardiothorac Vasc Anesth 1996;10:419–24.[Medline]
- Esseltine DW, Baxter MR, Bevan JC. Sickle cell states and the anaesthetist. Can J Anaesth 1988;35:385–403.[Medline]
- Fox MA, Abbott TR. Hypothermic cardiopulmonary bypass in a patient with sickle-cell trait. Anaesthesia 1984;39:1121–3.[Medline]
- Hudson I, Davidson IA, McGregor CG. Mitral valve replacement using cold cardioplegia in a patient with sickle cell trait. Thorax 1981;36:151–2.[Free Full Text]
- Balasundaram S, Duran CG, Al-Halees Z, Kassay M. Cardiopulmonary bypass in sickle cell anaemia. Report of five cases. J Cardiovasc Surg (Torino) 1991;32:271–4.[Medline]
- Cosgrove DM, Loop FD, Lytle BW, Gill CC, Golding LR, Taylor PC, et al. Determinants of blood utilization during myocardial revascularization. Ann Thorac Surg 1985;40:380–4.[Abstract]
- Karski JM, Mathieu M, Cheng D, Carroll J, Scott GJ. Etiology of preoperative anemia in patients undergoing scheduled cardiac surgery. Can J Anaesth 1999;46:979–82.[Medline]
- Djaiani GN, Cheng DC, Carroll JA, Yudin M, Karski JM. Fast-track cardiac anesthesia in patients with sickle cell abnormalities. Anesth Analg 1999;89:598–603.[Abstract/Free Full Text]
- Varvitsiotis PS, Jones JW, Nahas C, Beall AC. Myocardial revascularization in a sickle-cell trait patient. Cardiovasc Surg 1995;3:603–4.[Medline]
- Westerman MP, Green D, Gilman-Sachs A, Beaman K, Freels S, Boggio L, et al. Coagulation changes in individuals with sickle cell trait. Am J Hematol 2002;69:89–94.[Medline]
- deLeval MR, Taswell HF, Bowie EJ, Danielson GK. Open heart surgery in patients with inherited hemoglobinopathies, red cell dyscrasias, and coagulopathies. Arch Surg 1974;109:618–22.[Abstract/Free Full Text]
- Pagani FD, Polito RJ, Bolling SF. Mitral valve reconstruction in sickle cell disease. Ann Thorac Surg 1996;61:1841–3.[Abstract/Free Full Text]
- Leachman RD, Miller WT, Atias IM. Sickle cell trait complicated by sickle cell thrombi after open-heart surgery. Am Heart J 1967;74:268–70.[Medline]
- Frimpong-Boateng K, Amoah AG, Barwasser HM, Kallen C. Cardiopulmonary bypass in sickle cell anaemia without exchange transfusion. Eur J Cardiothorac Surg 1998;14:527–9.
- Marchant WA, Wright S. Aortic cross-clamping in sickle cell disease. Anaesthesia 2001;56:286–7.[Medline]
- Marchant WA, Wright S, Porter JB. Coronary artery bypass graft surgery in a patient with haemoglobin SC disease. Anaesthesia 2001;56:667–9.[Medline]
- Metras D, Coulibaly AO, Ouattara K, Longechaud A, Millet P, Chauvet J. Open-heart surgery in sickle-cell haemoglobinopathies: report of 15 cases. Thorax 1982;37:486–91.[Abstract/Free Full Text]
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J. Singh, S. Mehta, R. Sharma, S. S. Rana, S. K. Thingnam, and R. S. Dhaliwal
CARDIOPULMONARY BYPASS IN SICKLE CELL DISEASE
Asian Cardiovasc Thorac Ann,
October 1, 2006;
14(5):
445 - 446.
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ABSTRACT
INTRODUCTION
