Wang, Shigang; Lv, Shuyi; Guan, Yulong; Gao, Guodong; Li, Jingwen; Hei, Feilong; Long, Cun
Beijing Fuwai Hospital was founded in 1956 and also named Fuwai Hospital and Cardiovascular Institute, which is an affiliated cardiovascular-specific institution of Peking Union Medical College and Chinese Academy of Medical Sciences. With the rapid increase in economic growth and public transport development, an increasing number of patients from all over the country come to Fuwai Hospital for operations. Being the largest heart center in China, the number of operations in the cardiovascular surgery department reached 7,606 in 2008, despite the disastrous Wenchuan earthquake and the exceptional Beijing Olympic Games. After the development of cardiovascular surgery, cardiopulmonary bypass (CPB) technology gradually evolved into our own clinical routine as a production line of the “perfusion factory.” It has been demonstrated that our routine management of CPB can provide a safe, simple, and convenient CPB technique in supporting modern cardiac surgery that is suitable for practical clinical application in China.
Regardless of the increasing numbers of “off-pump” coronary artery bypass grafting (CABG) and interventional therapy, CPB technique is still an essential assisting method for open heart surgery. The potentially detrimental side effects of CPB are directly associated with perioperative morbidity and mortality in postoperative cardiac surgery patients. Therefore, clinical routine CPB management should be given increased attention to minimize the detrimental effects of CPB. This article summarizes our routine clinical CPB techniques in Fuwai Hospital in 2008 and is intended to share our perfusion techniques, clinical outcomes, and intended future technical improvements.
Methods and Materials
Tubing Circuits and Perfusion Equipments
Our perfusion tubing circuits are available in seven different types according to patient's body weight (Table 1). Other perfusion equipment and materials are described below:
1. Heart-lung machine: Jostra HL-20 (Maquet CP AG, Hirrlingen, Germany) and Stöckert SIII (Stöckert Instrumente, Münich, Germany).
2. Centrifugal pump: Bio-Medicus BioConsole 550 pump speed controller (Medtronic, Minneapolis, MN) and Jostra ROTAFLOW console (Maquet CP AG).
3. Heat-cooler unit: Jostra-20/30 (Maquet CP AG) and Stöckert S3 (Stöckert Instrumente).
4. Underbody forced-air warming blanket (Children) (WarmTouch 5800TM, Mallinckrodt Medical, St. Louis, MO) and homemade circulating water blanket (Adults).
5. Membrane oxygenator: Medtronic AFFINITY (Medtronic), Jostra Quadrox (Maquet CP AG), Xijian membrane oxygenator (adults, children, and infants) (Xijing Medical Equipment Co. Ltd., Xi'an, Shanxi, China), Terumo CAPIOX RX05 Baby-RX (Terumo, Tokyo, Japan), and Dideco 901/902 (Sorin, Mirandola, Italy).
6. Arterial filter: Ningbo arterial filter (adults, children, infants) (Flyer Medical Health care Co. Ltd., Ningbo, Zhejiang, China).
7. Perfect tubing pack with crystalloid or 4:1 blood cardioplegia delivery system (Perfect Biomedical Engineering Co. Ltd., Beijing, China).
8. Blood hemoconcentrator: Jostra BC 20/40 plus (Maquet CP AG).
9. BioTrend oxygen saturation and hematocrit monitor (Medtronic Cardiopulmonary, Anaheim, CA).
10. Homemade arterial line pressure monitor and low-level detector on the venous reservoir.
11. Sechrist oxygen/air mixer (Sechrist Industries, Anaheim, CA).
12. Hemochron Jr. Signature activated clotting time (ACT) analyzer (International Technidyne, Edison, NJ).
13. NOVA Biomedical CCX blood gas analyzer (Nova Biomedical, Waltham, MA).
14. Terumo CDI 500 monitoring system (Terumo Cardiovascular Systems, Tokyo, Japan).
15. Cell-saver system: Hemonetics cell saver 5 (Hemonetics Corp., Braintree, MA), Medtronic autoLog autotransfusion system (Medtronic, Minneapolis, MN), and Fresenius C.A.T.S. (Fresenius, Bad Homburg, Germany).
16. HemoCue plasma/low hemoglobin system (HemoCue, Inc., Lake Forest, CA).
17. Onkometer BMT 932 colloid osmometer (BMT Messtechnik GmbH, Berlin, Germany).
18. Thromboelastograph coagulation analyzer 3000 (Haemoscope Corp., Niles, IL).
Circuit Prime and CPB Management
A schematic drawing of the clinical circuit setup is shown in Figure 1. After assembling the CPB circuit, each circuit was flushed with CO2, deaired with lactated ringer's solution (adults) or plasmalyte-A solution (Baxter International Inc., Shanghai, China) (children), and all the solution in the venous reservoir was removed. For adults, 1,000 ml 6% hydroxyethyl starch 130/0.4 (Voluven; Fresenius Kabi, Bad Homburg, Germany) was added; for children, 1–2 units of leukocyte- depleted packed red blood cells, 100–200 ml fresh frozen plasma, and 20% albumin 50 ml were added. After that, excessive crystalloid solution was removed to keep venous reservoir blood level at 600 ml (adults) or 100 ml (children). Then, 4,000 (adults)/2,000 (children) units of heparin was added into CPB circuit and was circulated before the initiation of CPB.
After 400 unit/kg heparin was injected intravenously, the ACT was up to 400 seconds as the perfusion target. Cardiopulmonary bypass was set up routinely with ascending aorta and superior/inferior vena cava cannulations. Cardiopulmonary bypass was initiated using roller pump and hypothermic (nasopharyngeal temperature of approximately 30°C) nonpulsatile perfusion mode for all patients with conventional gravity venous drainage. The pump flow was maintained at 2.2–2.4 L/min/m2 (adults) or 2.4–3.0 L/min/m2 (children), and a mean systemic pressure of >60 mm Hg (adults) or 40 mm Hg (children) was obtained. Norepinephrine was given to maintain arterial pressure during CPB. After the nasopharyngeal temperature dropped below 34°C, the ascending aorta was cross-clamped and the heart was arrested using cardioplegic solutions through aortic root cannulation. Potassium, magnesium, and 5% sodium bicarbonate were added when necessary. Patients were rewarmed before termination of surgery. An antibiotic was administrated during rewarming. The aortic cross-clamp was released after adequate deairing, and the heart was reperfused to restore its spontaneous rhythm (if necessary, defibrillation of 20–30 W was applied). At the same time, 100 mg lidocaine was given (only in adults). Ten minutes after release of the aortic cross-clamp, 20 ml of 5% calcium gluconate was added. After rewarming to normal temperature (nasopharyngeal temperature 37°C, urinary bladder temperature >35°C), CPB was gradually weaned off, and heparin was reversed with protamine sulfate in a 1:1.5 ratio.
During the aortic cross clamping, we used cold modified St. Thomas crystalloid cardioplegia (children) and 4:1 cold blood cardioplegia (adults) for myocardial protection. The initial dose of crystalloid and blood cardioplegia was 20 ml/kg; the maintenance dose was 10 ml/kg every 30 minutes. Ice slush was used for topical hypothermia. Warm blood cardioplegia was sometimes used before releasing the aortic cross-clamping to wash out myocardial metabolic products and gaseous microemboli in the coronary circulatory system. Histidine- tryptophan-ketoglutarate (HTK) solution (Custodiol; Franz Koheler Chemie, Hahnlein-Ansbach, Germany) was used in some complex pediatric or adult patients. A single dose of cold HTK solution was 40–50 ml/kg, and infusion time was over 5–7 minutes, which can provide a safe period of 180 minutes of myocardial protection.
Deep Hypothermic Circulatory Arrest
For brain protection, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (SACP) were widely used as routine means for aortic arch reconstruction in our hospital. The proximal arterial line of our circuits has two branches through a Y-type connector. One branch connected to a 22–24 F Sarns arterial cannula (Sarns 3M Health Care, Ann Arbor, MI) which was inserted into the right axillary artery for CPB and SACP; the other branch was clamped. Once the nasopharyngeal temperature dropped to 18°C–20°C and the rectal (children) or the urinary bladder (adults) temperature to 20°C–22°C, SACP was conducted. Then, the brachiocephalic arteries were clamped. The perfusion flow rate was approximately 5–10 ml/kg/min. pH-stat blood gas management was used during DHCA + SACP. After the stent was implanted, the distal thoracic aortic anastomosis was performed; the lower body was then reperfused through another arterial line branch connected to the root branch of the four-branched graft. The side branches of the graft were attached to the brachiocephalic arteries separately, and proximal anastomosis was performed.
For pediatrics during SACP, the ascending aortic cannula was inserted forward into the innominate artery to maintain continuous perfusion of the brain. The left common carotid artery and left subclavian artery were ligated, respectively. The pump flow rate was reduced to 20–25 ml/kg/min, and the mixed venous oxygen saturation was >70%. Meanwhile, cerebral perfusion pressure (right radial artery pressure) was kept between 30 and 40 mm Hg, and the lower body maintained under circulatory arrest. After reconstruction, the aortic cannula was redirected into the ascending aorta, and the pump flow rate was recovered to full flow rate.
When the mixed venous oxygen saturation reached 85%, rewarming was started slowly. Five percent sodium bicarbonate 100–250 ml and 5–10 mg furosemide were added into the circuits (adults). Methylprednisolone was administered at initiation of CPB (15 mg/kg) and after rewarming (15 mg/kg). Twenty percent mannitol (0.5–1.0 g/kg) was given after urinary bladder temperature reached 30°C. Ultrafiltration was applied routinely to remove excess water and increase the level of hemoglobin during rewarming. Packed red blood cells were used when necessary.
Conventional ultrafiltration (with the inlet connected to the arterial filter purge line and outlet to the venous reservoir) and/or modified ultrafiltration after bypass (with the inlet connected to the arterial line and outlet to the venous line) were used in all infants and some adults, such as reoperative or great vessel surgery. Zero-balanced ultrafiltration was also used in some complex patients.
Cell Saver Blood Salvage and Transfusion
All off-pump coronary artery bypass grafting (CABG) and great vessel surgery required cell saver system to reduce intraoperative blood loss and homologous blood transfusion. The cell saver system may also be used in some complex pediatric congenital heart disease (CHD), reoperative surgery, and some adult open heart surgery in which there was rapid bleeding or high-volume blood loss. Packed red blood cells were added to the circuit to maintain patient hematocrit levels >20% (adults) or >24% (children) when necessary. At the end of CPB, the residual pump blood from the extracorporeal circuit was reinfused into patients or washed before reinfusion if there was CPB-induced hemolysis.
Extracorporeal Membrane Oxygenation
A few patients received extracorporeal membrane oxygenation (ECMO) support because of postoperative low cardiac output, severe hypoxemia, or failure to wean from CPB. We had two ECMO systems, Carmeda-ECMO system (Medtronic, Minneapolis, MN) and our modified Jostra-ECMO system. The former includes Carmeda AFFINITY NT or Minimax Plus hollow fiber oxygenator, Bio-Pump BP-50/BPX-80 Plus centrifugal blood pump with Bio-Medicus BioConsole 550 pump speed controller, cannulas, and tubings treated with Carmeda BioActive Surface; the latter consists of QUADROX D hollow fiber oxygenator with BIOLINE coating, ROTAFLOW Centrifugal Pump with ROTAFLOW console or Bio-Medicus BioConsole 550 pump speed controller with Rotaflow transverter, nonheparin-coated cannulas, and tubing. Almost all patients received the venoarterial ECMO support. Vascular access was achieved by the femoral artery and vein cannulations (adults) or the right atrial and ascending aorta cannulations (children). According to the hemodynamic and blood gas results, the ECMO flow was modified from 40 to 120 ml/kg/min. During ECMO support, intravenous inotropic doses and ventilator parameters were decreased gradually to reduce myocardial and pulmonary oxygen consumption and to promote heart or lung recovery. Activated clotting time was kept between 120 and 180 seconds unless the patient had excessive postoperative bleeding. Weaning strategy was dependent on echocardiograph, chest x-ray, and hemodynamic and blood gas results.
There are four heart centers in Fuwai Hospital, with a total of 16 operating rooms (ORs), including adult (8 ORs), pediatric (3 ORs), transplantation (2 ORs), and general (3 ORs) heart centers. In 2008, 7,606 cases of cardiac surgery of neonates, infants, children, and adults with various cardiovascular diseases were performed in Fuwai Hospital, including 4,470 males and 3,136 females. Figure 2 presents the number of surgical cases every month in 2008. Operative number had a correlation to seasons and festivals. The main disease composition is listed in Table 2. Congenital heart disease (48.33%) occupied the first position, whereas coronary artery disease (23.30%) and rheumatic heart disease (19.45%) were ranked in the second and third places, respectively. Isolated CABG was >50% of the off-pump CABG. In 2008, 38 cases of heart transplantation were performed, and total operative mortality was 1.2%. Average postoperative hospital stay was 9.5 days.
Age and body weight distributions of all patients are shown in Figures 3 and 4. Our primary patient population was aged between 1–5 years and 50–70 years. Figure 5 presents the total volumes (only during CPB) and cases using banked blood at different body weight intervals. Pediatric patients weighting 5–10 kg used more packed red blood cells than adult patients, who also consumed a great deal of banked blood.
More than 70% of patients experienced a CPB time <120 minutes, and the aortic cross-clamping time was <60 minutes in >50% of the cases (see Table 3). Nearly 10% of cases suffered from a CPB time of more than 180 minutes, and 94 cases underwent total/half aortic arch replacement combined with stented elephant trunk implantation. The mean CPB time was 201.0 ± 53.4 minutes, aortic cross-clamping time was 102.9 ± 29.9 minutes, lower body arrest time was 23.3 ± 12.8 minutes, and the minimum nasopharyngeal temperature was 18.2°C ± 1.1°C. Cold blood cardioplegia was our primary cardioplegic solution. The self-recovery rate in blood cardioplegia group was lower than that in the crystalloid cardioplegia group (see Table 4); 38 cases of heart transplantation used HTK as the preservation solution. Table 5 presents the total volumes of blood product (only for CPB), ultrafiltration, residual pump blood, and salvaged blood. The total volumes of ultrafiltration and residual pump blood were almost similar. A considerable amount of water was removed from patients, and a large volume of residual blood in CPB circuit was reinfused into patients postoperatively.
Thirty-five patients who underwent cardiac surgery and one patient who suffered from acute fulminant myocarditis required ECMO support due to postoperative cardiopulmonary dysfunction or serious heart failure. Age range was from 2 months to 71 years (mean 33.8 ± 24.1 years). Body weight range was from 3.2 to 85 kg (mean 46.6 ± 26.6 kg). ECMO support time was 20–235 hours (mean 116.8 ± 59.4 hours). A total of 27 patients (75.0%, mean support time 123.6 ± 54.1 hours) were weaned off ECMO successfully and were discharged without severe complications, whereas 9 patients (25.0%, mean support time 98.1 ± 65.6 hours) died. Primary complications were bleeding and renal failure.
Cardiopulmonary bypass is a primary circulatory support technique for cardiac surgery and remains one of the important factors associated with postoperative mortality and morbidity in open heart surgery. With improvements in equipment and techniques, CPB has become safer and more reliable. Nevertheless, perfusion-related incidents occasionally occur. Therefore, it was necessary for the perfusion team to establish a detailed CPB protocol to avoid such incidents and further improve the quality of perfusion. Clinical experience has proven that our current CPB protocol works well with present cardiac surgery with minimal clinical incidents. Using proven management methods, we have successfully trained many domestic perfusionists over the past decades.
To ensure perfusion safety, we currently use imported perfusion instruments of high quality and durability. In addition, the use of homemade disposable consumptive materials is very low: some circuit tubing and conventional cannulae and a small percentage of hollow fiber membrane oxygenators. To reduce the cost of CPB, we recommend further development of homemade CPB equipment and membrane oxygenators.
Almost all patients receive nonpulsatile perfusion during CPB; a few cases have used pulsatile flow for clinical research.1 The use of pulsatile flow has been restricted because not every heart-lung machine in our hospital can provide pulsatile mode, and more teaching is needed. No centrifugal pump was applied during CPB except when ECMO was used. Our standard clinical practice has been hypothermic CPB (nasopharyngeal temperature of approximately 30°C) with conventional gravity venous drainage; no assisted venous drainage device has been available in our center. During CPB, our primary safety measures have been the monitoring of arterial line pressure and the reservoir blood level detector. No bubble detector is used in our circuit. Continuous monitoring of mixed venous oxygen saturation and interval measurement of arterial blood gas are our most important means of ensuring adequate systemic oxygen delivery during CPB procedure. In-line blood gas monitors have not been adequate in all cases. Therefore, perfusion safety and quality may be expected under the current conditions, but further improvements are urgently needed.
In our center, 4:1 cold blood cardioplegia was used for all adults; cold modified St. Thomas crystalloid cardioplegia was applied for children; also, in some low-body-weight patients (<40 kg) undergoing a simple surgical operation, crystalloid cardioplegia may have been used. Blood cardioplegia was rarely used in pediatric patients. There is a simple cooling unit (a bucket of ice and water) in our cardioplegia circuit, which may result in inadequate cooling when a large amount of blood cardioplegia flows through the circuit. A separated heat exchanger will be needed for the administration of cardioplegia or for modified ultrafiltration. Because the first pediatric case was perfused with HTK during CPB in 2004, our cardiac surgeons now prefer using HTK solution in complex CHD pediatric patients. Our clinical experience and research demonstrated that HTK solution provided superior protection in immature myocardium2; a single flush of HTK solution is apparently adequate to protect the myocardium for an extended cold preservation time and to provide a surgical process without interruptions, resulting in a shortened duration of myocardial ischemia and a satisfying clinical outcome.3 Several things should be noted: the duration of HTK infusion is slightly longer and HTK infusion pressure is slightly lower than that of the St. Thomas crystalloid cardioplegia infusion; HTK solution should not be drawn into the CPB circuit; hyponatremia should be corrected with 10% NaCl before reperfusion of the myocardium.
Neurological monitoring during CPB was not available in our hospital in 2008. Neurological complications may occur after DHCA and low-flow CPB, especially in neonatal and senior patients. We have already realized the benefits of neurophysiologic monitoring during open heart surgery, but the cost of its devices and consumptive materials were the major restriction. Consequently, we relied only on our clinical experience and careful CPB management to minimize side effects in the absence of neurological monitoring, and so far, the clinical results have been satisfying.4,5 The neurophysiologic monitoring system should be adequately equipped in the future.
Conventional on-pump CABG is a safe and effective procedure, although it may evoke many side effects, such as postoperative inflammatory reaction, pulmonary dysfunction, intestinal ischemia, and neurological and cognitive dysfunctions. Off-pump CABG technique works on the beating heart without CPB, and many comparative studies have shown that it may reduce mortality and morbidity, decrease the postoperative blood loss and the need for transfusion accompanied by the use of cell saver, and shorten time periods on ventilation support and in intensive care. Senior patients in our hospital are willing to accept the off-pump CABG operation. More than half of the isolated CABG patients underwent this technique in Fuwai Hospital, and there has been an increasing trend of off-pump CABG in the past few years. Our off-pump CABG operation is usually performed as the first operation in the OR, provided there is a wet CPB circuit ready for emergency use; otherwise, it will be used for the next case.
Conventional and modified ultrafiltration effectively reduces total body water, raises the hematocrit value, decreases the need for transfusions, and eliminates inflammatory mediators. In our center, ultrafiltration was used in all infants who were <10 kg and some adults undergoing reoperative cardiac surgery or great vessel surgery. However, in the modified ultrafiltration system, we did not have a warming unit, which we would recommend as a further improvement for our center.
It is known that the use of a cell saver to salvage shed blood or residual circuit blood can reduce homologous transfusion, alleviate potential shortages in the blood supply, and cause no significant adverse impact on postoperative coagulation function. We recommend the use of autologous blood transfusion in all off-pump CABG surgery and some complex procedures. The processing of stored packed red blood cells with cell saver during infant CPB also can effectively increase hematocrit levels and remove cellular products and metabolites.6 The expense of the cell saver and its consumables limited its widespread clinical use, and there was no cost-effectiveness in using the device for those patients who salvaged <150 ml washed blood intraoperatively.
Because ECMO was introduced into our clinical service in December 2004, it has been used to support heart and lung function in the case of severe pre/postoperative cardiopulmonary dysfunction. The use of ECMO techniques greatly decreased our mortality rates in patients with serious circulatory or respiratory failure. Dr. Yuan7 and her coworkers8–10 reported our initial ECMO experiences and outcomes in Fuwai Hospital. With properly selected patients, optimal ECMO circuit, careful management, and growing clinical experience, ECMO therapy has become an accepted standard treatment for postoperative low cardiac output syndrome and severe hypoxemia, failure to wean from CPB, and as a bridge to heart transplantation in our center. However, we do not have the proper ECMO oxygenator for infants and are still using a centrifugal pump for neonates; high cost also restricted the application of ECMO.
Clinical CPB protocol in Beijing Fuwai Hospital is a safe, simple, and conventional CPB management system that is suitable for practical clinical application in China. Further optimization is still needed to improve perfusion quality and minimize the side effects of CPB.
The authors thank Liz Breach for her help in editing the manuscript.