A Practical Approach to Cardiac Anesthesia

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CHAPTER 9. The Postcardiopulmonary Bypass Period: A Systems Approach

Sibylle A. Ruesch and Jerrold H. Levy

Quick Links to Sections in this Chapter

–Cardiovascular system.

–Respiratory system

–Hematologic system

–Renal system

–Central nervous system

–Metabolic considerations

–Postbypass temperature regulation

The postcardiopulmonary bypass period represents a time in which the myocardium is recovering from the insult of surgery, cardiopulmonary bypass (CPB), and the potential inflammatory effects associated with extracorporeal circulation. During this period, major physiologic changes occur and they need to be understood in order to develop proper therapeutic approaches in patient management. The extent of these physiologic alterations and the time to recovery depend on numerous patient and surgical factors. This chapter identifies these physiologic changes and provides a systems approach to proper management of patients in the postbypass period.

  1. Cardiovascular system. The cardiovascular system is perhaps the system that undergoes the greatest physiologic stress during CPB and requires the most attention in the immediate postbypass period. Therefore, it is important to identify which factors may adversely affect cardiovascular outcome during this period.

    1. Factors contributing to adverse cardiovascular outcome in the postbypass period

      1. Patient factors

        1. Age. Patients older than 70 years suffer greater cardiac morbidity and mortality. Explanations for this observation include more extensive atherosclerosis, impairment of right ventricular (RV) or left ventricular (LV) function, and greater likelihood of coexistent medical illnesses, such as diabetes, chronic obstructive pulmonary disease, and peripheral vascular disease [1].

        2. Female gender. Women represent a high-risk group, particularly in those procedures involving myocardial revascularization. The reason for this is uncertain; however, it has been noted that women are older at the time of presentation for surgery, are less likely to be revascularized, have smaller coronary vessels, and more frequently are diabetic and hypertensive.

        3. Congestive heart failure. Preoperative ventricular dysfunction represents a significant risk factor and is associated with a higher mortality. Patients with the following conditions are likely to undergo a surgical procedure in congestive heart failure (CHF): (a) acute valvular dysfunction with hemodynamic deterioration, (b) recent myocardial infarction with ongoing ischemia despite optimal medical therapy, and (c) CHF secondary to significant impairment of LV/RV function.

        4. Emergency operation. Patients requiring emergent myocardial revascularization due to ongoing ischemia or hemodynamic deterioration after thrombolytic therapy, or unsuccessful angioplasty or stent placement also represent a high-risk group for multiple reasons. Some patients will be at greater risk for both prebypass and postbypass bleeding due to recent thrombolytic therapy, heparin administration, or recent use of platelet inhibitors including IIb/IIIa receptor antagonists and clopidogrel bisulfate (Plavix).

      2. Surgical factors

        1. During CPB

          1. Prolonged CPB. Although every revascularization is associated with some kind of transient myocardial impairment in the early postbypass period, the extent of it is mainly dependent on prebypass RV and LV function and degree of dyssynergy. With adequate myocardial preservation, myocardial damage is unlikely to occur in most individuals with aortic cross-clamping of less than 2 hours' duration [2]. Cross-clamping times exceeding this interval may result in impairment of myocardial performance. Also, as the duration of CPB increases, functional platelet abnormalities and the potential for bleeding and coagulopathy also increase.

          2. Inadequate repair

            1. Coronary artery. Myocardial revascularization may be inadequate for several reasons. The most common etiology is diffuse vascular disease distal to the site of the coronary anastomoses, which is most likely to occur in patients with smaller distal vessels, such as the elderly individuals, diabetics, and women. Other possible causes of impaired revascularization include technically difficult distal anastomoses as well as vein grafts or internal mammary arteries of poor quality, or, alternately, a diffusely atherosclerotic aorta where surgical technique was modified to avoid atheroembolic episodes.

            2. Valves. When a patient is hemodynamically unstable in the postbypass period after a valve replacement, first consideration must be given to a mechanical problem. Possibilities include (a) mechanical obstruction due to valve malfunction (stuck leaflet), (b) incorrect sewing of the valve (backward), (c) failure of a suture line resulting in a significant perivalvular leak, or (d) atrioventricular (AV) disruption after mitral valve replacement. Patients undergoing valve surgery also are placed at risk by the presence of intraventricular air, which may embolize to the coronary [preferably the right coronary artery (RCA) due to anatomic considerations] or carotid artery when the heart starts ejecting.

          3. Inadequate myocardial protection

            1. Inadequate myocardial cooling and cardioplegia administration. Optimal protection of the myocardium during CPB is essential for the prevention of prolonged postbypass cardiac dysfunction. The loss of cardiac contraction (asystole) has the greatest impact in reducing the cardiac metabolism, followed by hypothermia. Therefore, most surgeons use a combination of cold cardioplegia, moderate patient hypothermia, and topical application of ice slush to ensure adequate myocardial protection. Delivery of the cardioplegia is easier to the LV because several routes can be used (anterograde, retrograde, or combined). In contrast, the RV can only be correctly protected with anterograde cardioplegia because the retrograde delivery through the coronary sinuses is inhomogeneously distributed to the RV. Patients with significant RCA disease are therefore more at risk for postbypass RV dysfunction secondary to suboptimal myocardial protection and will rely on the topical cooling.

            2. Improper venting of the heart. Cardiac distention should be avoided because this leads to increased myocardial wall tension and increased O2 consumption. Several factors that may promote distention include increase in coronary collateral blood flow, aortic insufficiency, ventricular fibrillation (VF), and repeated administration of cardioplegia. Decompression is most commonly achieved with the use of an LV vent, which usually is inserted at the junction of the left atrium and right superior pulmonary vein or through the pulmonary artery (PA). Alternately, the left atrial appendage may be cut to allow spontaneous decompression. When venting is utilized, it is important to ensure that air is removed before ventricular ejection.

            3. Impaired myocardial perfusion. Coronary perfusion pressure is defined as the mean pressure in the aortic root during diastole minus LV intracavitary pressure. Although extensive debate exists as to what is the ideal coronary perfusion pressure, it is believed that a pressure between 50 and 70 mm Hg is adequate in most circumstances during CPB. Higher pressures may be required in cases of severe coronary stenosis, marked LV hypertrophy, and in instances where there is temporary ventricular distention. Myocardial flow also may be impaired at the time of reperfusion when emboli in the form of air or atheromatous debris may be present.

            4. Ventricular fibrillation has a deleterious effect on the heart, resulting in increased O2 consumption, elevated wall tension, and subsequent decrease in subendocardial flow. Appropriate management includes increasing coronary perfusion pressure, cooling the patient, and, if possible, immediately cross-clamping the aorta, with infusion of a cardioplegic agent to arrest the heart.

          4. Ventriculotomy. Ventriculotomy will lead to entrainment of air and debris into the heart and predispose to embolization of the coronary and cerebral circulations. It is a type of myocardial trauma that may contribute to impaired cardiac performance in the postbypass period.

          5. Reperfusion injury. Reperfusion injury describes a series of functional, structural, and metabolic alterations that result from reperfusion of myocardium after a period of temporary ischemia. The potential for this type of injury exists for all cardiac procedures where the aorta is clamped. The damage is characterized by (a) cytosolic accumulation of calcium; (b) marked cell swelling (myocardial edema), which decreases postischemic blood flow and ventricular compliance; and (c) generation of free radicals resulting from reintroduction of O2 during reperfusion. These oxygen-free radicals can cause membrane damage by lipid peroxidation. Various strategies are used to minimize injury, including reoxygenation with warm blood to start aerobic metabolism as well as other evolving strategies.

        2. Post-CPB

          1. Decannulation. When the patient is hemodynamically stable after separation from CPB, the venous cannula(s) is (are) removed. Blood loss and atrial dysrhythmias are the most common complications during repair of the atrial cannula site. After infusion of the appropriate volume of blood from the pump, the aortic cannula is clamped and removed. Although the timing and technique of removal vary among institutions, most centers remove the cannula before infusion of protamine. In addition, to minimize blood loss and prevent possible aortic disruption, the blood pressure frequently is lowered to reduce tension on the aortic wall. If, during aortic cannula removal, there is significant blood loss resulting in hemodynamic deterioration, a cannula may quickly be reinserted into the right atrium and the appropriate volume infused to achieve stability. However, some institutions will leave the aortic cannula in place during the initial infusion of protamine.

          2. Manipulation of the heart. The heart often is lifted after bypass, to allow examination of the distal anastomotic sites. The sequelae of this action include impaired venous return, atrial and ventricular dysrhythmias, and decreased ventricular ejection, all of which result in systemic hypotension. Manipulation such as this should be limited to brief periods in order to avoid ischemia and hemodynamic deterioration. Also, "overtreatment" of these hypotensive episodes with the administration of catecholamine boluses should be avoided, as it usually results in major hypertension when mechanical manipulation is stopped. Very high blood pressure at this stage can lead to graft disruption and increased bleeding.

          3. Myocardial ischemia

            1. Coronary artery spasm. Ischemia in the postbypass period may be secondary to spasm of the native coronary vessels or internal mammary artery. This typically manifests as ST-segment elevation, although dysrhythmias, severe hypotension, and cardiac arrest also may occur as sequelae. Mechanisms that have been proposed include intense coronary vasoconstriction from hypothermia, local trauma, respiratory alkalosis, excess sympathetic stimulation of the -receptors on the coronary vessels, release of vasoconstricting agents from platelets (thromboxane), and injury to native vascular endothelium with the loss of endogenous vascular relaxing factors (i.e., endothelium-derived relaxing factor and prostacyclin). Therapeutic modalities that have been used successfully to treat coronary spasm include intracoronary administration of drugs including nitroglycerin, papaverine, or systemic administration of nitroglycerin; calcium channel blockers (e.g., nicardipine); and other phosphodiesterase inhibitors (milrinone or inamrinone) [3].

            2. Mechanical obstruction. Compression of vein or internal mammary artery grafts can produce myocardial ischemia and should be considered. Ventilation with large tidal volumes can intermittently impair internal mammary artery graft flow and the distended lung can lead to disruption of the graft at the anastomotic site.

            3. Inadequate revascularization. See Section (2) above.

          4. Protamine administration. See Section III.A.4.

          5. Chest closure. During chest closure, hemodynamic deterioration may ensue. In general, patients with normal LV function and adequate intravascular volume tolerate closure without problems. Some patients experience mild hypotension and will respond promptly to volume administration. In individuals with poor ventricular function or patients currently receiving inotropic agents, additional volume or inotropic support may be required to maintain similar hemodynamics. If these interventions fail, the surgeon may be required to reopen the chest. Use of transesophageal echocardiography (TEE) can be especially useful to sort out the causes of hemodynamic instability, including myocardial ischemia with new wall-motion abnormalities or hypovolemia.

            Chest closure may cause cardiovascular deterioration for the following reasons. (a) In patients who have significant myocardial edema, closure will impair RV contractility and venous return. (b) Edematous, overdistended lungs can lead to a tamponade-like effect after closure in patient with severe chronic obstructive lung (pulmonary) disease (COPD). (c) A nonidentified source of bleeding before adaptation of the sternal borders can lead to cardiac tamponade with significant change in hemodynamics. (d) Finally, closure may result in a vein or internal mammary artery graft becoming kinked, with the development of ischemia in the area of the jeopardized myocardium. If these mechanical problems are eliminated and hemodynamics remain compromised, the chest may need to be left opened temporarily.

    2. Management of hemodynamics in the postbypass period. Proper management of patients in the postbypass period involves continuous assessment of five hemodynamic variables. These are preload, rate, rhythm, contractility, and afterload. Patients with new onset atrial fibrillation should be cardioverted and VF/ ventricular tachycardia (VT) should be shocked as well. For the patient with recurrent VT/VF despite defibrillation, intravenous amiodarone should be considered, based on the revised advanced cardiopulmonary life support (ACLS) guidelines, using a 150-mg load, 1 mg/min infusion, and additional 150-mg loads followed by defibrillation until an appropriate rhythm is established.

      1. Preload. Assessment of volume status is most commonly achieved by measuring the PA occlusion pressure (PAOP); however, the role of TEE in assessing ventricular volumes and preload is rapidly expanding in cardiac anesthesiology practice. What represents the ideal value will vary from one patient to another. Generally, however, a higher PAOP may be required postbypass to generate the same stroke volume because of a decrease in myocardial compliance. Other means of assessing preload include intermittent visualization of the heart until chest closure. Although administration of adequate volume is essential to optimize the patient's hemodynamics, it is of paramount importance to prevent ventricular distention.

      2. Rate. To achieve an adequate cardiac index, a faster heart rate may be required. Although the lower limit of heart rate has not been determined, a rate greater than 70 bpm is generally acceptable and easy to achieve with atrial pacing. Slow heart rates or atrial/ventricular dyssynchronization are one of the most easily correctable parameters affecting cardiac output. Pacing should always be kept in mind to improve hemodynamics if the patient's cardiac index falls.

      3. Rhythm. The ideal rhythm after bypass is sinus rhythm or atrial pacing in order to improve ventricular filling in the patient with a noncompliant LV after cardiac surgery, especially in the patient with preexisting ventricular dysfunction. Normally the "atrial kick" provides about 20% of ventricular filling, but this may be a significantly higher fraction after CPB, when ventricular dysfunction and reduced compliance are present. Other individuals will manifest variable degrees of AV block and require AV pacing after bypass. On occasion, rhythms such as supraventricular tachycardia or atrial fibrillation will occur and are best managed by cardioversion. Those patients with chronic atrial fibrillation usually are refractory to this therapy and require ventricular pacing. Even when pacing is not required postbypass, it is important to confirm that both the atrial and ventricular pacing wires are functional before chest closure and that pacing thresholds are not excessively high.

      4. Contractility. Contractility may be best assessed with TEE, but it is a complex parameter that often is assessed indirectly with different measurements. However, TEE is the only examination that can make a distinction between regional or global impairment of myocardial function and quantify LV function. Direct visualization of the heart can be used to assess contractility and volume status; however, it is predominantly the RV that is viewed through a median sternotomy. Although determination of cardiac index should be made initially after separation from bypass, multiple factors affect it. Cardiac index then should be measured at any time when there is a significant change in patient hemodynamics as well as after chest closure. Although a cardiac index of 2.2 L/min/m2 or greater is considered acceptable, the actual number is affected by rate, rhythm, and volume status. Before initiation of inotropic therapy, it is important to check heart rate and rhythm as well as the volume status of the patient. Optimization of these parameters may be all that is needed to augment cardiac index. If an inotrope is required, usually the choice of agent(s) will be based on preexisting ventricular dysfunction and down-regulation of -adrenergic receptors as well as anticipated problems with systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) [4].

      5. Afterload. Afterload is the force that opposes ventricular fiber shortening during systole. It is related directly to chamber dimension and inversely to wall thickness. In clinical practice, SVR is a parameter used to measure afterload. SVR; however, is only one component of ventricular afterload that is a derived hemodynamic parameter not routinely indexed to body surface area.

        Alterations in calculated SVR after bypass typically are manifested as changes in blood pressure and cardiac output. Increases in SVR may be related to an inadequate level of anesthesia, hypothermia, preexisting hypertension, intrinsic vascular disease, or use of drugs with vasoconstrictive properties. In patients with normal or elevated blood pressure and adequate cardiac index, reduction in vascular resistance can be achieved with a vasodilator (i.e., nitroglycerin, nicardipine, or nitroprusside) or an inhalational anesthetic agent. The intravenous calcium channel blockers (i.e., nicardipine) are arterial vasodilators, have no effects on the venous capacitance bed, and offer better choices when treating post-CPB hypertension in the patient with good ventricular function. If cardiac index is depressed, however, catecholamines alone or in combination with the cyclic adenosine monophosphate (cAMP)-specific (type III) phosphodiesterase inhibitors, such as milrinone, may be required.

        Etiologies of a low SVR postbypass include vasodilatory shock due to overwarming, use of angiotensin-converting enzyme (ACE) inhibitors, transfusion reactions, and anaphylactic/anaphylactoid reactions. Treatment will depend on the specific etiology. Management frequently includes use of an arteriolar vasoconstricting agent to maintain coronary perfusion pressure. Patients with an elevated cardiac index will benefit from either norepinephrine or phenylephrine. Patients with a depressed index will require an agent that has both - and -stimulating properties, such as norepinephrine. Norepinephrine is a safe and effective agent for treating hypotension in the postbypass period. For vasodilatory shock refractory to norepinephrine post-CPB, arginine vasopressin should be considered with a high cardiac index.

    3. Postbypass cardiovascular collapse. Although profound cardiovascular collapse after bypass is uncommon, it is likely that a technical problem (ischemia, valvular dysfunction) or severe metabolic derangement exists, and TEE should be considered to help make the correct diagnosis. If cardiovascular deterioration is unresponsive to maximal inotropic therapy and no immediate reversible cause can be identified (Fig. 9.1), then reinstitution of CPB will be necessary. When this decision is made, protamine, if being administered, must be stopped and the patient must receive a standard bolus dose of heparin. During the period that it takes to reestablish CPB, it is important to maintain coronary and cerebral perfusion with inotropes and vasopressors. In extreme circumstances it may be necessary for the surgical assistant to initiate open chest massage, while the surgeon places the arterial and venous cannulas.

      Fig. 9.1 Management scheme for cardiovascular dysfunction in the postbypass period. CPB, cardiopulmonary bypass; IABP, intraaortic balloon pump.

      When CPB is initiated, all inotropes and vasopressors should initially be stopped, because patients in this situation frequently become hypertensive. If blood pressure elevation is marked, the perfusionist can lower pump flow briefly while appropriate vasodilator therapy is given. Resumption of extracorporeal circulation will significantly lower myocardial oxygen requirements. Maintenance of a reasonable perfusion pressure is critical to allow adequate O2 delivery to potentially ischemic cells. This should be achieved with a pure agent such as phenylephrine. Despite lower O2 requirements and adequate supply, the ischemic cell may not be able to utilize O2 efficiently. This has resulted in the use of secondary cardioplegia.

      Additional recovery and reversal of damage can occur if the heart is rearrested with warm blood–enriched cardioplegia for a brief period. Consideration to separate from bypass should be made only after the surgeon is assured that technical difficulties did not account for impaired myocardial performance and that the heart is "adequately rested." In many cases, intraaortic balloon counterpulsation will be initiated to avoid the increased O2 demands associated with maximal inotrope therapy.

  2. Respiratory system

    1. Pulmonary edema

      1. Post-CPB pulmonary dysfunction. Pulmonary dysfunction after CPB is a common event; however, the extent and severity often vary. The alveolar-arterial (A-a) O2 gradient increases after bypass and becomes maximal at approximately 18 to 48 hours postoperatively. The ethology of this ventilation–perfusion mismatch is presumed to be an increase in pulmonary interstitial fluid and results in hypoxemia and hypercapnia. In its most severe state, a form of adult respiratory distress syndrome develops and is referred to as postperfusion lung syndrome [5]. Numerous etiologic factors have been suggested, including loss of surfactant, hypoxic damage to lung tissue, and pulmonary vasculitis caused by hemolyzed blood, protein denaturation, and multiple pulmonary emboli. Another mechanism of damage is lung accumulation of activated neutrophils containing lysosomal enzymes that produce pulmonary capillary damage and subsequent leakage of plasma. Transfusion reactions and transfusion-related acute lung injury also might play a role in pulmonary dysfunction. Postperfusion lung syndrome has virtually been eliminated today with the use of membrane oxygenators, which has greatly diminished blood trauma.

      2. LV dysfunction. Poor ventricular function in the postbypass period will result in elevated pulmonary venous pressures. This, combined with reduced colloid osmotic pressure secondary to hemodilution, will result in increased pulmonary interstitial fluid.

      3. Preexisting pulmonary edema. Individuals presenting for surgery with pulmonary edema represent a significant risk. These patients may be extremely difficult to oxygenate or ventilate after CPB. Techniques that may improve oxygenation include ultrafiltration and aggressive diuresis while on bypass.

      4. Anaphylactic reactions. Certain drugs, such as protamine, and administration of blood products or colloid volume expanders may, on rare occasions, cause an increase in pulmonary capillary permeability.

    2. Mechanical factors

      1. Pneumothorax occurs most commonly when the pleural cavity is entered during dissection of the internal mammary artery. Other etiologic factors include barotrauma from excess positive-pressure ventilation, particularly in patients with low lung or chest wall compliance, and entry into the pleural space as a complication of central venous access. A pneumothorax may manifest itself only after chest closure.

      2. Hemothorax. Accumulation of blood in the pleural cavity can occur during bypass as blood from the mediastinum frequently overfills the pericardial sling. It also may occur with dissection of the internal mammary artery before administration of heparin, which results in the collection of clot in the pleural space. The pleural space should be examined, and adequate removal of blood and clot is imperative before termination of CPB and before chest closure.

      3. Movement of the endotracheal tube. Draping the patient for cardiac procedures often will result in part of the head and endotracheal tube being obscured from direct vision. Even when the endotracheal tube is visualized, the surgeon frequently will push on this tube in an attempt to gain better surgical exposure, which may result in its displacement. Therefore, it is important intermittently to reconfirm proper positioning by checking all connections, observing bilateral chest movement, and visualizing one or both lung fields if the pleural cavities are exposed.

      4. Obstruction of the tracheobronchial tree

        1. Mucous plug. Dry inspissated secretions may accumulate in the tracheobronchial tree or endotracheal tube and partially or completely obstruct the airway. In most cases, this can be diagnosed and managed by suctioning the airway with a small catheter.

        2. Blood. Injury to the upper airway or trachea due to laryngoscopy, placement of an endotracheal tube, or an unrecognized preexistent airway lesion followed by heparinization may result in aspiration of blood. If significant, this can result in varying degrees of airway obstruction. More likely, however, the blood will be aspirated into the distal airways and alveoli, causing marked ventilation–perfusion mismatch. Blood also may appear in the airway due to perforation of the PA secondary to inappropriate management of the PA catheter. Frequent manipulation of the heart and continuous changes in intravascular volume may result in movement of the catheter into the wedge position. Subsequent balloon inflation could perforate the PA. Risk factors for inadvertent pulmonary artery catheter (PAC) displacement include advanced patient age, anticoagulation, hypothermia, and pulmonary hypertension.

    3. Protamine administration. See Section III.A.4.

    4. Intrapulmonary shunt

      1. Atelectasis. Perhaps the most common cause of decreased arterial oxygenation postbypass is atelectasis. Although diffuse, chest radiographs postoperatively frequently reveal a pattern of left lower lobe infiltration and atelectasis. The likely explanation is that application of ice causes temporary phrenic nerve injury with subsequent paralysis of the left leaf of the diaphragm. Attempts to prevent or attenuate atelectasis by ventilation of the nonperfused lungs during bypass have been unsuccessful.

      2. Inhibition of hypoxic pulmonary vasoconstriction. Hypoxic pulmonary vasoconstriction is the mechanism believed to be responsible for the increase in PVR in regions of atelectasis. This selective increase in resistance diverts blood away from hypoxic areas toward normoxic ventilated lung segments, thereby minimizing shunt. This protective mechanism can be attenuated or inhibited by the use of vasodilators (nitroprusside, nitroglycerin) and inotropes.

    5. Intracardiac shunt. When evaluating hypoxemia after CPB, the possibility of a right-to-left shunt must always be considered. Decreased RV contractility and compliance after CPB, in the presence of increased PVR associated with positive end-expiratory pressure (PEEP), frequently will elevate right atrial pressures above those on the left side. This equalization or reversal of pressure is the mechanism by which a patent foramen is opened. A helpful diagnostic tool in detecting a right-to-left shunt at the atrial level is TEE.

  3. Hematologic system

    1. Protamine

      1. Pharmacology. Protamine is a highly alkaline polycationic protein derived from salmon sperm that is predominantly arginine. Protamine binds the polyanionic glycosaminoglycan heparin and therefore neutralizes its effect. The clinical applications of protamine include neutralizing the effects of heparin and delaying the absorption of subcutaneously administered insulin.

      2. Dose. Various methods have been used to determine the appropriate dose of protamine needed to reverse the effects of heparin. Some of these are detailed here.

        In 1975, Bull et al. [6] recommended the quantitative neutralization of heparin. By using the heparin dose–response curve based on activated clotting time (ACT) just before separation from CPB, one could determine the amount of circulating heparin remaining. This relationship assumed that only heparin was responsible for ACT prolongation. Bull et al. recommended that 1.3 mg of protamine would adequately neutralize 100 units of circulating heparin in most individuals. However, this technique greatly overestimates the amount of protamine required at the end of CPB.

        The automated heparin protamine titration test represents a more precise method for determining the residual heparin concentration at the termination of bypass, by performing an in vitro neutralization of heparin based on different doses of protamine (Medtronic-HemoTec Heparin Monitoring System-HMS, Englewood, CO, U.S.A.). It automatically calculates the required dose of protamine. Using this technique, the total dose of protamine administered is less than that using a fixed protamine-heparin regimen.

        Most clinicians use fixed dosing of protamine for neutralizing heparin, which is based on a fixed protamine/heparin ratio determined by the total heparin administered during the initiation of CPB [7]. The ratio used is 0.5 to 1.0 mg of protamine for every 100 units of heparin given to the patient. Lower doses often are all that is required to reverse heparin, because heparin levels decrease with time.

      3. Route and rate. Protamine may be administered safely by either a central or a peripheral route. The most important factor in keeping hemodynamic changes at their lowest possible level is the rate of administration. Although this rate varies considerably among institutions, a suggested interval for the initial dose of protamine is as an infusion over 10 to 15 minutes, but no faster than 25 to 50 mg/min. Infusing protamine over 30 minutes may reduce the incidence of heparin rebound compared with administration over 5 minutes.

      4. Classification of protamine reactions. Multiple reactions to protamine have been described. The most life-threatening types of reactions are called anaphylaxis [8]. Anaphylactic reactions are mediated by immunoglobulin E antibodies, which bind to the surface of mast cells and basophils. Prior exposure to protamine or similar antigen is required to produce this sensitization. On reexposure, these cells will release histamine, prostaglandins, and chemotactic factors, thereby initiating an anaphylactic response characterized by vascular collapse. Anaphylactoid reactions are nonimmunologic and therefore do not require previous exposure to the antigen. Both immunoglobulin G (IgG) antibodies to protamine and heparin–protamine complexes can activate the complement system with the generation of fragments called anaphylatoxins. Complement-mediated reactions can range from mild changes to acute cardiovascular collapse, pulmonary vasoconstriction, and RV failure. The hemodynamic consequences of catastrophic pulmonary vasoconstriction include a several-fold increase in PA pressure followed by RV distention and hypokinesis. This obstruction to RV outflow results in severe systemic hypotension requiring inotropic support to restore circulatory stability. The presumed mechanism is the activation of complement, which results in the generation of thromboxane causing acute pulmonary vasoconstriction. This reaction may represent an anaphylactic reaction mediated by complement-fixing IgG antibodies. Therapy for these protamine reactions is listed in Table 9.1.

      5. Alternatives to protamine. Unfortunately, there are no current protamine alternatives available; however, several alternatives have been used for potential protamine allergic patients. Platelet factor 4 or heparinase has been used in clinical studies to reverse heparin in cardiac surgery [9]. Hexadimethrine (polybrene) is no longer available for clinical use.

        One alternative is removal of a major element in the coagulation cascade. Defibrinogenemia has been achieved with ancrod, an enzyme found in the Malayan pit viper. This form of anticoagulation for bypass has been used in a small group of individuals only. To assure its effectiveness as an anticoagulant, it is necessary to monitor fibrinogen levels.

        Protamine may be avoided by allowing the spontaneous termination of heparin's action. Although this has been used in individuals who are at risk for a protamine reaction, it represents a technique that results in increased blood product administration.

    2. Blood conservation

      1. Autologous transfusions

        1. Preoperative donation. Although preoperative autologous blood donations in patients undergoing cardiac surgery have been used, this is not practical for the majority of cardiac surgical patients, and it may not be cost effective.

        2. Prebypass phlebotomy/autologous normovolemic hemodilution. Intraoperative hemodilution by means of phlebotomy may reduce the requirement for homologous red blood cell transfusion [10]. Patients should have a hematocrit greater than 0.35 before blood is removed. The amount of removed blood varies from 1 to 3 units (500 to 1,500 mL) and depends on the baseline hematocrit as well as the age of the patient, the patient's body surface area, and the presence of any coexisting diseases [11]. Prebypass phlebotomy may be accomplished before heparinization and the blood placed in citrate phosphate dextrose (CPD) blood bags, or it may be done just before initiation of bypass, when blood is collected from the venous line of the CPB circuit.

        3. Intraoperative blood salvage. Blood that is lost before systemic heparinization or after protamine administration can be retrieved by a system that adds heparin or other anticoagulants. This salvaged blood is washed and filtered such that the remaining product is packed red blood cells. Several systems are commercially available for this purpose.

        4. Shed blood. Blood collected from both the mediastinum and pleural cavities in the postoperative period can be reinfused to the patient; however, this product collected from these sites does not clot due to defibrination, has an increased free hemoglobin content, and contains a spectrum of other hemostatic activation products that may not be ideal for reinfusion unless urgently needed or washed and spun.

      2. Acceptance of a lower hematocrit. What constitutes an acceptable postbypass hematocrit in patients undergoing cardiac surgery still remains controversial and varies among institutions. Patients who are healthy and demonstrate good ventricular function after bypass generally tolerate hematocrits in the range from 23% to 25%. Those individuals who have a reduced capacity to increase cardiac output, who continue to have limited coronary blood flow, or who have increased metabolic demands will require the increased O2-carrying capacity afforded by a higher hematocrit. Therefore, in patients with ventricular dysfunction and incomplete revascularization, as well as in older patients, packed red blood cells should be considered for the treatment of hypovolemia.

      3. Pharmacologic therapy

        1. Erythropoietin. Recombinant human erythropoietin stimulates the bone marrow to produce red blood cells. Current use of this product requires considerable amounts of time that often is not afforded in cardiac surgery and requires concomitant iron administration.

        2. Aprotinin. When administered before and during CPB, aprotinin significantly decreases postoperative bleeding and reduces the need for allogenic transfusions in cardiac surgical patients requiring CPB [12]. Aprotinin has been shown to be safe and effective in reducing transfusions in high-risk patients, and it is the only agent approved by the US Food and Drug Administration for this purpose. Multiple mechanisms of action are likely responsible, including antiinflammatory effects, inhibition of multiple proteases, and antifibrinolytic effects [13]. Aprotinin therapy should be instituted before incision and sternotomy.

        3. -Aminocaproic acid or tranexamic acid. Both -aminocaproic acid (EACA) and tranexamic acid are synthetic fibrinolytic inhibitors that act by occupying the lysine binding sites on plasminogen and plasmin. This, in turn, displaces these proteins from the lysine residues on fibrinogen and fibrin and interferes with the ability of plasmin to split fibrinogen. Although the routine use of fibrinolytic inhibitors in open heart surgery is controversial, it has been shown to result in modest reductions of bleeding after primary coronary bypass procedures.

        4. Desmopressin acetate. Desmopressin acetate (DDAVP) is believed to exert its effects by increasing the release of factor VIII(C) and von Willebrand factor. Von Willebrand factor multimers play a role in enhancing platelet adhesiveness. The prophylactic use of DDAVP (0.3 g/kg administered after bypass) in patients undergoing elective coronary artery bypass grafting was shown not to decrease blood loss or blood product administration. DDAVP may have a beneficial effect in certain subsets of patients including those with preexisting uremia.

  4. Renal system

    1. Effects of CPB on the kidneys. Many of the variables introduced with initiation of CPB have an effect on the renal system. Hemodilution, for example, reduces renal vascular resistance, resulting in increased flow to the outer renal cortex and subsequent enhanced urine flow. If systemic hypothermia is used as a form of myocardial protection, renal vascular resistance increases and renal blood flow, glomerular filtration rate, and free water clearance all decrease. Other variables that have the potential to impair renal function significantly in the postoperative period include microemboli and hemolysis of red blood cells.

    2. Postbypass renal dysfunction. Certain factors have been identified that place patients at risk for renal dysfunction in the postbypass period. These include elevated preoperative serum creatinine, combined valve and bypass procedures, and advanced age. Prolonged bypass times also may place patients at risk. Although a topic of some debate, the mode of perfusion (pulsatile vs. nonpulsatile) does not appear to influence perioperative renal function.

    3. Management. Pharmacologic therapy may have some benefit in patients with severe renal dysfunction or failure. A frequent observation is that urine flow is diminished during bypass compared with individuals who have normal renal function. This may result in significant hyperkalemia and accumulation of extracellular fluid. Administration of furosemide (initial dose 5 mg) or mannitol (0.5 to 1.0 mg/kg) has been shown to increase urine output in these patients. Fenoldopam in low dose (0.05 to 0.1 g/kg/min) will increased renal blood flow and may provide an important therapeutic option. Despite these interventions, some patients will require ultrafiltration during bypass or potentially dialysis in the early postoperative period.

  5. Central nervous system

    1. Anesthetic depth. The modern assessment of anesthetic depth with the bispectral index monitor adds important information for the proper management of the patient. In the postbypass period there are varying levels of surgical stimulation, with the highest being the placement of sternal wires and chest closure. If an increase in the depth of anesthesia is needed, the choice of agent(s) will depend primarily on the hemodynamic status of the patient.

      Small doses of opioids or benzodiazepines can be titrated incrementally in patients with stable hemodynamics. Additionally, judicious use of a volatile agent may be considered, particularly in patients who are hypertensive.

      Use of nitrous oxide should be avoided after bypass for several reasons. Nitrous oxide has the capability of enlarging air emboli that may have been generated during bypass. Many patients require high inspired concentrations of O2 during this period for reasons already mentioned. Finally, nitrous oxide can elevate PA pressures in those with preexisting pulmonary hypertension and can depress RV function.

      It must be remembered that all patients have some degree of postbypass ventricular dysfunction. Even small doses of narcotics have the potential to cause adverse hemodynamic consequences.

    2. Neuromuscular blockade. Patients frequently require additional neuromuscular relaxation in the postbypass period. The main objective is to prevent shivering, which in some circumstances can increase O2 consumption by 500%. To ensure adequate O2 delivery to tissues in this circumstance, an increase in cardiac output would be required that may not be possible without inotropic support. The muscle relaxant can be selected for its specific hemodynamic characteristics and duration of action.

  6. Metabolic considerations

    1. Electrolyte disturbances

      1. Hypokalemia is a relatively common electrolyte abnormality in the postbypass period. Although the etiologic factors of hypokalemia are numerous, only those unique to bypass will be mentioned. The kidney represents a major source of potassium loss. Both the preoperative and intraoperative use of diuretics, including mannitol administration on bypass, promotes significant potassium wasting. Glucose may be administered as a myocardial substrate during bypass. If significant hyperglycemia occurs, an osmotic diuresis with potassium loss will ensue. Hypokalemia also may result from the shift of potassium to the intracellular space. Such a shift may occur with alkalemia, from either hyperventilation or excess bicarbonate administration and with concomitant administration of insulin in a diabetic patient. In addition, use of inotropes capable of stimulating 2-receptors will promote the intracellular shift of potassium. Treatment will vary depending on the severity of hypokalemia. In most instances, intravenous administration up to 10 mEq/hour (in adults) will be effective. In life-threatening situations, potassium may be administered at a rate of 20 mEq/hour with continuous cardiac monitoring.

      2. Hyperkalemia occurs uncommonly after bypass. In most cases, hyperkalemia occurs when large doses of cardioplegic agents are administered, particularly in patients with impaired renal function. Hyperkalemia may persist in the postbypass period but generally resolves spontaneously without intervention. Depending on the cardiac rhythm, moderate hyperkalemia (potassium levels between 6.0 and 7.0 mEq/L) may require therapy with one of the treatment modalities listed in Table 9.2. With severe hyperkalemia (potassium levels greater than 7.0 mEq/L), all therapeutic interventions may be needed.

      3. Hypocalcemia can occur after bypass, although the incidence is unknown. Common etiologic factors include hemodilution from the pump prime, particularly in children; acute alkalemia; and calcium sequestration. Alkalemia that occurs with hyperventilation or rapid administration of parenteral bicarbonate results in enhanced binding of calcium to protein. Sequestration of calcium occurs with administration of a large volume of blood that contains the chelating agent citrate. Severe hypocalcemia results in myocardial depression and vasodilation.

        Calcium administration after CPB is indicated in the presence of severe hyperkalemia or in cases of hypotension associated with a low serum ionized calcium. Calcium may be administered as 10% calcium chloride (272 mg of elemental calcium) in a dose of 5 to 10 mg/kg.

        Routine administration of calcium after CPB is controversial because of its potential adverse effects. During the period of ischemia, there is a decrease in the production of high-energy phosphates, which results in the accumulation of cytosolic calcium. This increase in calcium during reperfusion reduces diastolic compliance and impairs relaxation. This fact must be considered when administering calcium in the postbypass period; however, the exact relationship between exogenously administered calcium and its intracellular accumulation has yet to be delineated.

      4. Hypomagnesemia commonly occurs in patients undergoing cardiac surgery. England and colleagues [14] suggested that large quantities of magnesium-free fluids with subsequent hemodilution most likely contribute to this observation. Other etiologic factors include loss of the cation in the extracorporeal circuit and redistribution of magnesium to other body stores. These authors conducted a randomized, controlled trial with patients in the treatment group receiving 2 g of magnesium chloride after termination of CPB. Magnesium-treated patients had a lower incidence of postoperative ventricular dysrhythmias and an increased cardiac index in the early postoperative period.

    2. Hyperglycemia. Certain groups of patients are at risk for developing hyperglycemia during cardiac surgery. Diabetics, particularly those who are insulin dependent, usually require an intraoperative insulin infusion to maintain glucose hemostasis. Glucose-containing solutions are used at some centers as the sole priming solution for the CPB circuit. Marked hyperglycemia may occur in patients on bypass and may persist into the postoperative period. Reported benefits from the use of such solutions include a reduction in perioperative fluid requirements and decreased fluid retention postoperatively. Use of inotropes, particularly epinephrine, after bypass may contribute to hyperglycemia by stimulating hepatic glycogenolysis and gluconeogenesis. The deleterious effects associated with hyperglycemia include an osmotic diuresis and the resulting electrolyte abnormalities, a potential to enhance both focal and global ischemic neurologic injury, and, if severe, coma. The use of glucose-containing solutions is no longer recommended.

  7. Postbypass temperature regulation

    1. Effects of hypothermia. All patients who undergo hypothermic CPB experience variable degrees of hypothermia in the postbypass period. This can have a profound effect on the cardiovascular system, particularly in individuals with borderline cardiac reserve. As the temperature decreases, arteriolar tone will increase, resulting in elevated SVR. The hemodynamic consequences of this include hypertension, a decrease in cardiac output, and increased myocardial O2 consumption. Total body O2 consumption may be increased because of the presence of shivering.

    2. Etiology of postbypass hypothermia. Hypothermic CPB results in a vasoconstricted state. During rewarming, many of these peripheral vascular beds (i.e., muscle and subcutaneous fat) do not adequately dilate and therefore act as a reserve of cold blood, which eventually will equilibrate with the central circulation. Opening and warming these vascular beds with pharmacologic vasodilation will diminish the "after-drop" in core temperature. The drop in temperature usually reaches its nadir 80 to 90 minutes after bypass.

    3. Prevention and treatment of hypothermia. The most effective way to attenuate postbypass hypothermia is to be assured that effective rewarming occurs during CPB. In many instances, the nasopharynx is the site of temperature measurement used to determine adequacy of rewarming. However, the nasopharynx reflects temperature of the central core, which receives a large percentage of the cardiac output and is not an indicator of the temperature in the peripheral tissues. A more appropriate site for monitoring the peripheral or shell temperature, therefore, is the rectum or the bladder. After-drop may be reduced by terminating CPB at a rectal temperature greater than 36°C.

      Other techniques that have been suggested to attenuate hypothermia include heating inspired gases, increasing ambient temperature, and using warm irrigation fluids in the chest cavity and warming blankets. The contribution of these techniques to preventing postbypass hypothermia is likely to be minor for the rewarming process but is of importance in maintaining the patient's temperature until he or she leaves the operating room.

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  1. Bailey JM, Levy JH, Hug CC. Cardiac surgical pharmacology. In: Edmunds H, ed. Adult cardiac surgery. New York: McGraw-Hill, 1997:225–254.
  2. Verrier ED. Cardiac surgery. J Am Coll Surg 1999;188:104–110.
  3. Huraux C, Makita T, Montes F, et al. A comparative evaluation of the effects of multiple vasodilators on human internal mammary artery. Anesthesiology 1998;88:1654–1659.
  4. Levy JH, Bailey JM, Deeb M. Intravenous milrinone in cardiac surgery.Ann Thorac Surg 2002;73:325–330.
  5. Byrick RJ, Kolton M, Hart JT, et al. Hypoxemia following cardiopulmonary bypass. Anesthesiology 1980;53:172–174.
  6. Bull BS, Huse WM, Brauer FS, et al. Heparin therapy during extracorporeal circulation. J Thorac Cardiovasc Surg 1975;69:685–689.
  7. Despotis GJ, Filos K, Gravlee G, et al. Anticoagulation monitoring during cardiac surgery: a survey of current practice and review of current and emerging techniques.Anesthesiology1999;91:1122–1151.
  8. Levy JH. Anaphylactic reactions in anesthesia and intensive care, 2nd ed. Boston: Butterworth-Heinemann, 1992.
  9. Mochizuki T, Olson PJ, Ramsay JG, et al. Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass. Anesth Analg 1998;87:781–785.
  10. Owings DV, Kruskall MS, Thurer RL, et al. Autologous blood donations prior to elective cardiac surgery. JAMA 1989;262:1963–1968.
  11. Levy JH. Blood conservation strategies. In: Cameron DE, Yang P, eds.Current therapy in thoracic and cardiovascular surgery.St. Louis: Mosby(in press).
  12. Levy JH, Pifarre R, Schaff H, et al. A multicenter, placebo-controlled, double-blind trial of aprotinin to reduce blood loss and the requirement of donor blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation 1995;92:2236–2244.
  13. Mojcik C, Levy JH. Systemic inflammatory response syndrome and anti-inflammatory strategies.Ann Thorac Surg2001;71:745–754.
  14. England MR, Gordon G, Salem M, et al. Magnesium administration and dysrhythmias after cardiac surgery. JAMA 1992;268:2395–2402.