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Pharmacologic Management of the Postoperative Cardiac Surgery Patient
Crit Care Nurs Clin N Am 19 (2007) 487–496
Pharmacologic Management of the Postoperative Cardiac Surgery Patient Elizabeth A. Katz, RN, MS, CCRN, ACNP Surgical Critical Care Services, Washington Hospital Center, 110 Irving Street, NW, 4B-42, Washington, DC 20010, USA
Early management of postoperative cardiac surgery patients focuses on optimizing cardiac output through aggressive resuscitation to prevent and treat potentially lethal complications while preserving adequate perfusion. Cardiac output is affected adversely by alterations in preload, contractility, heart rate and rhythm, and afterload. Each of these facets can have an impact, independently or simultaneously, on cardiac performance in the dynamic first postoperative hours. Myriad pharmacologic agents are used in the cardiac surgery intensive care setting to manage alterations in cardiac output. This article addresses many of the medications used in the immediate recovery period. These drugs are discussed in the context of their effect on the components of cardiac output and are those used at the author’s institution. Preload Decreased left ventricular preload is the leading cause of low cardiac output in immediate postoperative coronary artery bypass patients [1]. Preload, represented by ventricular end-diastolic volume and measured as end-diastolic pressure, represents the force that causes stretch in the myocardial fibers immediately before contraction. Preload can be influenced by heart rate and rhythm, contractility, ventricular performance, venous return, and vascular compliance. It is affected most adversely, however, during times of hypovolemia and vasodilatation by fluid shifts, hemorrhage, inflammatory responses, and rewarming.
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Hypovolemia and vasodilatation In the initial postoperative period, cardiac surgery patients are volume resuscitated aggressively with a combination of crystalloids and colloids to optimize preload. The majority of volume resuscitation occurs within 6 to 8 hours of arrival to an ICU and during this period, patients are likely to receive 1 to 3 liters of volume in 250 to 500 mL aliquots. Markers of adequate volume resuscitation include a stable blood pressure that provides a mean arterial pressure greater than or equal to 70 mm Hg, cardiac filling pressures (central venous pressure, pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure) of 12 to 22 mm Hg, or a cardiac index greater than 2.2 L/min/m2 or refractory to further fluid administration [1–3]. Norepinephrine Vasopressors are used to manage postoperative vasodilation and hypotension to maintain a mean arterial blood pressure greater than or equal to 70 mm Hg. Such medications generally are used when optimal volume resuscitation fails to maintain stable hemodynamics and cardiac output or when preload is impaired so severely that immediate and concurrent treatment with volume is necessary. Norepinephrine, with a1- and b1-adrenergic agonistic properties, is a potent vasopressor used to treat hypotension during the resuscitation of postoperative cardiac surgery patients. Dose-dependent arterial vasoconstriction results from stimulation of norepinephrine’s a1-adrenergic receptors, whereas inotropy and chronotropy occur with b1 stimulation. The a1 properties outweigh those of b1 because of the increase in afterload
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that occurs in direct response to increased systemic vascular resistance from b1 stimulation. Norepinephrine is dosed at 0.5 to 16 mg per minute in this patient population, although dose escalation is not uncommon, and generally is titrated to a mean arterial pressure goal. Although the onset of action is immediate, the offset (duration of time during which the drug loses effectiveness) occurs in approximately 2 to 3 minutes. Norepinephrine should be administered centrally to avoid local tissue necrosis and infiltration that can occur with peripheral delivery. The most significant side effect of norepinephrine in cardiac surgery patients is increased myocardial workload and oxygen consumption resulting from pronounced vasoconstriction. Other sites, such as the mesentery and kidneys, can become hypoperfused because of the vasoconstriction caused by norepinephrine, leading to detrimental organ damage [4]. Despite these effects, norepinephrine frequently is chosen over epinephrine as a vasopressor because of the tendency of epinephrine to cause an increase in cardiac work, systemic vascular resistance, and pulmonary artery occlusion pressure as a result of a1-adrenergic receptor activation at high doses [5]. Vasopressin Vasopressin, also known as antidiuretic hormone, is recognized as an effective treatment for hypotension resulting from cardiogenic and vasodilatory shock after cardiopulmonary bypass. Although the exact mechanism by which vasopressin causes vasoconstriction is unknown, it is postulated that it works by binding to V1 receptors on vascular smooth muscle cells, subsequently increasing peripheral resistance and inducing vasoconstriction of capillaries and arterioles [6]. Vasopressin use is more effective in patients who have endogenous vasopressin deficiency. Patients who have low ejection fractions and who have taken angiotensin-converting enzyme inhibitors preoperatively and who develop vasodilatory shock postoperatively have a substantial increase in blood pressure when treated with vasopressin [7]. Vasopressin is administered parenterally and continuously at a dose range of 0.01 to 0.10 units per minute. Used as an adjunct to other pressors, vasopressin therapy is initiated in response to escalating doses of other vasoactive drugs. This may reduce doses of other vasopressors and
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minimize their adverse effects. Side effects of vasopressin, although rare at these doses, include end-organ damage from hypoperfusion, hyponatremia, and increased afterload, all resulting from potent vasoconstriction [5].
Methylene blue Methylene blue, an inhibitor of nitric oxide, can be used to treat vasodilatory shock in patients who are refractory to vasopressor treatment. The release of nitric oxide in postcardiopulmonary bypass patients can cause severe vasodilation and vasoplegia, a syndrome defined by hypotension, normal or high cardiac indices, low filling pressures, low peripheral vascular resistance, and vasopressor dependence [8]. In 2004, Levin and colleagues [8] demonstrated that patients treated with methylene blue spend an average of 6 hours less time in a vasoplegic state and have a decreased risk for morbidity and mortality compared with patients treated with placebo. Methylene blue is administered by slow intravenous push, at a dose of 2 mg/kg, for the treatment of vasodilatory shock in the immediate postoperative resuscitation period. Hypertension, discoloration of urine, and transient, falsely low pulse oximetry readings (lasting less than 10 minutes) may be noted after the administration of the drug.
Hemorrhage Acute blood loss, from surgical or nonsurgical causes, can lead to decreased preload and, subsequently, decreased cardiac output. Coagulopathy is a common cause of nonsurgical bleeding and can result from insufficient reversal of heparin, platelet dysfunction (from cardiopulmonary bypass or preoperative medications), excessive platelet consumption, and fibronolysis. In addition, hypothermia, shivering, and hypertension can contribute to significant blood loss in an ICU. Surgical bleeding, typically resulting from inadequate hemostasis intraoperatively, requires a return to the operating room for invasive correction. First-line therapies used to treat postoperative hemorrhage include management of hypertension, rewarming, control of shivering, correction of coagulopathy (via pharmacologic agents or blood products), and treatment of anemia with blood transfusion.
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Protamine sulfate In patients who are coagulopathic as a result of insufficient reversal of heparin intraoperatively, protamine sulfate can be administered at a dose of 1 mg per 100 units of heparin to reverse anticoagulation up to a maximum dose of 50 mg. Although protamine sulfate contains inherent anticoagulant properties, it forms a salt when administered after heparin, halting the anticoagulation activity of both drugs. Given intravenously over 10 minutes, protamine sulfate has a neutralizing effect on heparin that occurs within 5 minutes of administration and lasts for 2 hours [9]. The administration of protamine sulfate is associated with severe systemic reactions, including hypotension, increased pulmonary artery pressures, bronchospasm, and noncardiogenic pulmonary edema, that contribute to intraoperative and postoperative morbidity and mortality. Protamine sulfate is made from a protein isolated from fish sperm, making patients who have a history of fish allergy, vasectomy, or other drug allergy at high risk for developing an anaphylactic reaction. Diabetics treated with NPH insulin also are more prone to developing protamine reactions as a result of the production of IgG protamine antibodies that can occur with initiation of such insulin therapy [10]. Aminocaproic acid Aminocaproic acid is an antifibrinolytic used to control postoperative bleeding that is secondary to excessive fibrinolysis. By preventing plasminogen from binding to fibrin and halting plasmin activation, aminocaproic acid can be effective in minimizing complications from postoperative hemorrhage. Aminocaproic acid is administered intravenously in the perioperative or postoperative setting. An initial dose (4 to 5 g given over 1 hour) is followed by a continuous infusion (1 g per hour for 8 hours or until bleeding is controlled). Adverse effects of aminocaproic acid, including thrombus formation, arrhythmias, thrombocytopenia, and rhabdomyolosis, are rare but potentially life threatening. Aprotinin Aprotinin is a protease inhibitor administered during cardiopulmonary bypass to reduce the inflammatory response, limit fibrinolysis, and decrease thrombin formation. The inhibition of inflammatory mediators is believed to decrease
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intraoperative bleeding and reduce the need for blood transfusion. Aprotinin is administered in a four-step regimen, with a test dose, loading dose, bypass pump priming dose, and maintenance dose infusion. Recent use of aprotinin has been limited by concerns about serious and potentially fatal side effects. In a study published in 2006, Mangano and colleagues [11] observed 4374 patients undergoing surgical revascularization after myocardial infarction. These patients prospectively were assigned to receive one of three antifibrinolytics/ serine protease inhibitors (aminocaproic acid, tranexamic acid, or aprotinin) and the safety of each drug was evaluated. In this investigation, aprotinin use was associated with a two- to threefold increased risk for renal failure requiring dialysis. Additionally, patients receiving aprotinin intraoperatively had a higher incidence of endorgan damage (myocardial infarction, heart failure, and encephalopathy), which may be attributed to microvascular thrombosis [11]. Recombinant activated factor VII Recombinant activated factor VII (rFVIIa) is a genetically engineered serine protease used to treat bleeding in patients who have coagulation factor deficiencies or antibodies to factor replacements. Although the exact mechanism by which rFVIIa causes hemostasis is unclear, it is postulated that thrombin generation is initiated from the formation of a complex with tissue factor at the site of injury or through the activation of factors IX and X on the platelet surface [12]. Off-label use of rFVIIa after cardiac surgery as a salvage therapy recently has become more prevalent. rFVIIa is used to treat coagulopathic bleeding either intraoperatively or postoperatively after the administration of blood products, including platelets, fresh frozen plasma, red blood cells, and cryoprecipitate [12]. Although rFVIIa is successful in controlling bleeding and limiting the amount of transfused products, its use has been limited by concerns of increased thromboembolic complications. More clinical trials investigating efficacy and safety of rFVIIa are needed before initiating routine use in the cardiac surgery population. Shivering Hypothermia, defined as a core temperature less than 35 C, is a common complication of cardiac surgery that results from loss of heat from the cardiopulmonary bypass machine, insufficient
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rewarming, administration of cold fluids, cardioplegia, transfusion of blood products, and exposure to room temperatures. In this patient population, hypothermia can result in vasoconstriction, hypertension, dysrhythmias, bleeding, and shivering [1]. In the cardiac surgery recovery setting, shivering may not be recognized immediately by a health care team because of anesthetic and paralytic agents used perioperatively. Therefore, close monitoring of hemodynamics, oxygen saturation, blood loss, end-tidal carbon dioxide levels, and clinical perfusion is imperative. Shivering in the critical care setting is managed by treating specific sequelae, such as increased oxygen consumption and carbon dioxide production. Furthermore, the addition of warm linens, infusion of warm fluids, and administration of opiates are successful treatment options [13]. Meperidine, the drug used most commonly in intensive care settings to manage postoperative shivering, controls shivering more effectively than equianalgesic doses of other opioids [14]. Meperidine is administered parenterally, at a dose of 12.5 to 50 mg every 15 to 20 minutes, until symptoms are controlled. The inherent antispasmodic and thermoregulatory properties of meperidine result in suppression of shivering that lasts for 1 to 2 hours and often prevents recurrence [14].
Contractility Contractility, a measure of the speed and intensity of myocardial contraction, is a vital component in the determination of cardiac output [15]. In the resuscitative postoperative period, contractility can be affected adversely by myocardial stunning and alterations in preload, afterload, heart rate, and rhythm. Pharmacologic agents used to aid contractility should be added once attempts have been made to optimize preload and afterload and achieve a stable rhythm. When resuscitation to achieve adequate preload, reduce afterload, and optimize rhythm fails to maintain adequate perfusion, and complications, such as tamponade, are ruled out, inotropes are used to increase contractility and subsequently increase cardiac output. Dobutamine Dobutamine, a synthetic sympathomimetic with marked b1- and b2-adrenergic agonistic
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activity but little a1-adrenergic activity, is a firstline inotropic agent used in the postoperative cardiac surgery setting. Dobutamine augments myocardial contractility primarily through potent b1-receptor stimulation. Cardiac output, however, also is augmented by b2-receptor–dependent vasodilation, which causes decreased systemic vascular resistance, increased coronary artery blood flow, and reduced afterload [4]. Because of the b2-induced vasodilatory effects of the drug, patients may require additional vasopressor support to maintain a mean arterial pressure greater than 70 mm Hg during dobutamine administration. The typical dose range for a dobutamine infusion is 2 to 20 mg/kg per minute, with an immediate onset of action and a 2- to 3-minute dissipation of effect. Side effects include hypotension, tachycardia (with a potential 25%–30% increase in heart rate as a result of b1-adrenergic agonistic activity), ventricular dysrhythmias, tachyphylaxis, and increased myocardial ischemia [2,4,16,17]. Tachyphylaxis can occur after several days of dobutamine infusion as a result of desensitization of b receptors. This phenomenon is more pronounced in patients who have chronic heart failure and those treated with b-blocking agents as a result of receptor downregulation and desensitization. Milrinone and amrinone Milrinone and amrinone are nonadrenergic phosphodiesterase inhibitors that increase myocardial contractility by increasing intracellular levels of cyclic adenosine monophosphate (cAMP) through the inhibition of cAMP degradation by phosphodiesterase. The inotropic properties of the drugs make them effective agents for the treatment of postoperative ventricular failure. Because both drugs cause vasodilation and subsequent hypotension because of b2 stimulation that occurs where cAMP is produced, phosphodiesterase inhibitors commonly require titration of additional vasopressors to maintain a goal mean arterial pressure [2]. Milrinone, unlike dobutamine, is effective in patients who have b-receptor downregulation. Milrinone is administered by continuous infusion at a dose range of 0.125 to 0.5 mg/kg per minute after a loading dose of 50 mg/kg. Eliminating the loading dose is acceptable to avoid the profound hypotension that typically accompanies the initial bolus. Despite a quick onset of action (5 minutes), the effects of milrinone last 2 to
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4 hours after dose titration or discontinuation [4,16]. Amrinone similarly causes increased cardiac output and decreased systemic vascular resistance. It has a 2- to 10-minute onset of action with drug effects lasting 1 to 2 hours. The dose range for amrinone is 10 to 30 mg/kg per minute after a bolus dose of 0.75 mg/kg. Amrinone’s use in clinical practice is limited because of the potential to cause profound thrombocytopenia [18]. Dopamine Dopamine possesses a- and b-adrenergic agonistic activity and is used as an inotrope to treat cardiogenic shock and hypotension effectively in postcardiac surgery patients. The effects of dopamine are dose dependent, and escalating doses can lead to increased myocardial oxygen demand and consumption, tachycardia, and decreased renal perfusion. At a dose of 1 to 2 mg/kg per minute, dopamine causes vasodilation in the renal, cerebral, coronary, and mesenteric vascular beds through stimulation of dopamine-1 receptors [19]. b1-adrenergic receptors are activated at doses of 5 to 10 mg/kg per minute and it is at this dose that the initial increase in cardiac output is seen as a result of increased stroke volume and myocardial contractility [20]. When dopamine is titrated to doses greater than 10 mg/kg per minute, a-receptors are activated, causing vasoconstriction and subsequent increased systemic vascular resistance. Dopamine is administered at a range of 1 to 20 mg/kg per minute (maximum dose 40 mg/kg/min) via continuous intravenous infusion into a central vein. Epinephrine Epinephrine has powerful b1-adrenergic receptor activity that causes inotropy and chronotropy and subsequently increases cardiac output at low doses. Thus, epinephrine is an effective choice in the treatment of postoperative cardiogenic shock. In addition to the b1 effects, epinephrine has a moderate but less potent effect on b2- and a1-adrenergic receptors, causing vasodilation and vasoconstriction, respectively. The competition between b2- and a1-receptor activation results in increased cardiac output, decreased systemic vascular resistance, and labile systemic pressures. The b2 and a1 effects are dose dependent, with b2-induced vasodilation occurring at low doses and a1 vasoconstriction and subsequent increased
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systemic vascular resistance prevailing at higher doses [5]. In this patient population, epinephrine is administered continuously via central venous access at a dose range of 1 to 10 mg per minute. Because of the potent b1-adrenergic receptor stimulation, patients treated with epinephrine infusions are prone to tachycardia and arrhythmias [4]. Other significant side effects of epinephrine administration include metabolic acidosis and severe hyperglycemia, both of which occur independently of dose and typically are seen in the first 6 to 8 hours after initiation of therapy. The development of metabolic acidosis from epinephrine administration is not well understood, although it is believed to be in response to b-receptor activation, ineffective metabolism, and subsequent accumulation of lactate that occurs with administration of the drug. The metabolic acidosis seen in these patients is not a result of hypoperfusion and typically portends a satisfactory prognosis as bicarbonate levels normalize with discontinuation of the drug [21,22]. Two types of lactic acidosis commonly are seen in critically ill patients [23]. Type A lactic acidosis is observed in patients suffering from shock, regional ischemia, severe respiratory compromise, or significant anemia. The resultant acidosis is a sequela of hypoperfusion or hypoxemia. Type B lactic acidosis occurs in the setting of adequate tissue perfusion and oxygenation. Genetic diseases, acquired diseases, toxins, and various medications, including epinephrine, are associated with this latter type of acidosis. Frequently, the metabolic acidosis seen in patients treated with epinephrine infusions is accompanied by adequate cardiac performance, evidenced by an adequate cardiac index and sufficient mixed venous oxygen saturation; thus, it is classified as a type B metabolic acidosis [23]. The hyperglycemia that occurs during epinephrine infusion likely is secondary to insulin resistance and enhanced gluconeogensis (from the stress response to epinephrine) and must be treated aggressively with high-dose intravenous insulin. After the discontinuation of epinephrine, blood sugar levels normalize and insulin requirements decrease dramatically [24]. Norepinephrine Norepinephrine, typically used to treat profound vasodilation and hypotension in cardiac
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surgery patients, is a weak inotrope that has a mild effect on cardiac output through activation of a1- and b1-adrenergic receptors (see previous discussion of norepinephrine). Isoproterenol Isoproterenol is different from the inotropes (discussed previously) in that it possesses affinity solely for b-adrenergic receptors. This results in intense inotropy and chronotropy, peripheral vasodilation, and increased myocardial oxygen consumption. Because of the latter, vigilance must be used with isoproterenol administration in patients who have untreated coronary artery disease and new or ongoing ischemia. Furthermore, isoproterenol should not be used in instances of profound hypotension because of the peripheral vasodilation that occurs through the activation of b2 receptors. In critical care postoperative settings, treatment with isoproterenol frequently is initiated in response to bradydysrhythmias, especially when temporary pacing is futile. Cardiac output, thus, is augmented by the subsequent increase in heart rate. Isoproterenol is useful further in right heart failure for reasons that remain unclear. The drug dilates the pulmonary vasculature, which has been hypothesized to reduced right ventricular afterload and increase function. Although there are no data to support this, isoproterenol seems to have a favorable effect on cardiac output in patients with right heart dysfunction. Isoproterenol is administered at a dose range of 1 to 4 mg per minute intravenously. The onset of action is immediate, with a 2- to 3-minute offset. Isoproterenol should be avoided in patients who have suspected ongoing ischemia because of the potential to increase oxygen demand. Tachycardia and lethal ventricular dysrhythmias are the most common adverse effects seen during acute administration [4]. Calcium chloride Intracellular levels of calcium positively mediate the inotropic state of the myocardium. Thus, intravenous calcium chloride often is administered intraoperatively to wean patients from cardiopulmonary bypass. Despite these inotropic effects, calcium increases vascular tone, which can lead to increased afterload, impaired diastolic function, and subsequent impairment of cardiac output when administered postoperatively. The effects
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of calcium administered intravenously are related directly to plasma calcium concentrations [25]. Calcium chloride can be used cautiously in the cardiac surgery population to further treat myocardial depression caused by hypocalcemia as a result of citrate toxicity from the transfusion of blood and blood products. Each unit of packed red blood cells contains the anticoagulant, citrate, which is metabolized hepatically every 5 minutes [26]. Citrate binds to ionized calcium, lowering serum calcium levels. Under normal circumstances, the body is able to compensate for the degree of hypocalcemia seen with blood transfusions. High-volume transfusions, hepatic dysfunction, rapid infusions, hypothermia, and shock, however, can portend citrate toxicity, decreasing ionized calcium levels further. Although a rare cause of hypocalcemia, citrate toxicity–induced hypocalcemia can lead to neuromuscular abnormalities, arrhythmias, and hypotension [26]. Calcium chloride has the potential to cause lethal dysrhythmias and should be administered slowly and vigilantly, especially in patients who have hypokalemia or digoxin toxicity. Calcium chloride is administered via central vein, in ampules of 100 or 200 mg, and effects are seen immediately [4].
Heart rate and rhythm Arrhythmias in postoperative CABG patients commonly are the result of electrolyte abnormalities, myocardial ischemia, decreased perfusion, hypoxemia, and medications [1]. Because alterations in heart rate and rhythm can be detrimental to cardiac output, temporary epicardial pacing wires routinely are placed intraoperatively. Ventricular arrhythmias in this patient population are treated according to the advanced cardiac life support guidelines [27]. Atrial and ventricular arrhythmias frequently are seen during recovery of postoperative CABG patients; however, atrial dysrhythmias are most common [28]. Approximately 25% to 40% of cardiac surgery patients develop atrial fibrillation postoperatively. Treatment of atrial arrhythmias in the acute recovery period revolves around maintenance or restoration of hemodynamic stability, perfusion, and cardiac performance [29]. Amiodarone Antiarrhythmic drugs are classified into four categories according to the Vaughan Williams
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antiarrhythmic classification scheme. Class I antiarrhythmics block sodium channels, class II agents block b-adrenergic responses, class III drugs increase the duration of the action potential, and class IV medications prevent the entry of calcium into the cell. Amiodarone is a unique antiarrhythmic in that it possesses the four properties of the Vaughan Williams scheme. This drug is used widely in postcardiopulmonary bypass patients because of its ability to treat rapidly and effectively a variety of atrial and ventricular rhythm disturbances. Amiodarone is effective in the conversion of atrial fibrillation to sinus rhythm and in the treatment of ventricular tachycardia and ventricular fibrillation. The pharmacokinetics of amiodarone are complex and not well understood. The drug has a large volume of distribution (60 L/kg), a profoundly long duration of action, and a half-life of 40 to 60 days. Because of these properties, amiodarone must be loaded intravenously or orally to facilitate achievement of a steady state. Intravenous loading, 150 mg over 10 minutes, can increase plasma concentrations of the drug rapidly. Secondary loading is done with an infusion of 1 mg per minute over a total of 6 hours followed by a maintenance infusion of 0.5 mg per minute. Acute intravenous administration of amiodarone can produce a significant drop in heart rate and blood pressure, although QRS duration and QT interval are preserved. In cardiac surgery patients, the resultant hypotension typically is transient. Cardiac surgery patients usually have temporary epicardial pacing wires, which allow for restoration of adequate heart rate in cases of hemodynamic instability from bradycardia. Chronic administration of amiodarone has the potential to cause further significant and potentially lethal side effects, including thyroid dysfunction, pulmonary fibrosis, vasodilation, hepatitis, skin discoloration, corneal microdeposits, and aggravation or potentiation of dysrhythmias [30]. Despite the potential for such adverse reactions, amiodarone remains one of the most effective antiarrhythmics in postcardiac surgery patients. Lidocaine Lidocaine is a class Ib drug used to treat ventricular arrhythmias by blocking the sodium channel in the cardiac action potential, thereby decreasing automaticity and depolarization of myocardial cells. Because of these properties,
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lidocaine is contraindicated in patients who have second- or third-degree heart block. Similarly, it is not approved for used in shock-refractory ventricular tachycardia and fibrillation. Lidocaine does not work on atrial tissues and, thus, is not useful in the treatment of atrial dysrhythmias [25]. Although lidocaine was the mainstay of treatment for ventricular dysrhythmias for decades, it has been replaced by amiodarone as a first-line antiarrhythmic [31]. Lidocaine is administered as a bolus of 1 to 1.5 mg/kg followed by an infusion of 50 to 70 mg/kg per minute. Lidocaine toxicity is associated with depressed central nervous system activity and may be recognized by seizures, altered levels of consciousness, and extreme lethargy, especially in patients who have impaired liver and kidney function. Electrolyte replacement Disturbances in heart rate and rhythm in the immediate postoperative period may be a result of potentially lethal causes (eg, vasospasm, ischemia, acidosis, or hypoxia); thus, extreme vigilance should be used in the evaluation of all dysrhythmias. Once malignant causes are eliminated, electrolyte replacement is a first-line therapy in the treatment of pathologic atrial and ventricular ectopy. In patients who have a normal serum creatinine, serum potassium levels should be kept between 4.0 and 5.0 mEq/L and magnesium levels greater than 2 mEq/L. Repletion of potassium and magnesium to such concentrations generally is sufficient to suppress ectopy and maintain adequate clinical perfusion. Other medications Several medications (discussed previously) also are used commonly in the acute postsurgical period because of their inherent abilities to influence heart rate and rhythm. Isoproterenol and dobutamine frequently are used to augment heart rate in patients who have sinus bradycardia or slow junctional rhythms. Epinephrine and vasopressin are part of the advanced cardiac life support algorithm for ventricular fibrillation and pulseless ventricular tachycardia [27]. Once the initial resuscitation phase is completed and patients are hemodynamically stable and only require minimal support, a variety of medications may be used to control arrhythmias. These include b-blockers, calcium channel blockers, and digoxin. The use of such medications is limited initially in
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the postoperative critical care setting by the prevalence of myocardial depression, hypotension, and bradydysrhythmias. The pharmacokinetics of these medications, however, make them effective chronic therapies for many of the arrhythmias that plague cardiac surgery patients. Although nitrates are the preferred medications of choice in managing postoperative hypertension, other medications can be used cautiously to control blood pressure. When acute, postoperative hypertension is associated with tachycardia, adequate cardiac output, and satisfactory left ventricular function, short-acting intravenous b-blockers, such as esmolol and labetalol, may be beneficial. The cardioselective properties, rapid onset of action, and ease of titration make esmolol a safe choice for management of hypertension in the immediate postoperative period. Similarly, labetalol, an aand b-blocker with vasodilatory properties, can be used to control blood pressure effectively in patients who have adequate contractility [1].
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congestion, and decreased myocardial oxygen consumption [2]. These effects are more pronounced when patients are volume resuscitated adequately. Nitroglycerin increases cardiac output by decreasing myocardial oxygen demand and increasing coronary artery perfusion. Unlike nitroprusside, nitroglycerin does not produce intracoronary steal and does not exacerbate ischemia [1]. Thus, it is a more favorable therapy for vasodilation and afterload reduction, especially in patients who may not have been completely reperfused surgically. The starting parenteral dose typically is 10 mg per minute and should be titrated in increments of 10 mg per minute to achieve a mean arterial blood pressure goal. The onset of action of nitroglycerin is immediate, with effects lasting 30 minutes [4]. Rapidly occurring hypotension is the most significant side effect of acute intravenous nitroglycerin administration. Other adverse reactions include tachy- and bradydysrhythmias, headache, and increased pulmonary ventilation-perfusion, resulting in hypoxemia [31].
Afterload Afterload is the force that blood ejected from the ventricles must overcome to cause myocardial contraction and pump blood into the pulmonic and systemic circulation effectively [4,15]. In the immediate postoperative period, cardiac surgery patients are prone to hypertension resulting from hypothermia, excessive catecholamine release, and subsequent vasoconstriction. The resultant increased afterload has several adverse sequelae, including metabolic acidosis from tissue ischemia, increased systemic vascular resistance, and decreased cardiac output [32,33]. Reducing afterload in post-CABG patients results in dilation of coronary arteries and reduction of myocardial wall tension and enddiastolic pressures, thereby improving oxygen delivery, decreasing oxygen consumption, and improving cardiac output [2]. Pharmacologic agents, rewarming mechanisms, and mechanical devices can aid in achieving decreased afterload during the immediate postoperative period. Nitroglycerin Vasodilators are the pharmacologic agents of choice to decrease afterload in the immediate postoperative period. Nitroglycerin is a venodilator that offers several benefits to cardiac surgery patients, including coronary artery dilation, prevention of vasospasm, decreased pulmonary
Nitroprusside Nitroprusside is used commonly in cardiac surgery intensive care units because of its potent ability to lower systemic vascular resistance and decrease afterload, thereby increasing cardiac output. In contrast to nitroglycerin, nitroprusside is a potent arterial dilator with fewer venodilator properties than nitroglycerin. Thus, hypertensive patients who have elevated left ventricular filling pressures and marginal cardiac indices benefit from the inherent arterial vasodilatory properties. Because nitroprusside is an effective vasodilator, vigilance must be used during administration to prevent a precipitous drop in mean arterial pressure. Nitroprusside is started, at a dose of 0.3 mg/kg per minute parenterally, and titrated every 10 minutes for blood pressure or cardiac index, to a maximum dose of 10 mg/kg per minute. The onset of action is immediate and effects dissipate rapidly after discontinuation [2,4]. In addition to clinically significant hypotension, side effects of nitroprusside in the cardiac surgery population include coronary steal, cyanide and thiocyanate toxicity, and lactic acidosis [1]. Hydralazine Hydralazine is an intravenously administered direct arterial dilator that causes smooth muscle
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relaxation by increasing intracellular levels of cyclic guanosine monophosphate. Because of the profound arterial dilatory effects and minimal venodilator effects of hydralazine, it is an effective afterload reducer. Hydralazine reduces systemic arterial pressures, inducing the baroreceptor reflex, which subsequently causes tachycardia, increased cardiac output, and renin release from heightened sympathetic outflow [34]. Administered at a dose of 5 to 20 mg, hydralazine’s effect on cardiac output can be seen within 15 to 30 minutes and lasts for 2 to 6 hours [4]. With acute administration, side effects include hypotension and reflex tachycardia. Significant adverse reactions associated with chronic administration include fever, neuropathies, vascular headaches, and a lupus-like syndrome that occurs with total daily doses greater than 200 mg [34].
Summary Maintaining adequate cardiac output in postoperative cardiac surgery patients is a complex and challenging feat for health care teams. Alterations in preload, afterload, contractility, heart rate, and rhythm can be devastating to these patients and lead to lethal consequences. An array of pharmacologic therapies is available in the critical care setting to help prevent and treat such complications and ensure satisfactory cardiac performance. References [1] Morris DC, Clements SD Jr, Bailey JM. Management of the patient after cardiac surgery. In: Fuster V, Alexander RW, O’Rourke RA, editors. Hurst’s the heart. 11th edition. New York: McGraw-Hill; 2004. p. 1509–16. [2] Timm C. Cardiogenic shock. In: Crawford MH, editor. Current diagnosis and treatment in cardiology. 2nd edition. New York: McGraw-Hill; 2003. p. 88–96. [3] St. Andre´ AC, DelRossi A. Hemodynamic management of patients in the first 24 hours after cardiac surgery. Crit Care Med 2005;33(9):2082–93. [4] Puyo CA, Lisbon A. Management of the postoperative cardiac surgical patients. In: Irwin RS, Rippe JM, editors. Intensive care medicine. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2003. p. 1637–51. [5] Rudis MI, Dasta JF. Vasopressors and inotropes in shock. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 435–51.
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[6] Albright TN, Zimmerman MA, Selzman CH. Vasopressin in the cardiac surgery intensive care unit. Am J Crit Care 2002;11:326–30. [7] Argenzino M, Chen JM, Choudhri AF, et al. Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg 1998;116:973–80. [8] Levin RL, Degrange MA, Bruno GF. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg 2004;77(2):496–9. [9] Haines ST, Racine E, Zeolla M. Venous thromboembolism. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 337–73. [10] Kimmel SE, Sekeres MA, Berlin JA, et al. Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass. J Am Coll Cardiol 1998;32(7): 1916–22. [11] Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354(4):353–65. [12] Enomoto TM, Thorborg P. Emerging off-label uses for recombinant activated factor VII: grading the evidence. Crit Care Clin 2005;2(3):611–32. [13] Holtzclaw BJ. Shivering in acutely ill vulnerable populations. AACN Clin Issues 2004;15(2): 267–79. [14] Kurz A, Ikeda T, Sessler DI, et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology 1997;86(5):1046–54. [15] Marino PL. Circulatory blood flow. In: Marino PL, editor. The ICU book. 2nd edition. Philadelphia: Lippincott Williams and Wilkins; 1998. p. 3–18. [16] Hollenberg SM, Parrillo JE. Cardiogenic shock. In: Parrillo JE, Dellinger RP, editors. Critical care medicine: principles of diagnosis and management in the adult. 2nd edition. St. Louis (MO): Mosby; 2002. p. 421–36. [17] Johnson-Davis A. Nesiritide therapy for acute heart failure. J Perianesth Nurs 2003;18(6):386–91. [18] Ansell J, Tiarks C, McCue C, et al. Amrinone induced thrombocytopenia. Arch Intern Med 1984; 144(5):949–52. [19] Dasta JF, Kirby MG. Pharmacology and therapeutic use of low-dose dopamine. Pharmacotherapy 1986;6(6):304–10. [20] Lollgen H, Drexler H. Use of inotropes in the critical care setting. Crit Care Med 1990;18(1 Pt 2):S56–60. [21] Raper RF, Cameron G, Walker D, et al. Type B lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25(1):46–51. [22] Totaro RJ, Raper RF. Epinephrine-induced lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25(10):1693–9.
496 [23] Mordes JP, Rossini AA. Lactic acidosis. In: Irwin RS, Rippe JM, editors. Intensive care medicine. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2003. p. 1186–94. [24] Caruso M, Orszulak TA, Miles JM. Lactic acidosis and insulin resistance associated with epinephrine administration in a patient with non-insulin-dependent diabetes mellitus. Arch Intern Med 1987;147(8):1422–4. [25] Bailey JM, Tanaka KA, Levy JH. Cardiac surgical pharmacology. In: Cohn LH, Edmunds LH Jr, editors. Cardiac surgery in the adult. New York: McGraw-Hill; 2003. p. 85–118. [26] Miller RD. Transfusion therapy. In: Miller RD, editor. Miller’s anesthesia. 6th edition. Philadelphia: Churchill Livingstone; 2005. p. 1799–812. [27] The American Heart Association. Advanced cardiac life support. Circulation 2005;112(22 Suppl 1): III-25–III-54. [28] Bradley D, Creswell LL, Hogue CW Jr, et al. Pharmacologic prophylaxis: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest 2005;128(Suppl 2):39S–47S.
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[29] Kailasam R, Palin CA, Hogue CW Jr. Atrial fibrillation after cardiac surgery: an evidence-based approach to prevention. Semin Cardiothorac Vasc Anesth 2005;9(1):77–85. [30] Bauman JL, Schoen MD. Arrhythmias. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 273–303. [31] The American Heart Association. 2005 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112(24 Suppl 1):IV-1–IV-203. [32] Kuttila K, Niinikoski J. Peripheral perfusion after cardiac surgery. Crit Care Med 1989;17(3): 217–20. [33] Downing SW, Edmunds LH Jr. Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg 1992;54(6):1236–43. [34] Carter BL, Saseen JJ. Hypertension. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 157–83.
Pharmacologic Management of the Postoperative Cardiac Surgery Patient Elizabeth A. Katz, RN, MS, CCRN, ACNP Surgical Critical Care Services, Washington Hospital Center, 110 Irving Street, NW, 4B-42, Washington, DC 20010, USA
Early management of postoperative cardiac surgery patients focuses on optimizing cardiac output through aggressive resuscitation to prevent and treat potentially lethal complications while preserving adequate perfusion. Cardiac output is affected adversely by alterations in preload, contractility, heart rate and rhythm, and afterload. Each of these facets can have an impact, independently or simultaneously, on cardiac performance in the dynamic first postoperative hours. Myriad pharmacologic agents are used in the cardiac surgery intensive care setting to manage alterations in cardiac output. This article addresses many of the medications used in the immediate recovery period. These drugs are discussed in the context of their effect on the components of cardiac output and are those used at the author’s institution. Preload Decreased left ventricular preload is the leading cause of low cardiac output in immediate postoperative coronary artery bypass patients [1]. Preload, represented by ventricular end-diastolic volume and measured as end-diastolic pressure, represents the force that causes stretch in the myocardial fibers immediately before contraction. Preload can be influenced by heart rate and rhythm, contractility, ventricular performance, venous return, and vascular compliance. It is affected most adversely, however, during times of hypovolemia and vasodilatation by fluid shifts, hemorrhage, inflammatory responses, and rewarming.
E-mail address: [email protected]
Hypovolemia and vasodilatation In the initial postoperative period, cardiac surgery patients are volume resuscitated aggressively with a combination of crystalloids and colloids to optimize preload. The majority of volume resuscitation occurs within 6 to 8 hours of arrival to an ICU and during this period, patients are likely to receive 1 to 3 liters of volume in 250 to 500 mL aliquots. Markers of adequate volume resuscitation include a stable blood pressure that provides a mean arterial pressure greater than or equal to 70 mm Hg, cardiac filling pressures (central venous pressure, pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure) of 12 to 22 mm Hg, or a cardiac index greater than 2.2 L/min/m2 or refractory to further fluid administration [1–3]. Norepinephrine Vasopressors are used to manage postoperative vasodilation and hypotension to maintain a mean arterial blood pressure greater than or equal to 70 mm Hg. Such medications generally are used when optimal volume resuscitation fails to maintain stable hemodynamics and cardiac output or when preload is impaired so severely that immediate and concurrent treatment with volume is necessary. Norepinephrine, with a1- and b1-adrenergic agonistic properties, is a potent vasopressor used to treat hypotension during the resuscitation of postoperative cardiac surgery patients. Dose-dependent arterial vasoconstriction results from stimulation of norepinephrine’s a1-adrenergic receptors, whereas inotropy and chronotropy occur with b1 stimulation. The a1 properties outweigh those of b1 because of the increase in afterload
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that occurs in direct response to increased systemic vascular resistance from b1 stimulation. Norepinephrine is dosed at 0.5 to 16 mg per minute in this patient population, although dose escalation is not uncommon, and generally is titrated to a mean arterial pressure goal. Although the onset of action is immediate, the offset (duration of time during which the drug loses effectiveness) occurs in approximately 2 to 3 minutes. Norepinephrine should be administered centrally to avoid local tissue necrosis and infiltration that can occur with peripheral delivery. The most significant side effect of norepinephrine in cardiac surgery patients is increased myocardial workload and oxygen consumption resulting from pronounced vasoconstriction. Other sites, such as the mesentery and kidneys, can become hypoperfused because of the vasoconstriction caused by norepinephrine, leading to detrimental organ damage [4]. Despite these effects, norepinephrine frequently is chosen over epinephrine as a vasopressor because of the tendency of epinephrine to cause an increase in cardiac work, systemic vascular resistance, and pulmonary artery occlusion pressure as a result of a1-adrenergic receptor activation at high doses [5]. Vasopressin Vasopressin, also known as antidiuretic hormone, is recognized as an effective treatment for hypotension resulting from cardiogenic and vasodilatory shock after cardiopulmonary bypass. Although the exact mechanism by which vasopressin causes vasoconstriction is unknown, it is postulated that it works by binding to V1 receptors on vascular smooth muscle cells, subsequently increasing peripheral resistance and inducing vasoconstriction of capillaries and arterioles [6]. Vasopressin use is more effective in patients who have endogenous vasopressin deficiency. Patients who have low ejection fractions and who have taken angiotensin-converting enzyme inhibitors preoperatively and who develop vasodilatory shock postoperatively have a substantial increase in blood pressure when treated with vasopressin [7]. Vasopressin is administered parenterally and continuously at a dose range of 0.01 to 0.10 units per minute. Used as an adjunct to other pressors, vasopressin therapy is initiated in response to escalating doses of other vasoactive drugs. This may reduce doses of other vasopressors and
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minimize their adverse effects. Side effects of vasopressin, although rare at these doses, include end-organ damage from hypoperfusion, hyponatremia, and increased afterload, all resulting from potent vasoconstriction [5].
Methylene blue Methylene blue, an inhibitor of nitric oxide, can be used to treat vasodilatory shock in patients who are refractory to vasopressor treatment. The release of nitric oxide in postcardiopulmonary bypass patients can cause severe vasodilation and vasoplegia, a syndrome defined by hypotension, normal or high cardiac indices, low filling pressures, low peripheral vascular resistance, and vasopressor dependence [8]. In 2004, Levin and colleagues [8] demonstrated that patients treated with methylene blue spend an average of 6 hours less time in a vasoplegic state and have a decreased risk for morbidity and mortality compared with patients treated with placebo. Methylene blue is administered by slow intravenous push, at a dose of 2 mg/kg, for the treatment of vasodilatory shock in the immediate postoperative resuscitation period. Hypertension, discoloration of urine, and transient, falsely low pulse oximetry readings (lasting less than 10 minutes) may be noted after the administration of the drug.
Hemorrhage Acute blood loss, from surgical or nonsurgical causes, can lead to decreased preload and, subsequently, decreased cardiac output. Coagulopathy is a common cause of nonsurgical bleeding and can result from insufficient reversal of heparin, platelet dysfunction (from cardiopulmonary bypass or preoperative medications), excessive platelet consumption, and fibronolysis. In addition, hypothermia, shivering, and hypertension can contribute to significant blood loss in an ICU. Surgical bleeding, typically resulting from inadequate hemostasis intraoperatively, requires a return to the operating room for invasive correction. First-line therapies used to treat postoperative hemorrhage include management of hypertension, rewarming, control of shivering, correction of coagulopathy (via pharmacologic agents or blood products), and treatment of anemia with blood transfusion.
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Protamine sulfate In patients who are coagulopathic as a result of insufficient reversal of heparin intraoperatively, protamine sulfate can be administered at a dose of 1 mg per 100 units of heparin to reverse anticoagulation up to a maximum dose of 50 mg. Although protamine sulfate contains inherent anticoagulant properties, it forms a salt when administered after heparin, halting the anticoagulation activity of both drugs. Given intravenously over 10 minutes, protamine sulfate has a neutralizing effect on heparin that occurs within 5 minutes of administration and lasts for 2 hours [9]. The administration of protamine sulfate is associated with severe systemic reactions, including hypotension, increased pulmonary artery pressures, bronchospasm, and noncardiogenic pulmonary edema, that contribute to intraoperative and postoperative morbidity and mortality. Protamine sulfate is made from a protein isolated from fish sperm, making patients who have a history of fish allergy, vasectomy, or other drug allergy at high risk for developing an anaphylactic reaction. Diabetics treated with NPH insulin also are more prone to developing protamine reactions as a result of the production of IgG protamine antibodies that can occur with initiation of such insulin therapy [10]. Aminocaproic acid Aminocaproic acid is an antifibrinolytic used to control postoperative bleeding that is secondary to excessive fibrinolysis. By preventing plasminogen from binding to fibrin and halting plasmin activation, aminocaproic acid can be effective in minimizing complications from postoperative hemorrhage. Aminocaproic acid is administered intravenously in the perioperative or postoperative setting. An initial dose (4 to 5 g given over 1 hour) is followed by a continuous infusion (1 g per hour for 8 hours or until bleeding is controlled). Adverse effects of aminocaproic acid, including thrombus formation, arrhythmias, thrombocytopenia, and rhabdomyolosis, are rare but potentially life threatening. Aprotinin Aprotinin is a protease inhibitor administered during cardiopulmonary bypass to reduce the inflammatory response, limit fibrinolysis, and decrease thrombin formation. The inhibition of inflammatory mediators is believed to decrease
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intraoperative bleeding and reduce the need for blood transfusion. Aprotinin is administered in a four-step regimen, with a test dose, loading dose, bypass pump priming dose, and maintenance dose infusion. Recent use of aprotinin has been limited by concerns about serious and potentially fatal side effects. In a study published in 2006, Mangano and colleagues [11] observed 4374 patients undergoing surgical revascularization after myocardial infarction. These patients prospectively were assigned to receive one of three antifibrinolytics/ serine protease inhibitors (aminocaproic acid, tranexamic acid, or aprotinin) and the safety of each drug was evaluated. In this investigation, aprotinin use was associated with a two- to threefold increased risk for renal failure requiring dialysis. Additionally, patients receiving aprotinin intraoperatively had a higher incidence of endorgan damage (myocardial infarction, heart failure, and encephalopathy), which may be attributed to microvascular thrombosis [11]. Recombinant activated factor VII Recombinant activated factor VII (rFVIIa) is a genetically engineered serine protease used to treat bleeding in patients who have coagulation factor deficiencies or antibodies to factor replacements. Although the exact mechanism by which rFVIIa causes hemostasis is unclear, it is postulated that thrombin generation is initiated from the formation of a complex with tissue factor at the site of injury or through the activation of factors IX and X on the platelet surface [12]. Off-label use of rFVIIa after cardiac surgery as a salvage therapy recently has become more prevalent. rFVIIa is used to treat coagulopathic bleeding either intraoperatively or postoperatively after the administration of blood products, including platelets, fresh frozen plasma, red blood cells, and cryoprecipitate [12]. Although rFVIIa is successful in controlling bleeding and limiting the amount of transfused products, its use has been limited by concerns of increased thromboembolic complications. More clinical trials investigating efficacy and safety of rFVIIa are needed before initiating routine use in the cardiac surgery population. Shivering Hypothermia, defined as a core temperature less than 35 C, is a common complication of cardiac surgery that results from loss of heat from the cardiopulmonary bypass machine, insufficient
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rewarming, administration of cold fluids, cardioplegia, transfusion of blood products, and exposure to room temperatures. In this patient population, hypothermia can result in vasoconstriction, hypertension, dysrhythmias, bleeding, and shivering [1]. In the cardiac surgery recovery setting, shivering may not be recognized immediately by a health care team because of anesthetic and paralytic agents used perioperatively. Therefore, close monitoring of hemodynamics, oxygen saturation, blood loss, end-tidal carbon dioxide levels, and clinical perfusion is imperative. Shivering in the critical care setting is managed by treating specific sequelae, such as increased oxygen consumption and carbon dioxide production. Furthermore, the addition of warm linens, infusion of warm fluids, and administration of opiates are successful treatment options [13]. Meperidine, the drug used most commonly in intensive care settings to manage postoperative shivering, controls shivering more effectively than equianalgesic doses of other opioids [14]. Meperidine is administered parenterally, at a dose of 12.5 to 50 mg every 15 to 20 minutes, until symptoms are controlled. The inherent antispasmodic and thermoregulatory properties of meperidine result in suppression of shivering that lasts for 1 to 2 hours and often prevents recurrence [14].
Contractility Contractility, a measure of the speed and intensity of myocardial contraction, is a vital component in the determination of cardiac output [15]. In the resuscitative postoperative period, contractility can be affected adversely by myocardial stunning and alterations in preload, afterload, heart rate, and rhythm. Pharmacologic agents used to aid contractility should be added once attempts have been made to optimize preload and afterload and achieve a stable rhythm. When resuscitation to achieve adequate preload, reduce afterload, and optimize rhythm fails to maintain adequate perfusion, and complications, such as tamponade, are ruled out, inotropes are used to increase contractility and subsequently increase cardiac output. Dobutamine Dobutamine, a synthetic sympathomimetic with marked b1- and b2-adrenergic agonistic
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activity but little a1-adrenergic activity, is a firstline inotropic agent used in the postoperative cardiac surgery setting. Dobutamine augments myocardial contractility primarily through potent b1-receptor stimulation. Cardiac output, however, also is augmented by b2-receptor–dependent vasodilation, which causes decreased systemic vascular resistance, increased coronary artery blood flow, and reduced afterload [4]. Because of the b2-induced vasodilatory effects of the drug, patients may require additional vasopressor support to maintain a mean arterial pressure greater than 70 mm Hg during dobutamine administration. The typical dose range for a dobutamine infusion is 2 to 20 mg/kg per minute, with an immediate onset of action and a 2- to 3-minute dissipation of effect. Side effects include hypotension, tachycardia (with a potential 25%–30% increase in heart rate as a result of b1-adrenergic agonistic activity), ventricular dysrhythmias, tachyphylaxis, and increased myocardial ischemia [2,4,16,17]. Tachyphylaxis can occur after several days of dobutamine infusion as a result of desensitization of b receptors. This phenomenon is more pronounced in patients who have chronic heart failure and those treated with b-blocking agents as a result of receptor downregulation and desensitization. Milrinone and amrinone Milrinone and amrinone are nonadrenergic phosphodiesterase inhibitors that increase myocardial contractility by increasing intracellular levels of cyclic adenosine monophosphate (cAMP) through the inhibition of cAMP degradation by phosphodiesterase. The inotropic properties of the drugs make them effective agents for the treatment of postoperative ventricular failure. Because both drugs cause vasodilation and subsequent hypotension because of b2 stimulation that occurs where cAMP is produced, phosphodiesterase inhibitors commonly require titration of additional vasopressors to maintain a goal mean arterial pressure [2]. Milrinone, unlike dobutamine, is effective in patients who have b-receptor downregulation. Milrinone is administered by continuous infusion at a dose range of 0.125 to 0.5 mg/kg per minute after a loading dose of 50 mg/kg. Eliminating the loading dose is acceptable to avoid the profound hypotension that typically accompanies the initial bolus. Despite a quick onset of action (5 minutes), the effects of milrinone last 2 to
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4 hours after dose titration or discontinuation [4,16]. Amrinone similarly causes increased cardiac output and decreased systemic vascular resistance. It has a 2- to 10-minute onset of action with drug effects lasting 1 to 2 hours. The dose range for amrinone is 10 to 30 mg/kg per minute after a bolus dose of 0.75 mg/kg. Amrinone’s use in clinical practice is limited because of the potential to cause profound thrombocytopenia [18]. Dopamine Dopamine possesses a- and b-adrenergic agonistic activity and is used as an inotrope to treat cardiogenic shock and hypotension effectively in postcardiac surgery patients. The effects of dopamine are dose dependent, and escalating doses can lead to increased myocardial oxygen demand and consumption, tachycardia, and decreased renal perfusion. At a dose of 1 to 2 mg/kg per minute, dopamine causes vasodilation in the renal, cerebral, coronary, and mesenteric vascular beds through stimulation of dopamine-1 receptors [19]. b1-adrenergic receptors are activated at doses of 5 to 10 mg/kg per minute and it is at this dose that the initial increase in cardiac output is seen as a result of increased stroke volume and myocardial contractility [20]. When dopamine is titrated to doses greater than 10 mg/kg per minute, a-receptors are activated, causing vasoconstriction and subsequent increased systemic vascular resistance. Dopamine is administered at a range of 1 to 20 mg/kg per minute (maximum dose 40 mg/kg/min) via continuous intravenous infusion into a central vein. Epinephrine Epinephrine has powerful b1-adrenergic receptor activity that causes inotropy and chronotropy and subsequently increases cardiac output at low doses. Thus, epinephrine is an effective choice in the treatment of postoperative cardiogenic shock. In addition to the b1 effects, epinephrine has a moderate but less potent effect on b2- and a1-adrenergic receptors, causing vasodilation and vasoconstriction, respectively. The competition between b2- and a1-receptor activation results in increased cardiac output, decreased systemic vascular resistance, and labile systemic pressures. The b2 and a1 effects are dose dependent, with b2-induced vasodilation occurring at low doses and a1 vasoconstriction and subsequent increased
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systemic vascular resistance prevailing at higher doses [5]. In this patient population, epinephrine is administered continuously via central venous access at a dose range of 1 to 10 mg per minute. Because of the potent b1-adrenergic receptor stimulation, patients treated with epinephrine infusions are prone to tachycardia and arrhythmias [4]. Other significant side effects of epinephrine administration include metabolic acidosis and severe hyperglycemia, both of which occur independently of dose and typically are seen in the first 6 to 8 hours after initiation of therapy. The development of metabolic acidosis from epinephrine administration is not well understood, although it is believed to be in response to b-receptor activation, ineffective metabolism, and subsequent accumulation of lactate that occurs with administration of the drug. The metabolic acidosis seen in these patients is not a result of hypoperfusion and typically portends a satisfactory prognosis as bicarbonate levels normalize with discontinuation of the drug [21,22]. Two types of lactic acidosis commonly are seen in critically ill patients [23]. Type A lactic acidosis is observed in patients suffering from shock, regional ischemia, severe respiratory compromise, or significant anemia. The resultant acidosis is a sequela of hypoperfusion or hypoxemia. Type B lactic acidosis occurs in the setting of adequate tissue perfusion and oxygenation. Genetic diseases, acquired diseases, toxins, and various medications, including epinephrine, are associated with this latter type of acidosis. Frequently, the metabolic acidosis seen in patients treated with epinephrine infusions is accompanied by adequate cardiac performance, evidenced by an adequate cardiac index and sufficient mixed venous oxygen saturation; thus, it is classified as a type B metabolic acidosis [23]. The hyperglycemia that occurs during epinephrine infusion likely is secondary to insulin resistance and enhanced gluconeogensis (from the stress response to epinephrine) and must be treated aggressively with high-dose intravenous insulin. After the discontinuation of epinephrine, blood sugar levels normalize and insulin requirements decrease dramatically [24]. Norepinephrine Norepinephrine, typically used to treat profound vasodilation and hypotension in cardiac
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surgery patients, is a weak inotrope that has a mild effect on cardiac output through activation of a1- and b1-adrenergic receptors (see previous discussion of norepinephrine). Isoproterenol Isoproterenol is different from the inotropes (discussed previously) in that it possesses affinity solely for b-adrenergic receptors. This results in intense inotropy and chronotropy, peripheral vasodilation, and increased myocardial oxygen consumption. Because of the latter, vigilance must be used with isoproterenol administration in patients who have untreated coronary artery disease and new or ongoing ischemia. Furthermore, isoproterenol should not be used in instances of profound hypotension because of the peripheral vasodilation that occurs through the activation of b2 receptors. In critical care postoperative settings, treatment with isoproterenol frequently is initiated in response to bradydysrhythmias, especially when temporary pacing is futile. Cardiac output, thus, is augmented by the subsequent increase in heart rate. Isoproterenol is useful further in right heart failure for reasons that remain unclear. The drug dilates the pulmonary vasculature, which has been hypothesized to reduced right ventricular afterload and increase function. Although there are no data to support this, isoproterenol seems to have a favorable effect on cardiac output in patients with right heart dysfunction. Isoproterenol is administered at a dose range of 1 to 4 mg per minute intravenously. The onset of action is immediate, with a 2- to 3-minute offset. Isoproterenol should be avoided in patients who have suspected ongoing ischemia because of the potential to increase oxygen demand. Tachycardia and lethal ventricular dysrhythmias are the most common adverse effects seen during acute administration [4]. Calcium chloride Intracellular levels of calcium positively mediate the inotropic state of the myocardium. Thus, intravenous calcium chloride often is administered intraoperatively to wean patients from cardiopulmonary bypass. Despite these inotropic effects, calcium increases vascular tone, which can lead to increased afterload, impaired diastolic function, and subsequent impairment of cardiac output when administered postoperatively. The effects
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of calcium administered intravenously are related directly to plasma calcium concentrations [25]. Calcium chloride can be used cautiously in the cardiac surgery population to further treat myocardial depression caused by hypocalcemia as a result of citrate toxicity from the transfusion of blood and blood products. Each unit of packed red blood cells contains the anticoagulant, citrate, which is metabolized hepatically every 5 minutes [26]. Citrate binds to ionized calcium, lowering serum calcium levels. Under normal circumstances, the body is able to compensate for the degree of hypocalcemia seen with blood transfusions. High-volume transfusions, hepatic dysfunction, rapid infusions, hypothermia, and shock, however, can portend citrate toxicity, decreasing ionized calcium levels further. Although a rare cause of hypocalcemia, citrate toxicity–induced hypocalcemia can lead to neuromuscular abnormalities, arrhythmias, and hypotension [26]. Calcium chloride has the potential to cause lethal dysrhythmias and should be administered slowly and vigilantly, especially in patients who have hypokalemia or digoxin toxicity. Calcium chloride is administered via central vein, in ampules of 100 or 200 mg, and effects are seen immediately [4].
Heart rate and rhythm Arrhythmias in postoperative CABG patients commonly are the result of electrolyte abnormalities, myocardial ischemia, decreased perfusion, hypoxemia, and medications [1]. Because alterations in heart rate and rhythm can be detrimental to cardiac output, temporary epicardial pacing wires routinely are placed intraoperatively. Ventricular arrhythmias in this patient population are treated according to the advanced cardiac life support guidelines [27]. Atrial and ventricular arrhythmias frequently are seen during recovery of postoperative CABG patients; however, atrial dysrhythmias are most common [28]. Approximately 25% to 40% of cardiac surgery patients develop atrial fibrillation postoperatively. Treatment of atrial arrhythmias in the acute recovery period revolves around maintenance or restoration of hemodynamic stability, perfusion, and cardiac performance [29]. Amiodarone Antiarrhythmic drugs are classified into four categories according to the Vaughan Williams
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antiarrhythmic classification scheme. Class I antiarrhythmics block sodium channels, class II agents block b-adrenergic responses, class III drugs increase the duration of the action potential, and class IV medications prevent the entry of calcium into the cell. Amiodarone is a unique antiarrhythmic in that it possesses the four properties of the Vaughan Williams scheme. This drug is used widely in postcardiopulmonary bypass patients because of its ability to treat rapidly and effectively a variety of atrial and ventricular rhythm disturbances. Amiodarone is effective in the conversion of atrial fibrillation to sinus rhythm and in the treatment of ventricular tachycardia and ventricular fibrillation. The pharmacokinetics of amiodarone are complex and not well understood. The drug has a large volume of distribution (60 L/kg), a profoundly long duration of action, and a half-life of 40 to 60 days. Because of these properties, amiodarone must be loaded intravenously or orally to facilitate achievement of a steady state. Intravenous loading, 150 mg over 10 minutes, can increase plasma concentrations of the drug rapidly. Secondary loading is done with an infusion of 1 mg per minute over a total of 6 hours followed by a maintenance infusion of 0.5 mg per minute. Acute intravenous administration of amiodarone can produce a significant drop in heart rate and blood pressure, although QRS duration and QT interval are preserved. In cardiac surgery patients, the resultant hypotension typically is transient. Cardiac surgery patients usually have temporary epicardial pacing wires, which allow for restoration of adequate heart rate in cases of hemodynamic instability from bradycardia. Chronic administration of amiodarone has the potential to cause further significant and potentially lethal side effects, including thyroid dysfunction, pulmonary fibrosis, vasodilation, hepatitis, skin discoloration, corneal microdeposits, and aggravation or potentiation of dysrhythmias [30]. Despite the potential for such adverse reactions, amiodarone remains one of the most effective antiarrhythmics in postcardiac surgery patients. Lidocaine Lidocaine is a class Ib drug used to treat ventricular arrhythmias by blocking the sodium channel in the cardiac action potential, thereby decreasing automaticity and depolarization of myocardial cells. Because of these properties,
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lidocaine is contraindicated in patients who have second- or third-degree heart block. Similarly, it is not approved for used in shock-refractory ventricular tachycardia and fibrillation. Lidocaine does not work on atrial tissues and, thus, is not useful in the treatment of atrial dysrhythmias [25]. Although lidocaine was the mainstay of treatment for ventricular dysrhythmias for decades, it has been replaced by amiodarone as a first-line antiarrhythmic [31]. Lidocaine is administered as a bolus of 1 to 1.5 mg/kg followed by an infusion of 50 to 70 mg/kg per minute. Lidocaine toxicity is associated with depressed central nervous system activity and may be recognized by seizures, altered levels of consciousness, and extreme lethargy, especially in patients who have impaired liver and kidney function. Electrolyte replacement Disturbances in heart rate and rhythm in the immediate postoperative period may be a result of potentially lethal causes (eg, vasospasm, ischemia, acidosis, or hypoxia); thus, extreme vigilance should be used in the evaluation of all dysrhythmias. Once malignant causes are eliminated, electrolyte replacement is a first-line therapy in the treatment of pathologic atrial and ventricular ectopy. In patients who have a normal serum creatinine, serum potassium levels should be kept between 4.0 and 5.0 mEq/L and magnesium levels greater than 2 mEq/L. Repletion of potassium and magnesium to such concentrations generally is sufficient to suppress ectopy and maintain adequate clinical perfusion. Other medications Several medications (discussed previously) also are used commonly in the acute postsurgical period because of their inherent abilities to influence heart rate and rhythm. Isoproterenol and dobutamine frequently are used to augment heart rate in patients who have sinus bradycardia or slow junctional rhythms. Epinephrine and vasopressin are part of the advanced cardiac life support algorithm for ventricular fibrillation and pulseless ventricular tachycardia [27]. Once the initial resuscitation phase is completed and patients are hemodynamically stable and only require minimal support, a variety of medications may be used to control arrhythmias. These include b-blockers, calcium channel blockers, and digoxin. The use of such medications is limited initially in
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the postoperative critical care setting by the prevalence of myocardial depression, hypotension, and bradydysrhythmias. The pharmacokinetics of these medications, however, make them effective chronic therapies for many of the arrhythmias that plague cardiac surgery patients. Although nitrates are the preferred medications of choice in managing postoperative hypertension, other medications can be used cautiously to control blood pressure. When acute, postoperative hypertension is associated with tachycardia, adequate cardiac output, and satisfactory left ventricular function, short-acting intravenous b-blockers, such as esmolol and labetalol, may be beneficial. The cardioselective properties, rapid onset of action, and ease of titration make esmolol a safe choice for management of hypertension in the immediate postoperative period. Similarly, labetalol, an aand b-blocker with vasodilatory properties, can be used to control blood pressure effectively in patients who have adequate contractility [1].
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congestion, and decreased myocardial oxygen consumption [2]. These effects are more pronounced when patients are volume resuscitated adequately. Nitroglycerin increases cardiac output by decreasing myocardial oxygen demand and increasing coronary artery perfusion. Unlike nitroprusside, nitroglycerin does not produce intracoronary steal and does not exacerbate ischemia [1]. Thus, it is a more favorable therapy for vasodilation and afterload reduction, especially in patients who may not have been completely reperfused surgically. The starting parenteral dose typically is 10 mg per minute and should be titrated in increments of 10 mg per minute to achieve a mean arterial blood pressure goal. The onset of action of nitroglycerin is immediate, with effects lasting 30 minutes [4]. Rapidly occurring hypotension is the most significant side effect of acute intravenous nitroglycerin administration. Other adverse reactions include tachy- and bradydysrhythmias, headache, and increased pulmonary ventilation-perfusion, resulting in hypoxemia [31].
Afterload Afterload is the force that blood ejected from the ventricles must overcome to cause myocardial contraction and pump blood into the pulmonic and systemic circulation effectively [4,15]. In the immediate postoperative period, cardiac surgery patients are prone to hypertension resulting from hypothermia, excessive catecholamine release, and subsequent vasoconstriction. The resultant increased afterload has several adverse sequelae, including metabolic acidosis from tissue ischemia, increased systemic vascular resistance, and decreased cardiac output [32,33]. Reducing afterload in post-CABG patients results in dilation of coronary arteries and reduction of myocardial wall tension and enddiastolic pressures, thereby improving oxygen delivery, decreasing oxygen consumption, and improving cardiac output [2]. Pharmacologic agents, rewarming mechanisms, and mechanical devices can aid in achieving decreased afterload during the immediate postoperative period. Nitroglycerin Vasodilators are the pharmacologic agents of choice to decrease afterload in the immediate postoperative period. Nitroglycerin is a venodilator that offers several benefits to cardiac surgery patients, including coronary artery dilation, prevention of vasospasm, decreased pulmonary
Nitroprusside Nitroprusside is used commonly in cardiac surgery intensive care units because of its potent ability to lower systemic vascular resistance and decrease afterload, thereby increasing cardiac output. In contrast to nitroglycerin, nitroprusside is a potent arterial dilator with fewer venodilator properties than nitroglycerin. Thus, hypertensive patients who have elevated left ventricular filling pressures and marginal cardiac indices benefit from the inherent arterial vasodilatory properties. Because nitroprusside is an effective vasodilator, vigilance must be used during administration to prevent a precipitous drop in mean arterial pressure. Nitroprusside is started, at a dose of 0.3 mg/kg per minute parenterally, and titrated every 10 minutes for blood pressure or cardiac index, to a maximum dose of 10 mg/kg per minute. The onset of action is immediate and effects dissipate rapidly after discontinuation [2,4]. In addition to clinically significant hypotension, side effects of nitroprusside in the cardiac surgery population include coronary steal, cyanide and thiocyanate toxicity, and lactic acidosis [1]. Hydralazine Hydralazine is an intravenously administered direct arterial dilator that causes smooth muscle
MANAGEMENT OF THE POSTOPERATIVE CARDIAC SURGERY PATIENT
relaxation by increasing intracellular levels of cyclic guanosine monophosphate. Because of the profound arterial dilatory effects and minimal venodilator effects of hydralazine, it is an effective afterload reducer. Hydralazine reduces systemic arterial pressures, inducing the baroreceptor reflex, which subsequently causes tachycardia, increased cardiac output, and renin release from heightened sympathetic outflow [34]. Administered at a dose of 5 to 20 mg, hydralazine’s effect on cardiac output can be seen within 15 to 30 minutes and lasts for 2 to 6 hours [4]. With acute administration, side effects include hypotension and reflex tachycardia. Significant adverse reactions associated with chronic administration include fever, neuropathies, vascular headaches, and a lupus-like syndrome that occurs with total daily doses greater than 200 mg [34].
Summary Maintaining adequate cardiac output in postoperative cardiac surgery patients is a complex and challenging feat for health care teams. Alterations in preload, afterload, contractility, heart rate, and rhythm can be devastating to these patients and lead to lethal consequences. An array of pharmacologic therapies is available in the critical care setting to help prevent and treat such complications and ensure satisfactory cardiac performance. References [1] Morris DC, Clements SD Jr, Bailey JM. Management of the patient after cardiac surgery. In: Fuster V, Alexander RW, O’Rourke RA, editors. Hurst’s the heart. 11th edition. New York: McGraw-Hill; 2004. p. 1509–16. [2] Timm C. Cardiogenic shock. In: Crawford MH, editor. Current diagnosis and treatment in cardiology. 2nd edition. New York: McGraw-Hill; 2003. p. 88–96. [3] St. Andre´ AC, DelRossi A. Hemodynamic management of patients in the first 24 hours after cardiac surgery. Crit Care Med 2005;33(9):2082–93. [4] Puyo CA, Lisbon A. Management of the postoperative cardiac surgical patients. In: Irwin RS, Rippe JM, editors. Intensive care medicine. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2003. p. 1637–51. [5] Rudis MI, Dasta JF. Vasopressors and inotropes in shock. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 435–51.
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[6] Albright TN, Zimmerman MA, Selzman CH. Vasopressin in the cardiac surgery intensive care unit. Am J Crit Care 2002;11:326–30. [7] Argenzino M, Chen JM, Choudhri AF, et al. Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg 1998;116:973–80. [8] Levin RL, Degrange MA, Bruno GF. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg 2004;77(2):496–9. [9] Haines ST, Racine E, Zeolla M. Venous thromboembolism. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 337–73. [10] Kimmel SE, Sekeres MA, Berlin JA, et al. Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass. J Am Coll Cardiol 1998;32(7): 1916–22. [11] Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354(4):353–65. [12] Enomoto TM, Thorborg P. Emerging off-label uses for recombinant activated factor VII: grading the evidence. Crit Care Clin 2005;2(3):611–32. [13] Holtzclaw BJ. Shivering in acutely ill vulnerable populations. AACN Clin Issues 2004;15(2): 267–79. [14] Kurz A, Ikeda T, Sessler DI, et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology 1997;86(5):1046–54. [15] Marino PL. Circulatory blood flow. In: Marino PL, editor. The ICU book. 2nd edition. Philadelphia: Lippincott Williams and Wilkins; 1998. p. 3–18. [16] Hollenberg SM, Parrillo JE. Cardiogenic shock. In: Parrillo JE, Dellinger RP, editors. Critical care medicine: principles of diagnosis and management in the adult. 2nd edition. St. Louis (MO): Mosby; 2002. p. 421–36. [17] Johnson-Davis A. Nesiritide therapy for acute heart failure. J Perianesth Nurs 2003;18(6):386–91. [18] Ansell J, Tiarks C, McCue C, et al. Amrinone induced thrombocytopenia. Arch Intern Med 1984; 144(5):949–52. [19] Dasta JF, Kirby MG. Pharmacology and therapeutic use of low-dose dopamine. Pharmacotherapy 1986;6(6):304–10. [20] Lollgen H, Drexler H. Use of inotropes in the critical care setting. Crit Care Med 1990;18(1 Pt 2):S56–60. [21] Raper RF, Cameron G, Walker D, et al. Type B lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25(1):46–51. [22] Totaro RJ, Raper RF. Epinephrine-induced lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25(10):1693–9.
496 [23] Mordes JP, Rossini AA. Lactic acidosis. In: Irwin RS, Rippe JM, editors. Intensive care medicine. 5th edition. Philadelphia: Lippincott Williams and Wilkins; 2003. p. 1186–94. [24] Caruso M, Orszulak TA, Miles JM. Lactic acidosis and insulin resistance associated with epinephrine administration in a patient with non-insulin-dependent diabetes mellitus. Arch Intern Med 1987;147(8):1422–4. [25] Bailey JM, Tanaka KA, Levy JH. Cardiac surgical pharmacology. In: Cohn LH, Edmunds LH Jr, editors. Cardiac surgery in the adult. New York: McGraw-Hill; 2003. p. 85–118. [26] Miller RD. Transfusion therapy. In: Miller RD, editor. Miller’s anesthesia. 6th edition. Philadelphia: Churchill Livingstone; 2005. p. 1799–812. [27] The American Heart Association. Advanced cardiac life support. Circulation 2005;112(22 Suppl 1): III-25–III-54. [28] Bradley D, Creswell LL, Hogue CW Jr, et al. Pharmacologic prophylaxis: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest 2005;128(Suppl 2):39S–47S.
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[29] Kailasam R, Palin CA, Hogue CW Jr. Atrial fibrillation after cardiac surgery: an evidence-based approach to prevention. Semin Cardiothorac Vasc Anesth 2005;9(1):77–85. [30] Bauman JL, Schoen MD. Arrhythmias. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 273–303. [31] The American Heart Association. 2005 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112(24 Suppl 1):IV-1–IV-203. [32] Kuttila K, Niinikoski J. Peripheral perfusion after cardiac surgery. Crit Care Med 1989;17(3): 217–20. [33] Downing SW, Edmunds LH Jr. Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg 1992;54(6):1236–43. [34] Carter BL, Saseen JJ. Hypertension. In: Dipiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: a pathophysiologic approach. 5th edition. New York: McGraw-Hill; 2002. p. 157–83.