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Anesthesia for Cardiovascular Surgery
Section I
Anesthetic Consultation for Adult Cardiovascular Surgery
The principal tasks of the anesthesiologist are to provide relief from pain for patients during operation and to provide optimal operative conditions for surgeons, both in the safest manner possible. To do this, the anesthesiologist must be a competent physician and a clinical pharmacologist, with a broad knowledge of surgery and the ability to utilize and interpret correctly a variety of monitoring devices.
— Dripps, Eckenhoff, and Vandam
Introduction to Anesthesia: The Principles of Safe Practice
Anesthetic management specifically for adult cardiovascular surgery is differentiated from management for general surgery by the high-risk profile and unique perioperative needs of the patient. Despite increasing age and comorbidity, operative mortality has been decreasing in these patients, likely reflective of advances in surgical technique, better management of comorbidity, and advances in monitoring and care by dedicated cardiothoracic anesthesiologists. Furthermore, implementation of evidence-based medical practice to better justify clinical decisions continues to favorably influence patient outcomes.
Preoperative Preparation and Evaluation
Consultation with a cardiothoracic anesthesiologist is essential to optimal preoperative evaluation and management. A thorough history, physical examination, and understanding of the presenting cardiac pathology and proposed surgical procedures are critical. Particular focus should be on areas that may affect perioperative management, such as concomitant patient comorbidity, potential for drug interactions, challenges to airway management and invasive monitoring, as well as acuity of presenting clinical status.
Management of Preoperative Medications
Cardiovascular Medications
Medical management of cardiovascular comorbidity often necessitates extensive pharmacologic support. In general, most antihypertensive and antianginal cardiac medications are continued preoperatively. Whether to continue or when to withhold preoperative antihypertensive therapy requires careful consideration of patient risk/benefit. Acute withdrawal of particular antihypertensive medications such as β-blockers or clonidine may result in considerable perioperative hemodynamic instability; conversely, their continuation results in better hemodynamic stability, antiarrhythmic properties, and improved patient outcome.
Preoperative management decisions to continue angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor subtype I antagonists (ARA) are controversial. Patients in whom ACE therapy was maintained until the morning of surgery had increased probability of hypotension at anesthesia induction. ARA-treated patients had more postinduction hypotension refractory to conventional vasopressors than those on other antihypertensive therapy (β-blockers, calcium channel blockers, or ACE inhibitors) ; thus, some recommend discontinuing ARA before surgery.
Comfere and colleagues examined the relationship between timing of discontinuing chronic ACE inhibitors and ARA and development of hypotension after induction of general anesthesia. Patients receiving chronic ACE inhibitors or ARA therapy less than 10 hours prior to general anesthesia were at elevated risk of developing moderate hypotension within 30 minutes of induction. However, this responded to conventional therapy and was not associated with increased occurrence of postoperative complications.
Hemodynamic instability with continuation of ACE or ARA therapy is not consistent. Licker and colleagues reported that patients treated long term with ACE inhibitors and who had normal left ventricular function did not have altered endocrine response or hemodynamic instability during cardiac surgery. Furthermore, continuing therapy has beneficial effects on the myocardium and kidneys. If it is elected to continue these drugs on the day of surgery, one should recognize that episodic hypotension necessitating vasopressor support may occur.
Thus in general, continuation of preoperative cardiovascular medications is recommended.
Statins
Beyond lipid-lowering properties, statins possess pleiotropic effects that have been reported to reduce postoperative morbidity and mortality. Among patients undergoing percutaneous coronary interventions, Pascual and colleagues reported that statin pretreatment was associated with reduced early ischemic events, primarily in those with high levels of inflammatory markers. Pretreatment with fluvastatin of patients undergoing coronary artery bypass grafting (CABG) reduced P-selectin levels, an adhesion molecule that plays a role in the pathogenesis of arteriosclerosis, below those of patients given a placebo. Berkan and colleagues reported less use of inotropic agents among patients treated with fluvastatin, speculating that myocardial injury caused by cardiopulmonary bypass–induced inflammatory changes was reduced. Others have reported a protective effect of statin pretreatment in reducing myocardial damage after CABG. Based on these beneficial pleiotropic effects, statin therapy should be continued routinely in the perioperative period.
Medications Affecting Hemostasis
Preoperative antiplatelet therapy affects perioperative hemostasis and may contribute to excess bleeding and increased blood product requirements.
Aspirin
In a meta-analysis of preoperative aspirin (ASA) use, Alghamdi and colleagues reported more blood loss and red blood cell (RBC) transfusion, yet similar platelet transfusion and reexploration for bleeding, among patients who received ASA preoperatively. Patients stopping ASA 2 days or less before surgery had higher RBC transfusion requirements than those stopping it more than 7 days preoperatively ; patients discontinuing ASA 3 to 7 days before surgery had little increased requirement for RBC transfusion. Discontinuing ASA 2 to 3 days preoperatively may be sufficient for return of adequate platelet function. Thus, there is little evidence to recommend a preoperative 7-day ASA-free interval.
There are, however, reported benefits to continuing ASA therapy perioperatively. Dacey and colleagues reported that continuation of ASA therapy in isolated CABG was associated with reduced mortality without substantial risk of hemorrhage or blood product requirement. Similarly, Bybee and colleagues reported that preoperative ASA use within 5 days of CABG was associated with lower in-hospital mortality and similar risk of reoperation for bleeding and blood product requirements as in those not receiving preoperative ASA.
Practice guidelines from the Society of Thoracic Surgeons (STS) state that although evidence indicates ASA is beneficial, recent ingestion has been associated with perioperative bleeding. Guideline recommendations are as follows: class IIa recommendation to discontinue ASA 3 to 5 days before elective CABG to reduce bleeding risk; class IIa recommendation for continuation of ASA in urgent and emergency CABG, recognizing that benefits of ASA outweigh the small bleeding risk; and class I to start ASA early postoperatively to take advantage of improved graft patency and mortality benefits.
Clopidogrel
Clopidogrel, an inhibitor of platelet aggregation, works by irreversibly blocking adenosine diphosphate (ADP)-mediated platelet activation. Clopidogrel reduces thrombotic complications following coronary stenting and improves outcomes after acute coronary syndromes. Patients who undergo CABG within 3 to 5 days of clopidogrel treatment are at increased risk for bleeding, RBC requirement, and need for reoperation ( Fig. 4-1 ). Reichert and colleagues examined the effects of a waiting period after clopidogrel treatment before CABG. Patients who received clopidogrel treatment within 72 hours of operation vs. those delayed at least 5 days after clopidogrel treatment had higher transfusion requirements (95% vs. 52%).
Others, however, have reported no increase in bleeding, RBC transfusion, or reexploration for bleeding in CABG patients receiving clopidogrel. Ebrahimi and colleagues examined the effect of clopidogrel in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring CABG in the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. The trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management; 11.1% underwent CABG before discharge. Clopidogrel-exposed patients had longer median duration of hospitalization than nonexposed patients, but experienced fewer ischemic events within 30 days and had similar occurrence of non–CABG-related major bleeding and post-CABG major bleeding. Multivariable analysis demonstrated that clopidogrel use before CABG was a predictor of reduced 30-day composite ischemia.
Combination Antiplatelet Therapy
Cannon and colleagues reported dual antiplatelet therapy within 5 days of CABG was associated with a moderate increase in bleeding; however, combined therapy conferred no appreciable risk for bleeding if discontinued more than 5 days before CABG. ASA and clopidogrel taken together until 2 days before operation is associated with higher postoperative blood loss, but not increased occurrence of reoperation for bleeding. Others report increased blood product requirement with preoperative dual antiplatelet therapy. For patients undergoing off-pump CABG, Shim and colleagues reported that preoperative ASA and clopidogrel exposure even within 2 days of operation did not increase perioperative blood loss and blood transfusion requirements. Of note, the authors used strict transfusion guidelines and intraoperative blood salvage techniques.
Glycoprotein IIb/IIIa Inhibitors
Both short- and long-acting glycoprotein IIb/IIIa inhibitors cause profound platelet dysfunction. In patients requiring emergency operation, they are associated with increased risk for bleeding. Recommendations for discontinuation prior to surgery vary, depending on whether the agent used is a short- or long-acting inhibitor (4 to 6 hours for short acting; 12 to 24 hours for long) ( Table 4-1 ). Lee and colleagues recommend delaying surgery for the appropriate time interval and transfusing platelets as needed rather than prophylactically. De Carlo and colleagues state that emergency surgery can be performed safely in patients treated with all glycoprotein (GP)IIb/IIIa inhibitors, and similarly note that platelet transfusion should be for clinically relevant bleeding. Lincoff and colleagues report that urgent CABG can be performed for abciximab-treated patients without excess mortality or important morbidity.
Table 4-1
Platelet Inhibitors, Mechanism, and Half-Life
Modified from Lee and colleagues.
| Platelet Inhibitor | Mechanism | Half-Life | Minimum Wait |
|---|---|---|---|
| Clopidogrel | ADP-platelet aggregation Irreversible |
8 hours | 5-7 days |
| Abciximab | GPIIb/IIIa Noncompetitive |
30 minutes | 12 hours |
| Tirofiban | GPIIb/IIIa Reversible |
2.2 hours | 4 hours |
| Eptifibatide | GPIIb/IIIa Reversible |
2.5 hours | 4 hours |
Key: ADP, Adenosine 5′-diphosphate; GP, glycoprotein.
Herbal Supplements
Complementary medicine is growing, with 32% to 37% of Americans using herbal supplements in a given year. Herbal supplements are frequently underreported and taken in conjunction with conventional drugs. This results in the potential for herb-drug interactions that may affect absorption and metabolism and/or potentiate or antagonize cardiovascular medications.
There are no clear data on specific herbal-anesthetic interactions, but increased bleeding tendency, cardiovascular instability, and sedation have been associated with their use. Garlic, ginkgo biloba, and ginger possess antiplatelet activity that may increase bleeding risk, particularly for patients on ASA therapy. Garlic inhibits platelet aggregation in a dose-dependent manner. Ginkgo inhibits platelet activating factor; based on pharmacokinetic data and bleeding risk, patients should discontinue ginkgo at least 36 hours preoperatively. Coumarin-containing medications such as chamomile, horse chestnut, motherwort, and tamarind also enhance bleeding risk. In addition to increased bleeding risk, ginkgo biloba has been associated with elevated blood pressure when combined with thiazide diuretics.
Prolongation of anesthesia may result from kava, valerian, and St. John's wort. Kava, an anxiolytic and sedative, may prolong benzodiazepine sedation secondary to its ability to potentiate central nervous system depressants. Concomitant use of opioids with valerian and kava may lead to increased central nervous system depression. Valerian produces dose-dependent sedation, which appears to be mediated through modulation of γ-aminobutyric acid (GABA) neurotransmission. Ginseng may inhibit the analgesic effect of opioids.
Other direct effects of herbal medicines in the operative setting include cardiovascular instability from ephedra (“ma huang”) and hypoglycemia from ginseng. Ephedra contains alkaloids, including ephedrine and pseudoephedrine, that can increase blood pressure and heart rate. Tachyphylaxis may result from long-term use secondary to depletion of endogenous catecholamine stores, which may necessitate use of direct-acting sympathomimetic agents for hypotension. Ginseng may lower postprandial glucose, resulting in hypoglycemia, particularly in fasting patients. Immunosuppressant properties of echinacea theoretically increase risk for poor wound healing and infection. Short-term use of echinacea has immunostimulatory effects that may diminish effectiveness of immunosuppressive medications in the perioperative period.
In general, current recommendations are for patients to discontinue herbal medicines at least 2 weeks before surgery ( Tables 4-2 and 4-3 ).
Table 4-2
Commonly Used Herbal Supplements, Relevant Pharmacologic Effects, and Perioperative Considerations
Modified from Ang-Lee and colleagues.
| Herbal Supplement | Relevant Pharmacologic Effects | Perioperative Considerations |
|---|---|---|
| Echinacea | Activation of cell-mediated immunity | Allergic reactions; decreased effectiveness of immunosuppressants; potential for immunosuppression with long-term use |
| Ephedra (“ma huang”) | Increase in heart rate and blood pressure through direct and indirect sympathomimetic effects | Risk of myocardial infarction and stroke from tachycardia and hypertension; ventricular arrhythmias with halothane; long-term use depletes endogenous catecholamines and may cause intraoperative hemodynamic instability |
| Garlic | Inhibition of platelet aggregation (may be irreversible); increased fibrinolysis; equivocal antihypertensive activity | Potential to increase risk of bleeding, especially when combined with other medications that inhibit platelet aggregation |
| Ginkgo | Inhibition of platelet activating factor | Potential to increase risk for bleeding, especially when combined with other medications that inhibit platelet aggregation |
| Ginseng | Lowers blood glucose; inhibition of platelet aggregation (may be irreversible); increased PT and PTT in animals | Hypoglycemia; potential to increase risk of bleeding |
| Kava | Sedation; anxiolysis | Potential to increase sedative effect of anesthetics; potential for addiction, tolerance, and withdrawal after abstinence unstudied |
| St. John's wort | Inhibition of neurotransmitter reuptake | Induction of cytochrome P450 enzymes, affecting cyclosporine, warfarin, steroids, protease inhibitors, possibly benzodiazepines; decreased serum digoxin levels |
| Valerian | Sedation | Potential to increase sedative effect of anesthetics; benzodiazepine-like acute withdrawal; potential to increase anesthetic requirements with long-term use |
Key: PT, Prothrombin time; PTT, partial thromboplastin time.
Table 4-3
Herbal Supplements and Interactions with Cardiovascular Medicines
Modified from Izzo and colleagues.
| Conventional Medicine | Herbal Supplement | Result of Interaction | Possible Mechanism of Interaction |
|---|---|---|---|
| Interaction with: Digoxin |
Guar gum | Decreased plasma digoxin levels | Reduced absorption; guar gum reduces gastric emptying, which results in transient delayed digoxin absorption |
| St. John's wort | Decreased plasma digoxin concentration | Induction of P-glycoprotein; digoxin is a substrate of P-glycoprotein, which is induced by St. John's wort | |
| Siberian ginseng | Increased plasma digoxin levels | Some component of Siberian ginseng might impair digoxin elimination or interfere with digoxin assay | |
| Wheat bran | Decreased plasma digoxin levels | Reduced absorption; bran contains fibers that can trap digoxin | |
| Interactions with: Antihypertensive drugs |
Ginkgo | Increased blood pressure | Unknown |
| Licorice | Hypokalemia | Additive effect on potassium excretion; licorice has mineralocorticoid effects that may cause potassium excretion | |
| Interactions with: Antiplatelet drugs |
|||
| Ginkgo | Spontaneous hyphema | Additive inhibition of platelet aggregation; ginkgolides have antiplatelet activities and are platelet activating factor receptor antagonists | |
| Interactions with: Anticoagulants |
Boldo/fenugreek | Increased anticoagulant effect | Additive effect on coagulation mechanism; boldo and fenugreek contain anticoagulant coumarin |
| Devil's claw | Increased anticoagulant effect, purpura | Unknown | |
| Garlic | Increased anticoagulant effect; increased clotting time | Additive effect on coagulation mechanisms; garlic has antiplatelet activity | |
| Ginkgo | Reports of intracerebral hemorrhage | Additive effect on coagulation mechanism; ginkgolides from ginkgo have antiplatelet activity and are platelet activating factor receptor antagonists | |
| Green tea | Decreased anticoagulant effect | Pharmacologic antagonism; warfarin produces anticoagulation by inhibiting production of vitamin K–dependent clotting factors; green tea contains vitamin K and thus antagonizes effect of warfarin | |
| St. John's wort | Decreased anticoagulant effect | Hepatic enzyme induction; warfarin is metabolized by CYP1A2 in the liver, which is induced by St. John's wort | |
| Interactions with: Antilipidemic drugs |
|||
| Simvastatin | St. John's wort | Decreased plasma levels simvastatin concentration | Hepatic enzyme induction; simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which is induced by St. John's wort |
| Lovastatin | Oat bran | Decreased lovastatin absorption | Decreased absorption of lovastatin resulted in an increase in LDL levels that led to abortion of trial. Lovastatin pharmacokinetics and LDL returned to normal after bran discontinuation |
Monitoring
Cannulae
In addition to standard American Society of Anesthesiologists monitoring, large-bore intravenous (IV) and brachial or radial arterial cannulae are placed prior to induction of anesthesia. Central venous access is commonly obtained following induction of anesthesia. Decisions about whether to use a central venous triple-lumen catheter vs. a pulmonary artery flotation catheter are case and surgeon/anesthesiologist specific, as is use of ultrasound guidance for placement.
Transesophageal Echocardiography
Transesophageal echocardiography (TEE) is integral to monitoring cardiovascular patients. It is useful in identifying and determining the mechanism of cardiac pathology, can assist with separation from cardiopulmonary bypass (CPB), and may identify unsatisfactory surgical results. In 12,566 consecutive cardiac surgical patients, Eltzschig and colleagues found that TEE influenced surgical decision making in 7% of patients pre-CPB and 2.2% post-CPB. Minhaj and colleagues recommended that TEE be used routinely in all patients undergoing cardiac surgery, because the information provided substantially influences subsequent patient management. They found that TEE demonstrated new cardiac pathology in one of every three patients, and in 3% of patients, it influenced decisions regarding use of CPB. Similarly, Qaddoura and colleagues support use of TEE in primary CABG, noting that it provided new findings pre- and post-CPB in 13% of patients. Early work by Leung and colleagues revealed an association between new and persistent post-CPB wall motion abnormalities and increased risk for postoperative mortality and myocardial infarction.
TEE Doppler-derived hemodynamic indices can provide noninvasive quantitative information on intracardiac velocities, pressure gradients, and valve area. Estimates of forward flow (stroke volume and cardiac output) provide useful information, particularly in cases in which a pulmonary artery flotation catheter is not used ( Fig. 4-2 ). Pulmonary artery systolic pressure can be estimated with use of the modified Bernoulli equation ( Box 4-1 ), which converts instantaneous velocities to pressure gradients. Stroke volume can be calculated as the product of the cross-sectional area and time velocity integral using two-dimensional and Doppler measurements. Figure 4-3 and Box 4-2 illustrate TEE-derived noninvasive calculation of aortic valve area.
Box 4-1
Modified Bernoulli Equation for Calculating Intracardiac Pressure, and an Example
Box 4-2
Modified from Oh and colleagues.
Use of Transesophageal Echocardiography for Noninvasive Calculation of Aortic Valve Area, and an Example
Intraoperative TEE has particular utility and is considered standard of care for patients undergoing mitral valve repair. It allows immediate assessment of reconstructed mitral valves, revealing residual or de novo regurgitation. Whether to intervene for residual mitral regurgitation following repair is controversial. Gillham and colleagues suggest not returning to CPB for a second attempt at mitral valve repair for mild mitral regurgitation based on TEE findings alone. In their investigation, 61% of patients with mild mitral regurgitation identified by intraoperative TEE had zero to trace regurgitation at follow-up transthoracic echocardiography. On the other hand, others have reported a trend toward increased need for reoperation when TEE identifies residual mitral regurgitation following mitral valvuloplasty. TEE is critical in assessing and detecting patients at risk for a rare complication following mitral valve repair: left ventricular outflow obstruction secondary to systolic anterior motion of the anterior mitral valve ( Table 4-4 ). Advances in ultrasound technology with real-time three-dimensional TEE will enhance the ability to image and add to the utility of intraoperative echocardiography in cardiac surgery.
Table 4-4
Echocardiographic Factors Related to Poor Outcome after Mitral Valve Repair for Degenerative Mitral Regurgitation
Modified from Iglesias.
| Pre-CPB | Post-CPB |
|---|---|
| Posterior leaflet height (>15 mm) | Residual mitral regurgitation > mild |
| Anterior leaflet height (>45 mm) | Persistent prolapse |
| Anterior leaflet to posterior leaflet > 1.5 | Increased mean MV pressure gradient |
| Coaptation point of MV leaflets to septum (C-septal) distance < 15 mm | |
| Bileaflet prolapse |
Key: CPB, Cardiopulmonary bypass; MV, mitral valve.
Epiaortic Scanning
Epiaortic scanning may aid surgical decision making. Djaiani and colleagues modify their surgical management in one third of patients based on its results in CABG. Similarly, Rosenberger and colleagues report that it changed epiaortic surgical decision making in 4.1% of patients, including using cardiac arrest, performing aortic atherectomy or replacement, using off-pump support; avoiding aortic clamping; using ventricular fibrillatory arrest; changing arterial cannulation site; and avoiding aortic cannulation.
Cerebral Oximetry
Use of noninvasive measures of regional cerebral oxygen saturation in adult cardiac surgical patients is controversial because there are conflicting data regarding the ability of cerebral oximetry to predict outcomes following cardiac surgery. Hong and colleagues reported cerebral oximetry was not predictive of cognitive decline following heart surgery; however, patients who exhibited intraoperative desaturation required longer postoperative hospitalization. Similarly, Reents and colleagues reported that use of cerebral oximetry was not predictive for postoperative cognitive performance. In contrast, Slater and colleagues reported that intraoperative cerebral oxygen desaturation was associated with increased risk for cognitive decline and prolonged hospital stay after CABG. More data are clearly needed to demonstrate whether complications associated with modifications in patient care are reduced by noninvasive monitoring of regional cerebral oxygenation.
Medications
Premedication
With a majority of patients being admitted the same day as their surgical procedure, preoperative medications for anxiolysis are commonly administered in the preoperative holding area or operating room once the IV cannula is placed. A short-acting sedative such as midazolam is administered in doses of 1 to 2 mg and is preferred over longer-acting agents.
Induction Agents
Propofol (substituted isopropylphenol) and etomidate (a carboxylated imidazole-containing compound) are commonly used induction agents in combination with a low-dose opioid and muscle relaxant, with the goal of facilitated recovery ( Table 4-5 ). Propofol has several properties that make it an advantageous induction agent, particularly for procedures of short duration. It facilitates more rapid awakening compared with other induction drugs, and its antiemetic effects minimize postoperative nausea. Etomidate possesses minimal cardiovascular side effects, making it an ideal agent for induction in hemodynamically unstable patients and those with impaired ventricular function. However, it has a number of side effects, including pain on injection and transient adrenocortical suppression through inhibition of 11-β-hydroxylase. Use of etomidate, particularly in the critical care setting, is controversial because of its adrenal suppression side effects. Ketamine (a phencyclidine derivative) is less commonly used as an induction agent, primarily because of cardiovascular side effects including increases in heart rate and blood pressure, myocardial depression, and episodic emergence delirium. Thiopental is also less commonly used for induction of general anesthesia in cardiac surgery because of less favorable properties. Some centers use high-dose narcotics for induction of anesthesia in cardiovascular patients.
Table 4-5
Induction Agents
Modified from Stoelting (p. 141).
| Drug | Dosage | Mechanism of Action | Systolic Blood Pressure Response | Heart Rate Response |
|---|---|---|---|---|
| Propofol | 1.5-2.5 mg · kg −1 IV | Interaction with GABA | Decreased | Decreased |
| Etomidate | 0.2-0.4 mg · kg −1 IV | Interaction with GABA | No change to decreased | No change |
| Ketamine | 1-2 mg · kg −1 IV | Interaction with NMDA, opioid, monoaminergic, muscarinic receptors and voltage-sensitive calcium channels | Increased | Increased |
| Thiopental | 3-5 mg · kg −1 IV | Interaction with GABA | Decreased | Increased |
Key: GABA, γ-Aminobutyric acid; IV, intravenous; NMDA, N -methyl- d -aspartate.
Maintenance of Anesthesia
The goal of maintenance anesthesia is to maintain stable hemodynamics while allowing for facilitated recovery in a majority of patients. Maintenance of general anesthesia typically consists of a balanced anesthetic technique employing low-dose opioid in combination with a volatile inhalational anesthetic agent or IV agent. The specific choice of opioid, inhalational agent, and muscle relaxant depends on the surgical procedure and patient hemodynamics.
No specific anesthetic maintenance regimen is more advantageous than another in terms of patient outcomes, but evidence supports the potential role of inhalational anesthetic agents in myocardial preconditioning. In a double-blind randomized controlled trial of patients undergoing CABG, Meco and colleagues reported beneficial preconditioning effects of desflurane on myocardial injury (lower troponin I) and myocardial functional recovery following surgery.
Regional anesthesia with or without a general anesthetic has produced mixed patient outcomes. There have been reports of regional anesthetic techniques using epidural blockade in off- and on-pump cardiac surgical patients ; however, regional anesthetic techniques have not been generally adopted.
Opioids
Semisynthetic opioids—fentanyl, sufentanil, and remifentanil—are differentiated by potency, onset, and duration of action. All have demonstrated safety and effectiveness for use in cardiac surgery ( Table 4-6 ). Cheng and colleagues conducted a multicenter randomized controlled trial on the efficacy and resource utilization of remifentanil and fentanyl in fast-track recovery from cardiac surgery. Both anesthetic techniques permitted early and similar times to tracheal extubation, less intense monitoring, and reduced resource utilization after CABG. Similarly, Howie and colleagues compared remifentanil to fentanyl combined with isoflurane/propofol for early extubation following CABG. Both allowed for fast-track cardiac anesthesia. In a randomized clinical trial, Mollhoff and colleagues demonstrated the efficacy and safety of remifentanil and fentanyl for fast-track CABG. Time to extubation was longer, and occurrence of shivering and hypertension were higher in the remifentanil group. However, the groups had similar intensive care unit (ICU) and hospital lengths of stay. Engoren and colleagues compared three opioids used for fast-track cardiac anesthesia: fentanyl, sufentanil, and remifentanil. Extubation times and costs were equivalent. Shorter duration of action of remifentanil allowed for faster recovery, but it is more expensive than fentanyl, and tracheal extubation times were similar.
Table 4-6
Commonly Used Opioids
Modified from Stoelting (p. 83).
| Opioid | Elimination Half-Time (hours) | Effect-Site (Blood-Brain Equilibration [minutes]) | Analgesic Potency |
|---|---|---|---|
| Fentanyl | 3.1-6.6 | 6.8 | 75-125 times more potent than morphine |
| Sufentanil | 2.2-4.6 | 6.2 | 5-10 times more potent than fentanyl |
| Alfentanil | 1.4-1.5 | 1.4 | 1/10-1/5 as potent as fentanyl |
| Remifentanil | 0.17-0.33 | 1.1 | Similar potency to fentanyl |
Antifibrinolytic Drugs
ε-Aminocaproic acid inhibits conversion of plasminogen to plasmin by binding to the lysine binding sites on the plasminogen molecule; tranexamic acid is an alternative antifibrinolytic agent. Lysine analogs have class IA level of evidence indication for use in cardiac surgery to reduce blood loss and transfusion requirements. These drugs play an important role in blood conservation practices in cardiac surgery. Aprotinin, a serine protease inhibitor, is effective in reducing perioperative blood loss but is no longer in use because of a less favorable safety profile.
Heparin Management
Monitoring
Several automated devices are available for anticoagulation management following heparin administration; the activated clotting time (ACT) monitor is the most common. Unfractionated heparin is commonly administered on a weight-based protocol (300-400 units per kilogram) with the goal of achieving an ACT greater than 480 seconds prior to initiation of CPB. In general, if an ACT of 480 or greater has not been achieved with doses of heparin (up to 600 units · kg −1 ), one should suspect heparin resistance.
Heparin Resistance
Reports of heparin resistance in cardiac surgical patients requiring CPB range between 4% and 22%. Chan and colleagues statistically modeled predictors of heparin resistance in 400 patients for elective cardiac surgery. Eight percent met predefined criteria for heparin resistance, defined as a heparin requirement greater than 5 mg · kg −1 to achieve a pre-CPB ACT greater than 400 seconds. Preoperative use of heparin, low-molecular-weight heparin, a platelet count of 300,000 or more, and albumin plasma concentration of 35 g · dL −1 or less were risk factors for heparin resistance.
Treatment options for heparin resistance include fresh frozen plasma administration and antithrombin III therapy, but few randomized clinical trials have addressed the merits of these therapies for treating heparin resistance. In one of the few randomized clinical trials, Avidan and colleagues concluded that antithrombin III was effective in restoring heparin responsiveness for a majority of patients exhibiting heparin resistance prior to CPB (the authors defined heparin resistance as an ACT < 480 seconds after 400 units · kg −1 of heparin). Interestingly, among the 52 patients randomized to antithrombin III, 21% also required fresh frozen plasma.
Heparin-Induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is an immune reaction occurring in 1% to 3% of patients following cardiac surgery. HIT is the most frequent antibody-mediated drug-induced thrombocytopenic disorder. It develops as a result of platelet factor 4–heparin complexes, subsequent platelet activation, and thrombocytopenia following heparin exposure, and is induced by immunoglobulin (Ig)G antibody production. Paradoxically, heparin-induced antibody-mediated activation of platelets and the coagulation system may result in thrombosis. Clinical features may include thrombocytopenia, defined as a 50% or greater reduction in platelet count or decrease to less than 100,000 · dL −1 , thrombosis (50%-70% of patients), and heparin-induced skin lesions (5%-10% of patients). Diagnosis rests on one or more clinical features of thrombocytopenia and thrombosis as well as detection of HIT antibodies.
Guidelines recommend use of unfractionated heparin for patients with a history of HIT who require cardiac surgery and are HIT antibody negative. Repeat exposure to heparin is an option if the prior HIT episode occurs more than 100 days before surgery, because HIT antibodies are transient and generally not regenerative during the brief heparin reexposure. Guidelines also recommend that heparin be restricted to CPB and that alternative anticoagulants be used pre- and postoperatively. For patients with acute HIT—thrombocytopenia and HIT antibody positive—requiring surgery, it is recommended that surgery be delayed until HIT is resolved and antibodies are negative. Alternatively, a non-heparin anticoagulant such as bivalirudin can be used ( Table 4-7 ).
Table 4-7
Alternative Anticoagulants in Patients with Heparin-Induced Thrombocytopenia Requiring Anticoagulation for Cardiopulmonary Bypass
Data from Bojar.
| Drug | Half-Life | Reversal | Metabolism | Monitoring | Dosing |
|---|---|---|---|---|---|
| Bivalirudin | 25 minutes | None | Metabolic > renal | ACT, ECT | 1.5 mg · kg −1 , 50 mg in pump, 2.5 mg · kg −1 · h −1 infusion |
| Lepirudin | 80 minutes | None | Renal | PTT, ECT | 0.25 mg· kg −1 , 0.2 mg· kg −1 in pump prime, 0.5 mg · min −1 infusion |
| Argatroban | 30 minutes | None | Hepatic > renal | PTT, ACT | 0.1 mg · kg −1 bolus, 5-10 µg · kg −1 · min −1 infusion |
| Danaparoid | 20 hours | None | Renal | Factor Xa levels | 125 units · kg −1 , 3 units · kg −1 in pump prime, 7 units · kg −1 · h −1 infusion |
Key: ACT, Activated clotting time; ECT, ecarin clotting time; PTT, partial thromboplastin time.
Heparin Reversal
Following discontinuation of CPB and decannulation, heparin is reversed with protamine sulfate (typically 1 mg of protamine for every 100 units of heparin). Heparin-protamine titration may also be used to provide a more precise amount of protamine to be administered. Protamine administration has well-recognized adverse side effects, from hypotension with rapid administration to anaphylactic and anaphylactoid reactions.
Weaning From Cardiopulmonary Bypass
A number of factors require attention before CPB separation: achieving normothermia, proper electrolyte balance (potassium, glucose, ionized calcium), adequate hemoglobin, anticipation of inotropic and vasopressor support, reestablishing ventilatory support, heart rhythm, and need for pacing. TEE plays an integral role in weaning from CPB, particularly for patients who have undergone valve repair or who have compromised ventricular function. TEE permits rapid recognition in the partial bypass period of circumstances that could complicate separation from CPB, such as persistent valvar regurgitation, intracardiac air, or regional wall motion abnormalities related to graft failure.
Inotropic and Vasopressor Support
Muller and colleagues examined clinical, surgical procedure, and intraoperative factors related to the need for inotropic support following CPB, including previous myocardial infarction, heart failure, higher New York Heart Association functional class, and aortic clamp time. McKinlay and colleagues incorporated information from the intraoperative TEE examination along with demographic and clinical factors to predict the need for inotropic use following separation from CPB. Reoperation, wall motion score index, combined CABG and valve repair or replacement, left ventricular ejection fraction less than 35%, moderate to severe mitral regurgitation, and longer aortic clamp time were risk factors. Ahmed and colleagues added laboratory and hemodynamic factors and identified four risk factors for inotropic requirement: low cardiac index, left ventricular end-diastolic pressure 20 mmHg or higher, left ventricular ejection fraction 40% or lower, and chronic kidney disease stage 3 to 5.
Table 4-8 lists the mechanism of action for commonly used sympathomimetic and vasopressor agents. In addition, milrinone, an inodilator, acts by inhibiting phosphodiesterase III to increase intracellular cyclic adenosine monophosphate levels. Levosimendan, a new calcium sensitizer, possesses vasodilatory and inotropic properties without increasing intracellular calcium concentrations or increasing myocardial oxygen consumption. It acts by inducing a calcium-dependent conformational change of troponin C and enhances both rate and extent of cardiac contraction. Levosimendan has demonstrated utility in facilitating weaning from CPB.
Table 4-8
Sympathomimetics
Modified from Stolting (p. 260).
| Sympathomimetics | α-Receptor | β 1 -Receptor | β 2 -Receptor | Mechanism of Action | Cardiac Output | Heart Rate | Dysrhythmias |  |
Peripheral Vascular Resistance | Renal Blood Flow |
|---|---|---|---|---|---|---|---|---|---|---|
| Natural Catecholamine | ++ | |||||||||
| Epinephrine | + | ++ | ++ | Direct | ++ | ++ | +++ | + | +/− | − |
| Norepinephrine | +++ | ++ | 0 | Direct | − | − | + | +++ | +++ | − |
| Dopamine | ++ | ++ | + | Direct | +++ | + | + | + | + | +++ |
| Synthetic Catecholamine | ||||||||||
| Isoproterenol | 0 | +++ | +++ | +++ | +++ | +++ | +/− | − − | − | |
| Dobutamine | 0 | +++ | 0 | +++ | + | +/− | + | NC | ++ | |
| Synthetic Noncatecholamine | ||||||||||
| Indirect acting: Ephedrine | ++ | + | + | Indirect, some direct | ++ | ++ | ++ | ++ | + | − − |
| Direct acting: Phenylephrine | +++ | 0 | 0 | Direct | − | − | NC | +++ | +++ | − − − |
Key: NC, No change;
, mean arterial pressure.
, mean arterial pressure.
Specific Management Issues
Fast-Track Anesthesia
Early work by Cheng and colleagues was instrumental in establishing a new standard of care for recovery from cardiac surgery by demonstrating the safety and feasibility of facilitated recovery. They tested extubation within 1 to 6 hours vs. conventional tracheal extubation within 12 to 22 hours after CABG in a randomized clinical trial. Post-extubation intrapulmonary shunt fraction improved and ICU and hospital lengths of stay were shorter, without increased morbidity. Similarly, Reis and colleagues reported that fast-track and ultra–fast-track (extubated on ICU arrival) anesthesia were not associated with increased patient morbidity and mortality following CABG. In off-pump CABG, Djaiani and colleagues reported facilitated operating room extubation, lower nurse-to-patient ratio, and earlier patient discharge without need for reintubation with ultra–fast-track anesthetic techniques. Risk factors for delayed extubation of patients planned for fast-track anesthesia are advanced age, female gender, postoperative use of intraaortic balloon pumping, inotropes, and postoperative bleeding and atrial arrhythmias.
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