Anesthesiology

Heart transplantation

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What the Anesthesiologist Should Know before the Operative Procedure

Once diagnosed with end-stage cardiomyopathy, prognosis and survival is very poor. These patients are often critically ill, and may have different underlying processes that led to their end-stage disease (primary, ischemic, valvular, congenital, etc.). Fortunately, heart transplantation has become an option to improve survival for a select few with this illness.

When presenting for heart transplantation, the anesthesiologist should be aware of the patient's etiology of disease, baseline function, and current symptoms. They are likely to have extremely poor ejection fractions, and many are placed on inotropic support for long-term use. While awaiting a donor organ, these patients may have received a ventricular assist device (VAD) as a "bridge to transplantation." Often, they are anticoagulated, either due to the presence of a VAD or thrombus formation. Patient comorbidities, such as pulmonary hypertension, volume overload, renal disease, arrhythmias, and anxiety, are frequently related to their heart disease.

Along with anesthetic management of these patients, being aware of the timing involved in heart transplantation is also important. Prolonged ischemic time of the donor organ can result in decreased cardiac function and poor outcome after transplantation. Therefore, preoperative evaluations are time-limited. The anesthesiologist also plays a key role in the surgery by being aware of and being able to successfully treat common immediate postoperative complications such as right ventricular failure and bleeding.

If the anesthesiologist has a comprehensive understanding of the perioperative management, including the disease process, comorbidities, logistics, and critical issues of the operation, it will certainly contribute to improved outcomes for the heart transplant recipient.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

Although heart transplant recipients are often critically ill, these patients are being treated for a chronic condition, and therefore, they have been managed with pharmacologic support and/or with assist device support for long periods of time. Most will arrive to the operating room in a fairly stable condition.

Occasionally, patients will be considered more "urgent" based on a recent deterioration of their condition that increased their transplant status. Despite the overall stability of these patients with a chronic disease, surgery is still considered emergent. This is generally based on the donor organ, and not the recipient patient, because of the limited number of donor organs available. Once the donor heart has been procured, there is limited time for obtaining additional preoperative information for the recipient, with the major risk being a delay that causes an increased period of ischemia for the donor organ.

  1. Emergent - Given that all heart transplantations are considered emergent, the goals are to prepare the recipient in a timely fashion so surgery can proceed without extending donor ischemic time. Ideally, the ischemic period is four hours or less. Since these patients are not scheduled for surgery, they may present with full stomachs. They may also be fully anticoagulated if on a ventricular assist device or if known to have intra-cardiac thrombus.

  2. Urgent - Differentiating between emergent and urgent surgery in this situation is difficult. As noted, these patients are fairly stable, and thus not receiving an organ does not impose an immediate life-threatening problem. However, the surgery must proceed quickly so the donor organ does not suffer. Issues with urgent surgery are similar to those described above for emergent procedures.

  3. Elective - Given the limited availability of donor organs, these cases are not considered elective.

2. Preoperative evaluation

One cannot predict when a donor organ will become available for a heart transplant candidate. Thus these cases generally do not provide the anesthesiologist with much time for a full preoperative evaluation as may be performed for most cardiac surgery patients. Fortunately, these patients are followed by a group of physicians involved in their medical care, and much of the preoperative work-up has been completed prior to their potential surgery.

Like the preoperative evaluation of any patient receiving an anesthetic, questions regarding last oral intake, allergies, surgical and anesthetic history, and an airway evaluation should be completed. The patient's medical record should be reviewed along with recent labs, electrocardiograms, and imaging studies. A recent echocardiogram would be useful to know baseline cardiac function. Current medications, infusions, and mechanical support devices should be noted.

A focused history should include a review of current symptoms and baseline activity level, and a physical exam should evaluate all relevant systems. Certain features to look for during the evaluation include pulmonary and peripheral edema. Changes in shortness of breath or visible peripheral swelling as noted by the patient can provide information regarding changes in function and degree of volume overload.

There are very few medical conditions directly related to the recipient that warrant delaying or cancelling surgery. As mentioned previously, delay of surgery increases ischemic time for the donor organ. Often if there is a condition that is causing the patient to be unstable, it is related to deteriorating cardiac function, which would further emphasize the need for heart transplantation.

If a patient has any signs of infection on initial presentation to the hospital (e.g., fever or elevated white blood cell count without a known cause), then another potential recipient may be sought after for receiving the donor organ. A recurrence of or new diagnosis of active malignancy is likely to temporarily remove the patient from the transplant list until further work-up can be completed. Concerns regarding irreversible pulmonary hypertension, a contraindication to transplant, would likely have been addressed during work-up for heart transplantation.

3. What are the implications of co-existing disease on perioperative care?

Given their critical illness, it is not surprising that end-stage heart failure patients have multiple other comorbidities. These co-existing conditions can have a significant impact on perioperative management and postoperative outcomes. It is imperative to review the patient's entire history prior to induction of anesthesia and to be aware of the options for managing and treating various associated conditions. Disease processes by system are further reviewed in detail below.

b. Cardiovascular system

Of course, cardiomyopathy is the reason these patients are coming to the operating room, but co-existing cardiovascular disease is often present, along with their primary cardiomyopathy. Management of the primary cardiomyopathy is described in the subsequent sections, but goals are to maintain hemodynamic stability, with the use of inotropes or mechanical circulatory support until cardiopulmonary bypass is initiated. These patients may have pulmonary hypertension and systemic vasodilation, which often requires pharmacologic treatment. The use of invasive hemodynamic monitoring and transesophageal echocardiography can aid in preload and afterload management.

Given their increased risk of ventricular arrhythmias, these patients often have automatic implantable cardioverter defibrillators placed. The defibrillating function should be deactivated to prevent electrocautery interference once the surgery has started. If a redo sternotomy patient does not have a defibrillator, then defibrillator pads should be placed on the patient in the event of an arrhythmia occurring during initial exposure. Also, it is not uncommon for these patients to have implanted pacemakers due to atrial fibrillation or other conduction abnormalities. If the patient is pacer-dependent, appropriate pacing modes should be activated to again not allow for unintended inhibition.

c. Pulmonary

Despite being treated with diuretic therapy, patients with end-stage heart failure often continue to have symptomatic pulmonary edema. The degree of edema and congestion can be noted on preoperative chest x-ray. With heart failure and elevated pulmonary artery pressures, it is not uncommon to hear of complaints of shortness of breath and inability to tolerate lying flat. Ensuring patient comfort, with the head of the bed raised, may improve respiratory function, as well as help alleviate patient anxiety due to distress. If volume overload is suspected, additional intraoperative diuresis may be needed. Decreasing pulmonary vascular resistance with inhaled vasodilators is also indicated if starting pulmonary pressures are significantly elevated.

d. Renal-GI:

Chronic end-organ hypoperfusion in patients with a longstanding cardiomyopathy often leads to some degree of renal dysfunction, as well as visceral and splanchnic malperfusion. Along with hypoperfusion, venous congestion may lead to hepatic dysfunction and mild elevations of liver enzymes. This may be manifested as an increased risk of coagulopathy during transplant surgery. Activation of the renin-angiotensin-aldosterone system can also lead to volume overload and sodium retention, which may need to be addressed perioperatively with additional diuresis.

e. Neurologic:

Candidates for heart transplantation often suffer multiple comorbidities, and their chronic illnesses often lead to some degree of depression and anxiety. It is not uncommon for many of these patients to be taking benzodiazepines preoperatively. In the perioperative period, the anesthesiologist is faced with relieving the patient's fears and additional stress of anticipated surgery. When using sedatives, care must be taken to not cause excess myocardial or respiratory depression in these patients with limited reserve.

Pre-existing cerebrovascular disease tends to be of greater concern for the postoperative period when neurologic function is assessed. Heart transplant candidates may also present with carotid stenosis, which can require higher mean arterial pressures for adequate cerebral perfusion. In certain instances, carotid endarterectomy is performed shortly after the patient is listed for a transplant in an effort to reduce postoperative cerebrovascular events.

f. Endocrine:

Brittle diabetes was once considered a contraindication to heart transplantation. However, diabetics without signs of end-organ damage are now being transplanted routinely. Of concern in the perioperative setting, is the potential for increasing insulin requirements due to the additional hyperglycemia that comes with steroid administration (included in the routine immunosuppressant regimen given to all transplant recipients).

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. muscoloskeletal in orthopedic procedures, hematologic in a cancer patient)

Hematologic

Many patients with this chronic disease have some degree of anemia. Further decreases in hemoglobin levels intraoperatively due to blood loss may not be tolerated well, and this may be noted by decreases in mixed venous oxygen saturation. Maintaining adequate levels may require the use of blood products, which should be screened thoroughly for ABO-Rh compatibility, as well as Cytomegalovirus (CMV)-negative status if indicated.

4. What are the patient's medications and how should they be managed in the perioperative period?

Patients with end-stage heart failure are started on an aggressive regimen of conventional therapies to optimize their cardiac function. Goals are to maximize cardiac output, decrease afterload, and reduce the degree of volume overload. Common medications given to heart failure patients include positive inotropes, beta-blockers, vasodilators, and diuretics. Inotropes such as dobutamine or milrinone may be used to augment contractility. Vasodilators such as angiotensin-converting enzyme (ACE) inhibitors are taken for preload and afterload reduction. Diuretics include potassium-sparing and loop diuretics to decrease water retention. Many patients may also be taking antiplatelet agents for significant coronary or peripheral vascular disease.

There is debate regarding the continuation of ACE-inhibitors prior to surgery due to the concern of vasoplegia, hypotension, and increased pressor requirements; however, more recent data suggests far less harm, and perhaps, benefit from use. Given that heart transplantation procedures are not electively scheduled operations, many patients are given very short notice about their surgery, and they may have already taken their oral medications including ACE-inhibitors. Therefore, it is difficult to modify pre-surgery oral medications. As for intravenous (IV) medications such as inotrope infusions, these should be continued preoperatively and intraoperatively as the donor organ is being procured. Inotropes are generally continued, and often escalated after induction of anesthesia, to maintain cardiac output until cardiopulmonary bypass has been instituted.

Anticoagulation is also common in patients with cardiomyopathies due to the high risk of thrombus formation and high incidence of atrial fibrillation. Many of these patients are on warfarin preoperatively. Again noting the timing of heart transplants, it is not feasible to stop oral anticoagulants days before surgery. If the patient is admitted to the hospital, he or she may be placed on a heparin infusion. The presence of a ventricular assist device (VAD) warrants anticoagulation as well, to prevent clot formation within the VAD. If the patient is on a heparin infusion preoperatively, then it should be continued when arriving to the operating room. The exact time of when to discontinue heparin can vary, but generally, it is often stopped around the time of induction of anesthesia.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

As noted above, candidates for heart transplantation are commonly on multiple medications to optimize their cardiac status. Those of particular concern during the perioperative period include inotropes and anticoagulants. Sedation and general anesthesia may contribute to myocardial depression, which is problematic in these patients with end-stage heart disease. Maintaining inotrope infusions and augmenting as needed is important for achieving stable hemodynamics. Patients on prior anticoagulation, either by oral warfarin or intravenous heparin, add an additional bleeding risk to the surgery. Obtaining initial exposure for cardiectomy may be challenging for the surgeon, and closing the chest at the end of the procedure may be difficult with a marked coagulopathy. For this reason, fresh frozen plasma should be available.

Other medications that are commonly seen in the perioperative period include a few drugs that are new to the patient. These are generally not taken chronically, and they include steroids, immunosuppressants, and prophylactic antibiotics. A one-time dose of steroids is frequently administered intraoperatively, and immunosuppressants are often dosed at the start of the surgery. The choice of drugs can vary, but it is extremely important that the appropriate regimen is given to prevent rejection. The preoperative antibiotics are discussed below.

i. What should be recommended with regard to continuation of medications taken chronically?

Holding or adjusting medications that are taken chronically is often not possible in heart transplantation. These patients are not aware of when a potential donor organ becomes available until only a few hours before their proposed surgery. If the patient had been started on an inotrope for long-term use, this medication should be continued in the perioperative period.

j. How to modify care for patients with known allergies -

As with any other surgery requiring an anesthetic, patient allergies will modify the choice of drugs, monitoring equipment, and operating room supplies. Alternative agents should be used for narcotics, sedative-hypnotics, and muscle relaxants as appropriate. Specific attention should be paid to substitute antibiotic regimens because of the importance of preventing infection in the soon-to-be immunocompromised heart transplant patient. Latex-free monitoring devices should be used in the case of a latex allergy. Tape and adhesive sensitivities should be addressed with alternative options.

k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

There are several products in the operating room that contain latex. Patient sensitivity to latex (e.g., rash or itching) warrants the use of latex-free products, such as latex-free gloves and a latex-free foley catheter. Most airway equipment is now generally latex-free, but certain reservoir bags on the anesthesia machine continue to contain latex, making the entire breathing circuit not truly latex-free. Tourniquets used for intravenous (IV( line placement are also often made of latex, as well as certain ports on IV lines and tubing.

These items should all be switched to latex-free products. If there is any concern about a larger reaction to latex, including anaphylaxis, then further preparations need to be made, and they should be completed prior to patient arrival in the operating room. Specific to the patient undergoing heart transplantation, a pulmonary artery catheter (PAC) that does not contain latex should be available. Some may continue to use a standard latex-containing PAC if the reaction is a localized rash or if the reaction has not been confirmed, but most will err on the safe side by using a latex-free PAC if there is any uncertainty of the reaction.

l. Does the patient have any antibiotic allergies- - Common antibiotic allergies and alternative antibiotics]

The prevention of infection is paramount in heart transplant recipients because of their post-operative immunosuppressed status. Therefore, it is also important to assess patient antibiotic allergies preoperatively so appropriate prophylactic antibiotics can be administered. Please see below for recommendations regarding specific antibiotic regimens and reasons for their selection.

As for allergies to common perioperative antibiotics, penicillins account for the highest rates of allergic reactions. Given the low cross-sensitivity, cephalosporins may still be administered in the penicillin-allergic patient if the reaction is mild or non-systemic (e.g., localized rash). However, with true penicillin allergies, cephalosporins are generally avoided. Alternative options include clindamycin or vancomycin. Vancomycin allergies are rare, and reactions are often related to rapid administration rather than true allergy.

m. Does the patient have a history of allergy to anesthesia?

If the patient has a history of or susceptibility to malignant hyperthermia (MH), then MH precautions should be taken for the anesthetic. Avoid all triggering agents including the volatile anesthetics and depolarizing neuromuscular blockers (i.e., succinylcholine). Assure that the entire breathing circuit, including the absorbent, has been changed, and that the anesthesia machine has been thoroughly flushed. The anesthetic plan typically consists of a total IV anesthetic (TIVA) using non-triggering agents. A fully stocked MH cart, including dantrolene, should always be readily available. If there is any suspicion of MH intraoperatively, pre-existing MH protocols for management should be followed.

Other risk factors for MH include a family history of MH without the appropriate negative testing in the patient, as well as a history of certain myopathies. These patients should also receive a non-triggering anesthetic with all of the appropriate precautions.

Allergies to local anesthetics are rare and generally due to agents from the ester group. Patients with this allergy are often sensitive to an ester local anesthetic metabolite, specifically para-aminobenzoic acid (PABA). Since the amide group of local anesthetics undergoes a different form of metabolism, there is no cross-allergy, and therefore amides are safe to use in patients with ester allergies. The most common allergy to an anesthetic is from muscle relaxants, or neuromuscular blocking drugs (NMBDs). If a patient has a documented allergy to a muscle relaxant, then all NMBDs should be avoided due to the potential for cross-reactivity, and an anesthetic plan without NMBDs should be utilized unless a negative skin test has been obtained for a particular drug.

5. What laboratory tests should be obtained and has everything been reviewed?

  1. Hemoglobin levels: It is common for patients with cardiomyopathies to be anemic. Therefore, it is important to know baseline hemoglobin and hematocrit values. This can provide information regarding their baseline oxygen-carrying capacity, and it may also serve as a predictor of risk of transfusion. Decisions to transfuse or prime the bypass circuit with packed red blood cells can be made on initial values, since estimated dilutional levels can be calculated based on crystalloid infused and the crystalloid volume of the pump prime. Goals during bypass are to maintain a hematocrit value between 25 and 30%.

  2. Platelet count: Preoperative platelet count has been shown to be a predictive factor for post-cardiopulmonary bypass platelet count. Knowing that bypass contributes to varying degrees of platelet dysfunction, a low baseline value may assist in the decision to order platelets for transfusion after bypass, especially if the patient was on an antiplatelet agent preoperatively.

  3. Coagulation panel: Having a baseline coagulation panel provides information regarding risk of bleeding. If the patient was anticoagulated preoperatively, then any remaining effects of the medication can be seen. If the patient has an elevated partial thromboplastin time or prothrombin time without any anticoagulation preoperatively, then this may indicate potential liver dysfunction. Given the risk of bleeding in these operations, these values can again aid in the decision to transfuse fresh frozen plasma.

  4. Electrolytes: Preoperative assessment of electrolytes can assist in determining volume status (dehydration versus euvolemia). Creatinine levels can indicate baseline renal function, which is important to know for medications with primarily renal clearance. If the patient is on diuretics, sodium and potassium levels should be noted. A low potassium level is also important to treat in patients on preoperative digitalis.

  5. Type and screen: One of the crucial elements in deciding whether a particular donor is suitable for a particular heart transplant recipient is ABO blood group compatibility. This is generally done prior to scheduling the surgery; however, it is imperative that the perioperative team verifies a match in order to prevent early rejection of the transplanted organ.

  6. Imaging/other tests: A chest x-ray should be reviewed for signs of hyperinflation (suggesting obstructive disease) or pulmonary edema (heart failure). Conduction abnormalities can be assessed with a preoperative electrocardiogram. A recent echocardiogram is of value to know biventricular function, ejection fraction, and valvular function. It is also of importance in the patient on mechanical circulatory support, since positioning and function of the device can be assessed. A right heart catheterization, if available, can provide baseline pulmonary artery pressures. This can be useful for predicting the amount of right ventricular support that may be needed for the new organ.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

The primary anesthetic for heart transplantation is general endotracheal anesthesia with inhalational maintenance. The use of regional anesthesia with a thoracic epidural has been described as an adjunct to general anesthesia, but it is not used as the primary anesthetic. Monitored anesthesia care is not an option for these complex cases.

Regional anesthesia

The use of regional anesthesia (high thoracic epidural) has been previously described as an adjunct to general anesthesia (GA). Epidural use as a primary anesthetic (i.e., awake patient) has been shown to be feasible; however, this is truly experimental due to many concerns regarding patient safety and is thus not recommended.

When combined with GA, epidural anesthesia is primarily used for postoperative analgesia and attenuation of the stress response. Several studies have cited potential benefits with thoracic epidural anesthesia, particularly improved analgesia and earlier tracheal extubation. There is controversy to any further benefit beyond this, since studies have shown no difference in pulmonary and cardiac function when compared to patients who did not receive an epidural. Epidural use is further limited by concern regarding placement in the potentially anticoagulated heart transplant candidate, which may lead to epidural hematoma. Also, many of these patients have such poor cardiac function that they may not tolerate even a mild sympathectomy. Therefore, regional anesthesia with epidural is at this time an uncommon technique.

General anesthesia

General anesthesia with an endotracheal tube is the standard anesthetic for heart transplantation. Induction technique can vary, taking into consideration the possible need for a rapid-sequence intubation in the patient with a full stomach.

The advantage of having an endotracheal tube in place allows for a secure airway, which is of particular importance in the patient at risk for aspiration. It also allows for the ability to control tidal volumes and hold ventilation as needed during surgical exposure, the application of positive end-expiratory pressure, and bronchoscopy if needed for any pulmonary concerns. Since these patients frequently need additional time for monitoring of hemodynamic stability and control of bleeding while in the intensive care unit, having an intubated patient allows for emergent procedures in the immediate postoperative period. Intraoperatively, having a secure airway throughout the procedure also allows for continuous transesophageal echocardiography.

Specific induction and maintenance techniques are described below. In general, the goals of induction are to maintain hemodynamic stability with IV agents. Maintenance is often an inhalational anesthetic with IV narcotics. The goals are again to maintain stability and adjust inotropic support as necessary, until cardiopulmonary bypass is initiated.

Monitored anesthesia care

Given the complexity of the heart transplantation procedure, the use of monitored anesthesia care (MAC) is not a standard option for this surgery. Light sedation may be used for placement of invasive monitors (e.g., central line placement), if done prior to induction of general anesthesia.

6. What is the author's preferred method of anesthesia technique and why?

What does the typical intraoperative course involve?

In preparing our patients for heart transplantation, our institutional preference is to have the patient enter the operating room at a time decided by the transplant team based on patient factors and donor site. This is often when the procurement team has already departed to the donor site. While awaiting the decision on the donor organ, invasive lines are placed with light sedation (midazolam +/- fentanyl). A radial arterial catheter is placed, followed by a central venous and pulmonary artery catheter. Our preference is to use the left internal jugular vein to preserve the right neck for future endomyocardial biopsy access. However, if the patient has a left-sided defibrillator or pacemaker, the right internal jugular vein is used. Full sterile technique is employed for all invasive lines, and local anesthetic is infiltrated prior to each procedure.

When the procurement team has had the opportunity to inspect the donor organ, they call into the operating room to make us aware if the surgery will proceed or not. If the donor organ is not suitable for the patient, he or she is informed, and all invasive lines are removed prior to leaving the operating room. If the donor organ is suitable for our patient, we then induce general anesthesia, taking into consideration the patient's last oral intake and keeping in mind the patient's limited cardiac function.

While some may have a preference for a particular induction agent due to decreased myocardial effects, the choice of drug is not as important as the maintenance of hemodynamic stability throughout the induction period. Often, a high-dose narcotic induction, with a neuromuscular blocking drug, and with or without a low dose of sedative-hypnotic agent, can be used to achieve the goals. Maintenance is with an inhalational anesthetic, supplementing with narcotics as needed. Epidural anesthesia is not a standard practice at our institution, for the reasons noted in a previous section.

Along with invasive hemodynamics, standard monitors including 5-lead electrocardiogram, pulse oximetry, capnography, and nasal and bladder temperature are monitored. If the patient was on an inotrope preoperatively, it is continued in the operating room and now increased if necessary due to the effects of general anesthesia. Preoperative antibiotics (see below) and immunosuppressants are administered, along with a bolus dose and infusion of an antifibrinolytic if not contraindicated. All IV access lines placed prior to operating room arrival are removed (other devices removed by surgeon at end of surgery). Transesophageal echocardiography (TEE), if not contraindicated, is used for all transplant recipients. Its value in the pre-bypass period is notable for identifying intra-cardiac thrombus, ruling out significant aortic atheroma, and calculating pulmonary pressures.

While waiting for the donor organ to arrive, the surgeons proceed with exposure of the native heart. Bypass is instituted, but cardiectomy is not performed until the donor organ is in the operating room. With this arrangement, ischemic time for the donor organ is minimized. Heart transplantation then follows using one of the techniques described below. Our pulmonary artery catheter is generally placed in the pulmonary artery while the native heart is in place, withdrawn for cardiectomy, and then re-advanced when the transplanted heart is filled.

Having reviewed the patient's history and having baseline hemodynamics regarding pulmonary pressures, we anticipate potential dysfunction of the donor right ventricle and prepare in advance with pulmonary vasodilators and the use of inotropes, which are started before terminating bypass. Epicardial pacing is initiated, with or without isoproterenol, to maintain a rate of 100 to 110 beats per minute. Managing other potential complications, including coagulopathy, is described below. TEE is again used for verifying removal of intra-cardiac air prior to coming off of bypass and to assess ventricular and valvular function of the new heart. Once off of bypass, the integrity of surgical anastomoses, as well as unobstructed caval and pulmonary vein flow, can be verified.

After heparin reversal with protamine, bleeding risk is assessed and blood products are transfused as necessary. Ventricular function and hemodynamics are re-evaluated after chest closure. If the patient remains stable, transport to the intensive care unit takes place while sedated and intubated.

What prophylactic antibiotics should be administered?

The prophylactic antibiotic regimen is often very specific for heart transplant recipients, and infection prevention is a major goal for these immunosuppressed patients. The choice of drugs is often coordinated with a Transplant Coordinator who is aware of the infectious status of the donor and the recipient.

Generally, antibiotics are also chosen based on institution-specific resistance rates and common pathogens. Skin organisms, like Staphylococci and Streptococci, are of primary concern in antibiotic prophylaxis. Cephalosporins, such as cefazolin, are frequently chosen for coverage of many gram-positive and gram-negative bacteria. Third-generation fluoroquinolones may be substituted in the penicillin-allergic patient. Due to increasing institutional prevalence of methicillin-resistant staphylococcus aureus (MRSA), it is also common to see vancomycin as an additional agent in the antibiotic regimen. Pneumonia is a common infection in the postoperative period, and therefore preoperative sputum cultures may dictate the need for additional antibiotic coverage.

What do I need to know about the surgical technique to optimize my anesthetic care? What can I do intraoperatively to assist the surgeon and optimize patient care?

There are different surgical techniques utilized for heart transplantation. The decision on which to choose is based on patient factors; however, surgeon preference also plays a role. Each involves a sternotomy, aortic and venous cannulation, followed by cardiopulmonary bypass (CPB).

  1. Orthotopic heart transplantation: In this technique, the patient's native heart is completely removed (cardiectomy) except for atrial cuffs. This occurs after CPB is initiated. Two methods can be used for native cardiectomy. The biatrial method involves leaving behind a left atrial cuff that contains the four pulmonary veins, as well as a portion of the right atrium. Both atrial cuffs are then sutured to the donor heart before the aortic and pulmonary artery anastomoses are completed. The bicaval method involves a similar left atrial cuff; however, the native right atrium is completely removed. In this method, cavoatrial anastomoses replace the right atrial suture line.

It has been noted that the bicaval method results in fewer conduction abnormalities and decreased tricuspid regurgitation. Either method requires that the anesthesiologist be aware of the stage of the procedure, since the pulmonary artery catheter will need to be withdrawn the appropriate distance prior to native cardiectomy.

  1. Heterotopic heart transplantation: Heterotopic heart transplantation is very rare. In this technique, the recipient's native heart is left in place and the donor heart is placed in the right anterior chest. With the use of conduits as needed, the donor and native right ventricles pump blood into the pulmonary artery, while both the donor and native left ventricles pump blood into the aorta. Common indications for this parallel circulation include a size mismatch between the donor and recipient, as well as severe pulmonary hypertension in the recipient. In the latter case, the native right ventricle is more accustomed to working with high pulmonary pressures, making the donor right ventricle less likely to fail.

After all anastomoses have been completed, the aortic cross clamp is removed. The new heart is reperfused, and the patient is weaned off of cardiopulmonary bypass with pacing and pharmacologic support as needed. Anesthetic implications for each of the surgical techniques are similar to those for any patient undergoing CPB: general anesthesia with appropriate hemodynamic monitoring and support. If the patient is having a "redo" operation (i.e., prior sternotomy) or is anticoagulated, the anesthesiologist may consider using blood products early to help minimize bleeding risk.

If there are no contraindications, the use of transesophageal echocardiography (TEE) can assist the anesthesiologist in determining preoperative inotropic support and postoperative cardiac function. TEE can also assist the surgeon in wire or cannula placement. If the patient had prior placement of a defibrillator or pacemaker, then it will be explanted at the end of the operation. It is important that the defibrillator function is deactivated prior to surgery (due to potential electrocautery interference) and that an external pacemaker is available should it be needed after transplantation.

Intraoperatively, the anesthesiologist may be asked to provide controlled hypotension for certain periods of cannulation and anastomoses. It is important to keep in mind end-organ perfusion and maintain periods as brief as needed to accomplish the surgical goals. Frequent monitoring of arterial blood gases and electrolytes should be performed to maintain adequate hematocrit levels while on CPB. Cell saver is routinely used during cardiac surgery and it should be available after heparinization.

Electrolytes, particularly potassium, should be managed in conjunction with the perfusionist, if there are multiple periods of high-dose cardioplegia solution being used. Insulin infusion should be instituted for glycemic control. Current recommendations on goal blood glucose levels seem to vary, but most will aim for near normoglycemia in the perioperative period. As mentioned above, TEE guidance can help optimize patient care as inotropic support can be adjusted based on findings pre- and post-CPB. Also, evaluation of cardiac function, the integrity of anastomoses, and chamber filling can be evaluated post-CPB.

What are the most common intraoperative complications and how can they be avoided/treated?

The most common intraoperative complications generally occur either when weaning from CPB or in the immediate post-CPB period. One of the most common reasons for not being able to wean off of bypass is right ventricular failure. This typically results from the patient having high pulmonary vascular resistance (PVR) preoperatively and the donor right ventricle not being accustomed to such high afterload. If pulmonary hypertension is noted at the start of surgery, one can preemptively institute additional inotropic support for the right ventricle. Milrinone is a commonly used agent, although one has to be aware its vasodilating properties.

Maintaining a high inspired oxygen concentration, preventing hypercarbia, and treating acidosis can also assist in decreasing pulmonary pressures. Inhaled agents are also beneficial in acting as selective pulmonary vasodilators. Common agents include nitric oxide and the prostacyclin, epoprostenol. High PVR is not the only reason for right ventricular dysfunction. Air embolism to the right coronary or a prolonged ischemic time may contribute to decreased function, which can be treated with additional reperfusion time and more inotropic support. In rare cases, mechanical circulatory support may be temporarily needed.

Excessive bleeding may also complicate the immediate post-bypass period. If the patient was anticoagulated preoperatively, one can anticipate that fresh frozen plasma will be needed. The perioperative use of antifibrinolytics when not contraindicated can assist in decreasing the overall bleeding, and several studies have confirmed their beneficial effects. Patients with a prolonged bypass period may also have increased platelet destruction and/or dysfunction. Early administration of platelets after bypass is also warranted in these situations. Of course, a surgical bleeding source should always be ruled out, but ongoing coagulopathy may require cryoprecipitate, and in certain instances, the cautious use of recombinant factor VII. If stat intraoperative laboratory tests can be obtained, it would be helpful to obtain a coagulation profile. The use of thromboelastography, if available, can also assist in transfusion management.

Rhythm disturbances are occasionally encountered after heart transplantation. The denervated heart may require epicardial pacing, along with a beta-agonist such as isoproterenol. In rare circumstances, the patient will require a postoperative permanent pacemaker. Left ventricular dysfunction is also a concern post-bypass. This is frequently seen in cases of prolonged ischemic time of the donor organ or inadequate perfusion. Additional inotropic support can be used, along with a possible assist device until function can gradually recover.

A very rare complication that may be seen intraoperatively is hyperacute rejection. This is due to a complement-mediated response that takes place in patients with pre-existing antibodies. The newly transplanted organ will show signs of severe failure, and the patient will need an assist device until a new organ is available.

a. Neurologic

N/A

b. If the patient is intubated, are there any special criteria for extubation?

While some institutions may advocate for extubation in the operating room (OR) for certain cardiac procedures (e.g., minimally invasive, technically smooth operation without complications, normal cardiac function), routine extubation after heart transplantation is not common. These patients are generally transported to the intensive care unit (ICU) intubated and sedated.

Concerns regarding right ventricular failure, coagulopathy, patient body temperature, pulmonary function, and unstable hemodynamics often dictate that the patient be initially monitored for a brief period of time in the ICU. Early extubation may still take place as soon as the patient demonstrates hemodynamic stability, is awake and alert, and possesses adequate strength.

c. Postoperative management

What analgesic modalities can I implement?

Heart transplant recipients generally remain intubated in the immediate postoperative period. Therefore, initial analgesia must come in the IV form. Often a narcotic infusion is started in the intensive care unit. A benzodiazepine infusion may also be added for amnestic purposes. When ventilator weaning has begun or when the patient has been extubated, IV narcotics can be continued with patient-controlled analgesia, allowing the patient to decide on his or her analgesic demand. It is important to control the pain from sternotomy, because excess pain may contribute to poor respiratory effort, and thus atelectasis and infection. Once the patient is tolerating oral intake, oral analgesics (with or without narcotics) can be used.

What level bed acuity is appropriate?

Heart transplant patients remain sedated and intubated immediately following surgery with continuous invasive monitors remaining in place. The most appropriate postoperative monitoring therefore takes place in an intensive care unit, preferably a unit specialized in cardiac surgical patients.

What are common postoperative complications, and ways to prevent and treat them?

The newly transplanted patient can face multiple challenges in the immediate postoperative period. Similar to coming off of bypass in the operating room, the patient continues to be at risk for right ventricular failure or biventricular failure. While hemodynamics may have been stable just prior to leaving the operating room, the consequences of chest closure may not manifest until arrival in the intensive care unit.

Pulmonary vasodilators should be continued and inotropic support should be augmented to maintain an adequate cardiac output. An already sub-optimal right ventricle may also not tolerate significant volume if blood products are being given for another potential complication, postoperative bleeding. These patients are often coagulopathic, and they should be treated early with blood products as needed to reverse any coagulation abnormalities, and they should be warmed to achieve normothermia. Continuous bleeding without signs of decreasing chest tube output warrants a re-exploration of the mediastinum.

For those with already diminished pulmonary function, weaning from the ventilator may be prolonged. Occasionally, patients develop ventilator-dependent respiratory failure and require tracheostomy. Infection is another complication that can be devastating to the heart transplant recipient. Now on an immunosuppressant regimen, they are at increased risk of infection, and thus postoperative antibiotics should be continued. Sterile technique should be used for all further procedures and access lines should be changed regularly. In some instances, a satisfactory native rhythm does not develop, and few patients require permanent pacemaker implantation.

Other complications include organ failure in cases of poor perfusion due to poor cardiac function. Renal failure is not uncommon if patients remain on multiple pressors for blood pressure support. Coagulopathy may worsen with hepatic dysfunction. Continued malperfusion of the gut may lead to distended abdomen with a lactic acidosis.

Long term concerns and complications in the heart transplant recipient include continued opportunities for infection, the development of rejection, and the occurrence of graft coronary artery disease.

What's the Evidence?

Costanzo, MR, Augustine, S, Bourge, R. "Selection and treatment of candidates for heart transplantation". Circulation . vol. 92. 1995. pp. 3593-612.

Kohl, BA, Savino, JS, Longnecker, DE, Newman, MF, Zapol, WM. "Anesthesia for heart transplantation". Anesthesiology. McGraw-Hill. 2008. pp. 1378-95.

Ramakrishna, H, Jaroszewski, DE, Arabia, FA. "Adult cardiac transplantation: a review of perioperative management (Part 1)". Ann Card Anaesth . vol. 12. 2009. pp. 71-8.

Shanewise, J. "Cardiac transplantation". Anesthesiol Clin N Am . vol. 22. 2004. pp. 753-65.

Thomas, Z, Rother, AL, Collard, CD, Hensley, FA, Martin, DE, Gravlee, GP. "Anesthetic management of cardiac transplantation. A Practical Approach to Cardiac Anesthesia". Lippincott Williams and Wilkins. 2008. pp. 439-63.

Chaney, MA. "Thoracic epidural anesthesia in cardiac surgery- the current standing". Ann Card Anaesth . vol. 12. 2009. pp. 1-3.

Keegan, MT, Brown, DR. "Perioperative antibiotics and practice: little things that make a big difference". Anesthesiol Clin N Am . vol. 22. 2004. pp. 473-91.

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