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reviewed. A 12-lead electrocardiogram prior to LT is appropriate in candidates with a history of CAD and is
supported by current The American College of Cardiology/American Heart Association recommendations
[2].
Urgent cardiology consultation is necessary whenever there is a concern regarding the status of candidates
with known CAD. Patients found to have new signs or symptoms of myocardial ischemia may be deemed at too
high of a risk to proceed with LT. Given the logistics involved in arranging for noninvasive ischemia testing,
urgent angiography prior to transplant may be indicated in selective cases. The need for urgent ischemia testing
or angiography should be addressed by the cardiologist and discussed with the entire transplant team. The deci-
sion to undergo a new ischemia evaluation may impact the immediate candidacy of the patient. In general, dis-
covery of obstructive coronary artery lesions requires further therapy as determined by current revascularization
guidelines and an appropriate delay in listing for LT
[3]. In the event of percutaneous coronary interventions
(PCI) with bare-metal stenting, a minimum of 4 weeks of dual antiplatelet therapy is required prior to relisting
for LT
[2]. Challenging clinical scenarios may occur in patients with a recent history of revascul arization or in
those on antiplatelet therapy. Clinical dilemmas may occur in patients who develop severe ESLD decompensa-
tion immediately after revascularization. Combined coronary artery bypass graft (CABG)/LT may be considered
in select candidates with multivessel disease or CAD not amenable to PCI, although there is limited evidence to
support this approach
[4]. In all LT candidates with obstructive CAD, treatment and LT planning should be indi-
vidualized and involve a multidisciplinary assessment of the risks and benefits of proceeding to LT.
Cardiac valvular disease may impact adult candidates, particularly those who are old. Prior to listing, all adult
candidates should undergo resting echocardiography
[1,5]. In the event of the diagnosis of moderate-to-severe val-
vular disease, therapy and long-term surveillance should be managed by a dedicated cardiology consultant
[1].
Aortic stenosis (AS) is the most common obstructive valvular lesion in adult patients. The presence of advanced
aortic stenosis may significantly impact the perioperative course of a LT recipient. The preoperative diagnosis and
management for severe AS in prospective LT candidates have been described previously (see
Chapter 10).
Candidates with moderate AS require close cardiology surveillance during the pretransplant waiting period as AS
can progress during the interim. Upon hospitalization or upon organ offer, repeat echocardiography may be indi-
cated. In addition, ESLD decompensation may render a patient with moderate AS hemodynamically unstable and
at an unacceptable risk to undergo LT. In these clinical settings, the role of transcatheter aortic valve replacement
(TAVR) as a bridge to transplant may be explored. For patients with severe AS, pretransplant TAVR and valvulo-
plasty or aortic valve replacement may be indicated. Combined aortic valve replacement/LT may be undertaken in
selective patients, although clinical experience is limited. (see “Postoperative pulmonary considerations” Section)
Pretransplant echocardiography may also detect severe regurgitant valvular lesions. In LT candidates, moderate-
to-severe tricuspid valve regurgitation (TR) has been shown to adversely impact post-LT outcomes, likely due to
venous congestion of the new allograft
[6]. In candidates with a history of moderate-to-severe tricuspid regurgita-
tion repeat echocardiography upon hospitalization may be warranted and cardiology reassessment is reasonable.
Echocardiographic assessment of TR severity and right ventricular size and function is crucial. Progression of tri-
cuspid regurgitation and/or impairment of right ventricular function may impact a patient’s candidacy.
Candidates with a history of cardiomyopathy (CM) should be followed by a dedicated cardiology consultant as
per current recommendations
[1]. In general, patients with severe dilated CM with a left ventricular (LV) ejection frac-
tion (EF) of less than 40% are not considered as viable candidates. Some institutions may consider listing these
patients for combined orthotopic heart transplant/orthotopic liver transplant (OHT/OLT). Candidates with less
severe forms of LV CM should be considered for LT on an individual basis. The prolonged hemodynamic and meta-
bolic stress that occurs during the perioperative period may adversely impact cardiac function in patients with under-
lying CM. Critically ill candidates with an underlying CM may be considered at a prohibitively high risk for LT,
particularly those that are hemodynamically unstable requiring vasoactive or inotropic support. Upon admission or
organ offer, any changes in clinical signs or symptoms of heart failure should necessitate urgent cardiology evalua-
tion. Resting echocardiography may provide vital information regarding a change in LV function in these patients. In
certain clinical scenarios, dobutamine stress echocardiography (DSE) may be considered to assess for augmentation of
contractility in patients with underlying CM. Regardless of DSE results, it is important to note that DSE testing does
not adequately predict a patient’s response to the prolonged stress of LT. Finally, occult LV failure should also be con-
sidered in any LT candidates with new symptoms of volume overload or hemodynamic instability. A high index of
suspicion for alcoholic CM should be maintained in patients with cardiac symptoms and a history of alcoholic cirrho-
sis. Alcoholic CM is one of the most common acquired dilated CM etiologies in many populations
[7].
Hypertrophic cardiomyopathy (HCM), a genetically transmitted CM with variable phenotypic presentation,
may adversely impa ct the perioperative course of LT candidates secondary to the development of dynamic LV
outflow tract obstruction (LVOTO)(see
Chapter 10) [8]. Patients with HCM are at risk for severe hemodynamic
294 18. Cardiopulmonary considerations for the anesthetic management of liver transplantation
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instability and sudden cardiac death in the setting of hypotension, hypovolemia, and tachycardia. Screening
echocardiography provides an accurate diagnosis of HCM by defining the characteristic anatomy as well as
detecting an LVOT gradient. The severity of LVOTO may be investigated using stress echocardiography as well.
Candidates with a history of LVOTO require evaluation by a cardiologist; surgical and interventional treatments
may be indicated prior to listing including septal alcohol ablation.
Cirrhotic cardiomyopathy (CCM), a clinical syndrome represented by cardiovascular dysfunction secondary to
underlying liver failure, has been well described (see
Chapter 10). Recent recommendations for the diagnosis and
management of CCM in LT candidates have been published
[9]. CCM may impact a majority of patients with
advanced liver disease, however, the impact of CCM on perioperative outcomes in LT patients is not well under-
stood. Routine preoperative cardiac assessment using electrocardiography, echocardiography, and cardiac and
inflammatory biomarkers may identify the clinical criteria of CCM, however, the predictive utility of these tests
is not well studied. In patients with underlying cardiac lesions, the impact of CCM may have significant implica-
tions on the perioperative risk for LT, although prospective studies are lacking in these populations. Particularly
in high- model for end-stage liver Disease (MELD) and critically ill patients, the superimposition of severe CCM
may render candidates with preexisting cardiac disease at prohibitively high risk for LT. Despite the hyperdy-
namic ventricular function typically observed in patients with ESLD, some patients with advanced CCM may
develop LV dysfunction during episodes of stress including during LT. Identification of patients at risk for LV
dysfunction is challenging. In critically ill candidates with hemodynamic instability and in candidates with
underlying cardiac lesions, a high index of suspicion should be maintained for the onset of stress-induced LV
dysfunction. Urgent echocardiography and cardiology consultation are necessary for these patients.
Current recommendations for the initial cardiac evaluation of adult LT candidates also include assessment of
right ventricular systolic pressure (RVSP) using resting echocardiography
[1]. Echocardiographic detection of an
elevated RVSP suggests underlying pulmonary hypertension. Right heart catheterization (RHC) is necessary to
establish the diagnosis of portopulmonary hypertension (POPH), a form of pulmonary hypertension secondary
to increased pulmonary vascular resistance (PVR) in patients with underlying portal hypertension (see
Chapter 10). Long-term pulmonary vasodilator therapy is recommended under the care of a pulmonary hyper-
tension consultant in patients with moderate to severe POPH
[10].
Based on studies that demonstrated adverse outcomes in LT recipients wi th mean pulmonary artery pressures
(MPAP) greater than 35 mm Hg, current guidelines suggest that the goal of pulmonary vasodilator therapy is to
lower MPAP below this threshold prior to LT
[11,12]. In patients with a known history of POPH that present for
LT, current pulmonary vasodilator therapy and recent echocardiographic or RHC studies should be revi ewed. In
candidates that have been admitted to a transplant center with decompensated ESLD, particularly in those that
are critically ill requiring intensive care, repeat echocardiography and/or RHC may be necessary. Underlying
POPH may be exacerbated by volume overload, hypoxemia, hypercarbia, acidosis, and vasopressor therapy.
Maintenance of euvolemia is important in LT candidates with underlying POPH, aggressive diuresis or renal
replacement therapy may be required to maintain euvolemia in critically ill candidates or in those with hepatore-
nal syndrome (HRS). LT candidacy may be impacted by episodic increases in pulmonary hypertension due to
ESLD decompensati on in patients with POPH. Continued consultation with a pulmonary hypertension expert is
crucial to the management of these high-risk candidates and pulmonary vasodilator therapy should be main-
tained and titrated accordingly. In POPH patients with borderline MPAP, echocardiographic demonstration of
preserved right ventricular (RV) contractility may provide important prognostic information. Conversely, RV
dilation and decreased RV contractility may suggest a prohibitive risk for proceeding with LT. As in all high-risk
candidates, determination of candidacy must be individualized using a multidisciplinary approach.
Cardiac dysrhythmias may impact LT candidates during the perioperative period. LT candidates are at risk
for both bradyarrhythmias and tachyarrhythmias. Older candidates are at risk for atrial fibrillation (AF), the most
common arrhythmia in adults. AF prevalence increases with age and is associated with increased morbidity and
mortality
[13]. Patients with a history of chronic AF require long-term cardiology management that may include
heart rate control, anticoagulation, and antiarrhythmic therapy. Acute onset of AF in the critically ill LT candi-
date may occur secondary to many factors including sympathetic activation, vasoactive medications, and volume
overload. AF with rapid ventricular rates may result in hemodynamic instability that may impact patient’s candi-
dacy. New-onset AF requires prompt cardiology evaluation and treatment. Other forms of tachyarrhythmias
including supraventricular and ventricular tachycardia may occur in LT candidates.
The underlying state of cirrhosis prolongs the QT interval, potentially contributing to a risk of ventricular arrhyth-
mias although this has not been firmly demonstrated in cirrhosis (Bernardi et al., 2012). Nevertheless, it would be pru-
dent to avoid medications that prolong the QT interval in LT candidates. Bradyarrhythmias may also impact LT
295Perioperative cardiovascular management in the liver transplant patient
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candidates. Patients with advanced liver disease may develop bradycardia secondary to chronic beta-blockade and
chronotropic dysfunction. Patients with significant bradyarrhythmias require cardiology evaluation. In patients with a
permanent pacemaker, an electrophysiology evaluation should be obtained immediately prior to LT; pacemaker inter-
rogation should determine the underlying rhythm and whether the patient is pacemaker dependent.
For LT candidates deemed to be at an especially high perioperative risk due to an underlying cardiac condition,
it is reasonable to undertake a multidisciplinary preoperative meeting to discuss perioperative planning.
Participants should include the LT anesthesia team, liver surgery team, and transplant coordinators. Cardiology,
pulmonary hypertension, cardiac surgery, cardiac anesthesia, and electrophysiology consultants may be included.
Concerns specific to each patient should be discussed and appropriate contingency planning should be made prior
to the time of transplant. Selection of a good quality donor organ is necessary; high-risk donors may not be
suitable in this patient population. A comprehensive cardiac evaluation of the patient in the operating room should
be performed prior to incision and plans for the inclusion of consultants during this initial evaluation should be
arranged accordingly. Decisions to proceed with surgery may be contingent on this evaluation. Clinical thresholds
for continuing with surgery versus aborting should be discussed with all team members in advance of surgery. In
the event of the need to abort the case due to cardiac instability, a suitable backup candidate may be identified. See
Fig. 18.1: example of pretransplant cardiac evaluation paradigm.
Intraoperative management
The operative events during LT are associated with a significant potential for hemodynamic and metabolic instability.
LT is a highly invasive procedure associated with prolonged operative stress. Most LT patients have advanced ESLD;
the typical multiorgan manifestations of this process may be enhanced during the operative period. Rapid blood loss,
massive transfusion, and complex coagulopathies frequently impact the course of LT. The prolonged intraoperative
stress of LT may impact the cardiovascular system and contribute to postoperative adverse cardiac events (see
“Postoperative pulmonary considerations” section). The superimposition of underlying cardiac conditions may further
impact the perioperative course of LT and contribute to deleterious outcomes. Unfortunately, there are no large prospec-
tive studies that have investigated the impact of intraoperative management strategies for LT candidates with underly-
ing cardiac lesions. Retrospective data mostly on the institutional level have provided insights into outcomes in some
cardiac conditions, however, the vast majority of these studies have focused on preoperative management strategies
(see “Postoperative pulmonary considerations” section). The LT anesthesiologist must navigate the intraoperative phases
of LT with close attention to important hemodynamic management strategies specific to the cardiac lesion.
Prior to surgical incision, all LT patients undergo anesthesia induction followed by a period of time, generally
3060 minutes, for vascular access procedures, placement of invasive intravascular monitors, and surgical site
preparation. Anesthesia induction should be tailored to the hemodynamic status of the patient as well as any
underlying cardiac condition. An intra-arterial catheter is placed for continuous arterial blood pressure monitor-
ing. In some patients, preinduction arterial monitoring may be considered. Some centers may place both radial
and femoral arterial catheters. Large bore central venous access is standard for all adult LT recipients.
In patients with cardiac disease, it is reasonable to utilize advanced cardiac monitoring to maximize cardiac sur-
veillance and to assess response to therapies. Pulmonary artery catheterization (PAC) allows for continuous moni-
toring of right-sided cardiac pressures, cardiac indices, and mixed venous oxygen saturation. Transesophageal
echocardiography (TEE) allows for real-time imaging of the heart and provides rapid diagnosis of major cardiovas-
cular events such as myocardial ischemia with wall motion abnormalities, LV or RV dysfunction, pericardial tam-
ponade, LVOTO, and intracardiac thrombi. Prior to incision, a comprehensive assessment of the cardiovascular
system should be made and the hemodynamic response to therapies should be assessed. Consultants such as cardi-
ologists or cardiac anesthesiologists may be included in this assessment. In the event of unanticipated cardiac insta-
bility or worsening of the underlying cardiac condition, discussions with the surgical team and consultants should
be undertaken to determine whether the case should be aborted.
There are minimal evidence to guide the clinicians regarding the perioperative management of patients with
cardiac lesions undergoing LT. For patients with the diagnosis of POPH, current guidelines support the use of
intraoperative PAC monitoring to determine cardiac index, pulmonary capillary wedge pressure (PCWP), and
PVR
[10]. TEE should be available for continuous assessment of RV size and function and ongoing pulmonary
vasodilator therapies should be continued
[10]. In general, most centers will decline LT for candidates with
POPH found to have excessively high pulmonary pressures and/or evidence of diminished cardiac output or
296 18. Cardiopulmonary considerations for the anesthetic management of liver transplantation
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Arrhythmia:
-New onset tachyarrhythmia or bradyarrhythmia: immediate cardiology consultaon
-AF with rapid ventricular rate and hemodynamic compromise: delay organ offers unl stable
-Bradycardia requiring intervenon: delay organ offers unl pacemaker placement
TTE: transthoracic echocardiography
PCI: percutaneous coronary intervenon
BMS: bare metal stent
DAPT: dual anplatelet therapy
RHC: right heart catheterizaon
LV: le ve nt ric le
RV: right ventricle
TR: tricuspid regurgitaon
AVA: aorc valve area
Portopulmonary Hypertension
Pulmonary hypertension consultaon upon hospitalizaon
Connue current pulmonary vasodilator therapies
TTE for assessment of RVSP and RV funcon
Worsened RVSP and/or RV dysfuncon Acceptable RVSP and normal RV funcon
RHC indicated Proceed to LT with PAC and TEE
Intraoperave pulmonary vasodilator therapy
RHC: MPAP< 35-40mmHg, PVR<240 dynes/s/cm-5 and preserved RV funcon
or
RHC: MPAP> 35-40 mmHg and PVR>240 dynes/s per cm-5 and/or evidence of RV dysfuncon
Hold LT offers and connue therapies per pulmonary hypertension expert
Crically ill/high-MELD candidates with POPH: maintain normovolemia with aggressive diuresis/dialysis
LT candidate with known history of CAD
-12-lead EKG
-TTE (if not performed within 6 months)
-Cardiology consult (if not performed within 6 months)
-indicaon for repeat ischemia tesng: delay LT
-determine non-invasive tesng vs. angiography
-no indicaon for repeat ischemia tesng
-non-invasive tesng
-proceed to LT
-angiography
-non-obstrucve CAD
-obstrucve CAD
-single vessel CAD: PCI with BMS and DAPT, delay LT for 4 weeks
-mulvessel CAD: consider combined LT/CABG
(-)
(+)
FIGURE 18.1 Algorithm for the man-
agement of the liver transplant patient with
known cardiac disease. Coronary Artery
Disease.
297Perioperative cardiovascular management in the liver transplant patient
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Cardiomyopathy
Immediate cardiology consultaon
Repeat TTE: assess LV funcon
Worsened LV dysfuncon Acceptable/improved LV funcon
Delay lisng Proceed to LT with PAC and TEE
Further therapies per cardiology Consider cardiology/cardiac anesthesia consultation
Serial TTEs for intraoperave management
In select candidates with LV dysfuncon: consider consultaon for combined cardiac/liver transplant
Valvular disease
Moderate-severe aorc stenosis Moderate-severe tricuspid regurgitaon
Cardiology consultaon Cardiology consultation
Repeat TTE (assess for AVA and LV funcon) Repeat TTE (assess for TR severity and RV
funcon)
Severe AS and/or LV dysfuncon Severe TR and/or RV dysfuncon
or
Moderate AS with comorbidies/high MELD
Delay LT lisng Delay LT lisng
Cardiac surgery evaluaon for pretransplant TAVR Cardiac surgery evaluaon for select candidates
Consider early TAVR evaluaon for candidates with
moderate AS and comorbidies
Arrhythmia
New onset arrhythmia Known arrhythmia
Immediate cardiology consultaon Cardiology consultaon (if none within 6 months)
SVT with RVR VT Unstable bradycardia Unstable Stable
Proceed to LT
Delay LT unl stable Rhythm device: cardiology interrogaon prior to surgery
Consider intraoperave defibrillator pads during surgery
Delay LT unl stable/defibrillator placed
Delay LT unl stable/pacemaker placed
Defibrillator/pacemaker placed or stable rhythm aer treatment
Abbreviaons:
TTE: transthoracic echocardiography PCI: percutaneous coronary intervenon
BMS: bare metal stent DAPT: dual anplatelet therapy
RHC: right heart catheterizaon LV: le ventricle
RV: right ventricle TR: tricuspid regurgitaon
AVA: aorc valve area TAVR: Transcatheter aorc valve replacement
SVT: supraventricular tachycardia VT: ventricular tachycardia
RVR: rapid ventricular response
FIGURE 18.1 (Continued)
298 18. Cardiopulmonary considerations for the anesthetic management of liver transplantation
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RV, based on data that suggests an excessive risk of adverse outcomes following LT in POPH patients with
MPAP . 35 mm Hg and PVR . 250 dynes/s per cm
25
[14].
For patients with a history of CAD, continuous TEE monitoring may be useful for the early detection of wall motion
abnormalities associated with acute myocardial ischemia. For patients with an underlying CM, cardiac index and TEE
monitoring may be crucial for intraoperative monitoring of cardiac performance. Inotropic medications may be required to
support cardiac performance; TEE and cardiac output monitoring allow for rapid assessment of inotropic therapies. TEE is
also useful for monitoring for dynamic LVOTO, particularly in patients with a history of LVOTO documented on preoper-
ative echocardiography. Routine intraoperative use of TEE during LT at United States transplant centers appears to be
increasing
[15]. However, TEE monitoring may be limited in some centers by lack of availability and limited clinical experi-
ence. For patients with permanent rhythm devices and/or implantable defibrillators, an electrophysiology consultation is
necessary prior to incision. Pacemakers should be interrogated for the presence of an underlying rhythm and optimal heart
rate and device settings should be applied. Defibrillator therapies should be deactivated for the entire surgical period and
external defibrillator pads should be placed. See
Table 18.1: Preoperative planning for LT patients with cardiac lesions.
LT surgery is usually categorized into three main phases; the preanhepatic, anhepatic, and neohepatic phases.
The preanhepatic phase begins with surgical incision and ends with comp letion of the hepatectomy. During this
period, the liver is dissected and the major he patic vessels are identified and prepared for anastomosis with the
liver graft. The preanhepatic phase may be complicated by many factors that result in significant hemodynamic
and metabolic instability. Hepatic dissection may be impacted by the presence of severe portal hypertension, dis-
torted surgical anatomy, and peritonitis. A prolonged hepatic dissection may be anticipated in patients with pre-
vious abdominal surgery or intraabdominal infection. Severe bleeding and coagulopathy may result in massive
transfusion and rapid changes in intravascular volume. Hemodynamic instability may occur due to severe vaso-
dilation that may be of a multifactorial etiology; underlying liver failure, anesthetic agents, intraabdominal sepsis,
and hypocalcemia may all contribute. Metabolic derangements including acidosis, hypothermia, and electrolyte
imbalances during this phase are common and should be anticipated. Patients with underlying cardiac conditions
may be at particular risk during the preanhepatic phase. Vasopressor support in addition to aggressive volume
resuscitation is standard during this por tion of the procedure. PAC parameters and continuous TEE may assist
the anesthesiologist in evaluating cardiac performance during this phase. In the event of severe hemodynamic
instability with evidence of cardiac failure despite maximal therapy during the preanhepatic phase, discussions
with the surgical team and consultants should be undertaken to determine whether the case should be aborted.
The anhepatic phase begins with completion of the hepatectomy and ends with reperfusion of the liver graft.
The standard approach to hepatectomy involves cross-clamping of the major vessels of the liver including the
portal vein, infrahepatic vena cava, and suprahepatic vena cava. Hepatic artery clamping usually occurs earlier
during the dissection and has a minimal impact on hemodynamics. Caval cross-clamping results in an immediate
decrease in cardiac preload. Preload supplementation and escalation of vasopressor support are common during
this phase. Reflex tachycardia should be anticipated.
The acute hemodynamic events in the anhepatic phase may be poorly tolerated in patients with underlying
cardiac disease; a period of caval test clamping may be considered prior to performing the hepatectomy to assess
the patient’s hemodynamic and cardiac responses. Additional surgical maneuvers may be considered during the
anhepatic phase in patients that may not tolerate full caval cross-clamping. Veno-venous bypass (V VB) allows for
diversion of lower caval and portal blood flow to the upper cava via the placement of temporary venous cannu-
las. One to two liters of blood flow is maintained with VVB and, allows for relief of portal and lower caval
venous congestion during the anhepatic phase. In addition, a heat exchanger is added to the VVB circuit, allow-
ing for maintenance of normothermia. A piggyback surgical technique may also be considered for patients that
may not tolerate full clamping of the cava. This surgical technique involves the anastomosis of the allograft
TABLE 18.1 Preoperative planning for LT patients with cardiac lesions.
Clearly defined planning and communication between surgery, anesthesia, coordinators, and consultant teams:
High-quality donor organ
Preoperative identification of backup candidate
Comprehensive cardiac assessment prior to incision (PAC monitoring, cardiac indices, TEE, response to therapies, cardiology/cardiac
anesthesia/cardiac surgery consultations)
Preanhepatic phase: reassessments of cardiac performance, determination of thresholds for aborting
Anhepatic phase: consider hemodynamic and metabolic support (VVB, piggyback with partial caval clamping, intraoperative dialysis)
299Perioperative cardiovascular management in the liver transplant patient
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suprahepatic cava directly to the recipient’s cava at the location of the confluence of hepatic veins. A partial caval
clamp may be employed with this technique, allowing for maintenance of partial vena cava return to the heart.
The anhepatic phase results in the loss of any residual hepatic function. Metabolic instability should be antici-
pated during this phase; progressive acidosis, hypothermia, hypocalcemia, hyperkalemia, and coagulopathy are
commonly observed. Underlying renal dysfunction due to HRS may add to the risk for further acidosis and hyper-
kalemia. Some centers employ intraoperative dialysis during LT in patients with severe HRS or in patients with
chronic renal insufficiency undergoing simultaneous liver kidney transplantation. Intraoperative dialysis may pro-
vide additional metabolic and electrolyte stability during the anhepatic phase, although there is no consensus to
recommend its use and definitive data demonstrating the outcome benefits are lacking. The anhepatic phase culmi-
nates with the release of caval claps, resulting in rapid venous return resulting in predictable increases in central
venous pressure and PAP. Instability secondary to hypothermia, hypocalcemia, and hyperkalemia is common.
Transient bradycardia and pulmonary hypertension may ensue. Some centers routinely preemptively administer
calcium chloride, anticholinergics, and vasopressors at this stage.
The neohepatic phase begins with reperfusion of the liver graft upon release of the portal vein clamp. Reperfusion
is associated with acute vasodilation secondary to the release of ischemic vasodilatory mediators from the graft, an
event described as postreperfusion syndrome (PRS). PRS may occur in up to 50% of grafts and has been associated
with a worse posttransplant prognosis in some series
[16]. Although additional therapy with vasopressors, sodium
bicarbonate, and calcium may be required to maintain stability immediately following reperfusion, most episodes of
PRS are self-limited. Following reperfusion, the hepatic arterial anastomosis is performed resulting in full revasculari-
zation of the graft. Adequate graft function can be assessed by observation of normalization of calcium levels, sponta-
neous improvement in acid-base balance, and the production of bile from the graft. Following adequate surgical
hemostasis, the biliary anastomosis is completed and the abdomen is closed. With surgical hemostasis and continued
good graft function, volume resuscitation and vasopressor support may be carefully weaned. In the event of delayed
graft function, continued metabolic and vasopressor support may be required. In cases complicated by delayed graft
function or other adverse events, the biliary anastomosis may be deferred to a later date.
The duration and complexity of surgery, the quality of the graft, and other unforeseen events may complicate the
management of LT. Patients with underlying cardiac conditions may be at risk for decompensation and may not tol-
erate extended episodes of hemodynamic and metabolic instability that may be better tolerated in patients without
cardiac pathology. The intraoperative management of LT patients with cardiac lesions must be individually tailored
to each patient. For patients with CAD or AS, maintenance of appropriate coronary perfusion pressure is critical, par-
ticularly in the presence of tachycardia. Evidence of acute ischemia during episodes of tachycardia and hypotension
requires rapid interventions to improve coronary perfusion and to prevent myocardial supply-demand imbalance.
Evidence of continued myocardial ischemia or infarction may necessitate urgent coronary angiography following sur-
gery; urgent surgical hemostasis and abdominal closure should be considered following completion of all vascular
anastomoses. For patients with underlying LV dysfunction, inotropic support may be necessary in addition to vaso-
pressors. In unique circumstances intraaortic balloon pump (IABP) or venous-arterial extracorporeal membrane oxy-
genator (ECMO) support may be considered for ventricular function; significant logistics and cardiac surgical support
are required for these interventions. In patients with POPH, continuous assessment of RV performance is crucial and
pulmonary vasodilator therapy should be maintained. Dynamic LVOTO has been reported in patients with LV septal
hypertrophy or HCM undergoing LT
[1719]. Diagnosis of systolic anterior motion of the mitral valve in conjunction
with an increase in the LVOFT systolic gradient by TEE confirms the diagnosis. LVOTO may occur particularly dur-
ing the anhepatic phase when tachycardia and hypovolemia are common. Volume resuscitation, vasopressor therapy,
and heart rate control are strategies to improve hemodynamics in patients with LVOTO.
Early postoperative cardiac evaluation and management
After LT surgery, most centers transition patients to a critical care unit for postoperative monitoring. Early graft
function is closely observed and other organ systems are assessed in the context of the functioning graft. Many cen-
ters employ intensive care specialists for the early posttransplant management of the LT patient. Early postoperative
cardiac events are common in LT patients and impact posttransplant survival. A recent single-center study docu-
mented a 20% cardiac event rate within 30 days of surgery in consecutive LT patients over a 3-years period. These
events included new onset of severe arrhythmia, acute coronary syndrome (ACS), demand myocardial ischemia,
and cardiac arrest. Age-adjusted 1-year mortality was significantly higher in patients who had a cardiac event
[20].
Similar results were also reported in another recent single-center study of 389 consecutive LT patients. Postoperative
300 18. Cardiopulmonary considerations for the anesthetic management of liver transplantation
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cardiac events within 1 month of surgery occurred in 9.8%. The majority of events were ACS, LV failure, and major
arrhythmia
[21]. A preexisting cardiac condition is likely to add to the complexity of early post-transplant manage-
ment and may contribute to a higher risk of post-transplant cardiac events. Post-transplant outcomes in LT patients
with preexisting cardiac conditions have been studied, although large prospective studies are lacking.
Significant attention has been focused on the perioperative management of CAD in LT patients and the impact of
CAD on post-LT outcomes. Older single-center studies reported variable post-LT outcomes in patients with CAD. In
one series of 32 candidates with angiographically proven CAD, 10 patients died within 3 months and the rate of intrao-
perative and early postoperative cardiac events were over 50%
[22]. However, another single-center series of 20 patients
with nonobstructive CAD (, 70% coronary lesion on preoperative angiography) reported only one early post-LT cardiac
event
[23]. CAD evaluation and management have evolved over the past 20 years. Many centers now employ a protoco-
lized pretransplant cardiac evaluation that includes aggressive angiography, revascularization of obstructive lesions, and
long-term medical management of candidates with known CAD directed by dedicated cardiology teams.
Recent studies have evaluated outcomes in larger cohorts of LT recipients with angiographically proven CAD. One
recent study evaluated the impact of obstructive CAD on early cardiac events within 1 month of surgery in 283 LT reci-
pients. CAD was found in 32%, 11% had obstructive CAD. The overall early cardiac event rate (MI, cardiac arrest,
stroke, cardiac death, heart failure, and arrhythmia) was 25%, cardiac mortality occurred in 2.1%. Analysis revealed that
underlying CAD had no impact on early cardiac events
[24]. Another recent study evaluated the impact of obstructive
CAD on 3-months postoperative cardiac events (ACS, non-ST elevation MI, heart failure, and arrhythmia) in a cohort of
87 LT patients that underwent preoperative angiography. Obstructive CAD was discovered in 29 patients; 22 of 29
underwent pretransplant revascularization. There was no difference in the rate of cardiac events between patients with
CAD (27.5%) and without CAD (25.8%). Early cardiac mortality occurred in one patient with CAD
[25]. One multicenter
investigation studied 630 LT recipients from seven United States centers. All patients underwent preoperative angiogra-
phy. Obstructive CAD (defined as 50% or greater stenosis of one or more coronary arteries) was diagnosed in 151
patients (24%). Out of 151 patients, 96 had severe ( . 70% obstruction) CAD and 80 patients underwent pretransplant
revascularization. Adjusted and unadjusted survival was not different between those with and without obstructive
CAD. Although early cardiac events were not reported, survival within 6 months was not impacted by the presence of
even severe CAD
[26]. Another single-center series analyzed rates of coronary angiography, PCI, postoperative MI, and
mortality over 10-years period in LT recipients. The authors found that aggressive angiography and revascularization of
LT candidates with obstructive CAD, reflected by increased rates of angiography and revascularization, correlated with
lower postoperative MI rates and improved unadjusted mortality
[27].
Many centers employ aggressive pretransplant surveillance for occult CAD that includes liberal coronary angi-
ography and revascularization of obstructive coronary lesions. Current guidelines do not recommend preopera-
tive revascularization for asymptomatic CAD
[2]. However, most centers are reluctant to perform LT in patients
with obstructive coronary lesions without preoperative revascularization. Furthermore, prospective studies com-
paring posttransplant outcomes between medical management and revascularization in LT candidates are limited
by logistical and ethical problems. Combined OLT/CABG is performed on selective candidates with multivessel
CAD at some institutions, although experience with this approach is limited. Overall, recent evidence suggests
that LT is appropriate in candidates with obstructive CAD that is managed by cardiology experts. Although early
outcomes appear to be favorable in LT recipients with CAD, cardiovascular events are a leading cause of long-
term posttransplant mortality; close long-term cardiac surveillance is justified in LT recipients with CAD
[28].
Patients with cardiac valvular disease may be at risk for cardiac complications secondary to the impact of pro-
longed LT surgery on the pathophysiology of the valvular lesion. There are few studies that have reported out-
comes following LT in patients with known valvular disease. One single-center review of 53 LT patients with aortic
valve disease (either aortic insufficiency of AS) found that there was no difference in survival or in early cardiac
events (ACS, CHF, and arrhythmia) between patients with aortic valve disease and a matched-control group with-
out aortic valve disease. However, patients with aortic valve disease required more posttransplant cardiac interven-
tions
[29]. Successful pretransplant aortic valve replacement followed by LT has been reported [30].However,a
prohibitively high risk of postoperative mortality has been reported in patients with cirrhosis following cardiac sur-
gery, particularly in those with MELD scores greater than 13
[31]. Recent case series have reported successful
TAVR as a bridge to LT
[3234]. One multicenter study found that there were no differences in in-hospital mortal-
ity or major cardiac events in TAVR patients with liver disease compared to a matched control cohort, although 2-
years mortality was higher in the liver disease group
[35]. TAVR appears to be a viable bridge to LT for patients
with advanced aortic valve disease that is otherwise an appropriate LT candidate.
Patients with an underlying CM may be at risk for cardiac events including worsening of v entricular function
secondary to the perioperative stresses of LT. There are no large prospective studies that have investigated
301Perioperative cardiovascular management in the liver transplant patient
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postoperative outcomes in these populations. One single-center series of 15 LT patients with HOCM reported a
33% 1-year mortality rate. All of the patients that died had preoperative resting LVOFT gradients . 60 mm Hg
documented on preoperative echocardiography, whereas those who survived had gradients near 30 mm Hg
[36].
Some patients with advanced dilated or restrictive cardiomyopathies and liver failure may undergo combined
OHT/OLT. A recent United States database series of all combined OHT/OLT performed over an 18-year period
found that the two most common indications were restrictive and dilated cardiomyopathies
[37]. Another United
States database review of combined OHT/OLT cases performed over a 13-year period reported combined graft
survival rates that matched liver graft alone and cardiac graft alone survival rates
[38].
Postoperative heart failure has been studied in LT recipients. A number of studies have reported a prevalence of
early postoperative LV heart failure from 3% to 7% in single-center consecutive series
[3942]. Recently, a single-
center study of 601 post-LT patients that underwent postoperative echocardiography within 6 months of surgery
found that the prevalence of new LV failure, defined as an EF , 40%, was 11.4%. More than half of the patients that
developed heart failure experienced recovery to an EF of 50% or greater; however, overall survival was worse in the
group with new LV failure. Although the study group did not represent a continuous LT cohort, the authors noted
that the mean MELD score of the LV failure group was 34, representing LT patients with severe liver disease. The
authors suspect that a significant proportion of those patients with heart failure developed postoperative reversible
stress-induced CM, a possible sequelae of severe underlying CCM
[43]. Takotsubo CM or transient left ventricle api-
cal ballooning syndrome is a potentially reversible form of LV dysfunction characterized by apical dilation in
response to various stressors. Although the etiology is not known, stunning of the myocardium secondary to high cat-
echolamine levels and coronary vasospasm have been suggested
[44]. Takotsubo CM has been reported during the
perioperative period of LT; the majority of cases demonstrated improvement in LV function with conservative ther-
apy
[45,46]. Perioperative heart failure in LT patients requires immediate cardiology evaluation and treatment.
Invasive therapy including LV support measures may be indicated in selective patients.
Cardiac arrhythmias may impact LT recipients during the perioperative period. Electrical instability may be more
likely in the setting of CCM, particularly during the prolonged stress of LT. There are few studies that have investigated
arrhythmias in LT population. Studies that have investigated patients with AF have demonstrated conflicting results.
One single-center series found that LT patients with preoperative AF had more postoperative adverse cardiac events but
similar survival compared to a matched control group
[47]. Another single-center series found that posttransplant sur-
vival was worse in LT candidates with preoperative AF
[48]. However, the occurrence of early postoperative AF has
been shown to be associated with a poor prognosis in LT patients. A single-center series of consecutive LT patients found
a 7.4% prevalence of early postoperative AF. Mortality and graft failure were significantly higher in patients with postop-
erative AF. In this study, the prevalence of postoperative AF was highly associated with a higher MELD score, suggest-
ing that underlying CCM may be an important factor in the development of postoperative AF in LT patients
[49].
Perioperative pulmonary management in the liver transplant recipient
Preoperative pulmonary assessment and optimization
As liver transplantation rates increase worldwide, pulmonary pathology in conjunction or independent of
chronic liver disease is an important factor in their preoperative workup. Most commonly, pulmonary assessment
is requested during the selection process due to the presence of hypoxemia or dyspnea, although it is important
that fatigue may be the only manifestation of lung disease in a patient
[50]. It should be noted that there are no
standardized recommendations for pulmonary screening in the asymp tomatic cirrhotic without concom itant lung
disease. Most centers utilize a workup consisting of chest radiography, pulmonary function testing (PFT), pulse
oximetry with arterial blood gas analysis, and echocardiography with Doppler or contrast, as these will reveal
the most common pulmonary pathologies associated with cirrhosis.
Chest radiography may demonstrate signs of fluid overload or pleural effusions, which should prompt an investi-
gation for underlying cardiopulmonary, renal, infectious, or malignant causes. However, in the absence of these con-
ditions, the most likely diagnosis is hepatic hydrothorax, which is a common complication in the pretransplant
period. This is caused by ascitic fluid in the peritoneum flowing upward through subtle diaphragmatic defects. It is a
transudative effusion, similar to effusions created by cardiac or renal disease. This can be differentiated by characteris-
tic thoracentesis findings. These include: (1) polymorphonuclear cell count of less than 500 cells/mm
3
and negative
culture, (2) total protein of concentration less than 2.5 g/dL, (3) total protein pleural fluid to serum total protein ratio
of less than 0.5, (4) lactate dehydrogenase pleural fluid to serum ratio of less than 0.6, (5) serum to pleural fluid
302 18. Cardiopulmonary considerations for the anesthetic management of liver transplantation
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albumin gradient of greater than 1.1 g/dL, (6) pleural pH of 7.4 to 7.55, (7) pleural fluid amylase concentration less
than the serum amylase concentration, and (8) pleural glucose level similar to serum level
[51].
While small to moderate effusions are usually well-tolerated, larger ones can lead to significant dyspnea, respira-
tory distress, and respiratory failure as the liver disease progresses. There is a potential infectious risk with long-
standing effusions; spontaneous bacterial pleuritis (SBPL) may develop in some patients
[52]. The cornerstone of pre-
operative management remains diuretic therapy and dietary salt restriction. Repeated thoracentesis may be under-
taken for symptomatic relief. In the setting of uncomplicated hydrothorax or SBPL, chest tube placement should be
avoided due to the risk of serious complications like empyema, hemothorax, and pneumothorax. Refractory hydro-
thorax can be managed with transjugular intrahepatic portosystemic shunt (TIPS), however, without transplantation,
mortality in this subset of patients is very high
[53]. However, long-term pulmonary outcomes have been shown to
be positive in patients with preoperative hydrothorax. One study demonstrated no difference in pulmonary and
long-term outcomes in a matched group of transplanted patients with hydrothorax versus none
[54].
Hypoxemia may be found on routine pulse oximetry in a large percentage of cirrhotics
[55]. In the setting of severe
hypoxemia with concomitant dyspnea, hepatopulmonary syndrome (HPS) must be considered (see Chapter 15 )on
hepatopulmonary syndrome and POPH. It is defined as the triad of hepatic disease (the severity of portal hypertension
does not correlate to the severity of HPS), hypoxemia, and intrapulmonary vascular dilations
[56]. Intrapulmonary vas-
cular dilations and shunting are typically diagnosed with contrast or Doppler echocardiography. Technitium-99 macro-
aggregated albumin nuclear medicine studies and ventilation/perfusion scans can also quantify the degree of shunt
fraction. The severity of HPS is graded by the degree of hypoxemia. The European Respiratory Society Task Force
grades HPS as mild (PaO
2
. 80 mm Hg), moderate (PaO
2
5 6079 mm Hg), severe (PaO
2
5 5059 mm Hg), and
very severe (PaO
2
, 50 mm Hg) [57].
In the United States, patients with severe HPS qualify for MELD exception points. It is therefore critical to rule out
any other concomitant and reversible causes of hypoxemia. In addition, these patients should also be screened for POPH,
as the diagnosis may impact prognosis. Unfortunately, the treatment of HPS is primarily supportive. Supplemental oxy-
gen therapy is utilized in severe cases to maintain adequate SpO
2
, although this has not been shown to help dyspnea or
improve quality of life. Preoperative interventions that have been reported in uncontrolled trials include somatostatin
analogs, beta blockers, and garlic
[5860]. TIPS placement and coil embolization therapy have not been consistently
shown to be successful for improvement in hypoxemia
[61,62]. There has been one case report of successful embolization
resulting improvement in oxygenation in a patient with HPS. Transplantation is curative in HPS patients. When con-
trolled for MELD score, posttransplant outcomes are similar in patients with severe HPS and in those without HPS
[63].
Abnormal PFTs have not been shown to be associated with worse short and long-term posttransplant out-
comes. However, one single-center study demonstrated that the presence of an abnormal diffusing capacity for
carbon monoxide (DLCO) and decreased total lung and residual volumes are predictors for total time on
mechanical ventilation and increased hospital length of stay
[64]. In the absence of other lung disease, typical cir-
rhotic pulmonary physiology may include an abnormal DLCO due to the effects of systemic vasodilation, hyper-
dynamic circulation, and increased plasma volume, as well as restrictive physiology due to the presence of large
volume ascites
[65]. It should be noted that the restrictive findings on PFT may be improved with ascitic drainage
prior to testing. DLCO may also be inaccurate in patients with significant hyperbilirubinemia
[66].
Obstructive findings may be demonstrated in patients with a history of smoking or chronic obstructive
pulmonary disease (COPD). In a 2008 single-center study, smoking history was common in pre-LT patients
with 27% actively smoking and 60% with a history of sm oking. In addition, 80% of patients with evidence of
airflow limitation on PFTs had no previous diagnosis of COPD
[67]. However, there are no data that demon-
strates worse posttransplant outcomes in patients with liver disease and COPD. However, based on survival
data in patients with COPD, it is prudent to consider preoperative management of their lung disease to opti-
mize their overall outcome
[68].
Certain lung abnormalities may be associated with particular liver pathologies. A directed pulmonary assess-
ment may be necessary in subsets of these patients. In primary biliary cirrhosis, patients may present with thoracic
deformities, intrapulmonary granulomas, interstitial pneumonitis, and autoimmune lung disease. Chronic active
hepatitis has been associated with interstitial pneumonitis. Primary sclerosing cholangitis has been associated with
suppurative bronchitis and intrapulmonary shunting. Alpha-1 antitrypsin deficiency can lead to the development
of panacinar emphysema with severe expiratory airflow obstruction, hyperinflation with air trapping, and bronchi-
ectasis
[66]. Hereditary hemorrhagic telangiectasia uncommonly presents with pulmonary arteriovenous malforma-
tions with resulting hypoxemia that can be effectively treated with coil embolization
[69].
As liver disease progresses in severity, superimposed pulmonary conditions may present including aspiration
secondary to encephalopathy, pneumonia secondary to cirrhosis mediated immune dysfunction, fluid overload,
303Perioperative pulmonary management in the liver transplant recipient
III. Cardiovascular system in liver failure
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