Intraoperative Intracardiac Thrombus in Liver Transplant: A 9-year Retrospective Review Focusing on Treatment and Outcomes
“This study characterizes incidence and outcomes surrounding intracardiac thrombosis (ICT) during liver transplantation over 9 years at a single center before and after the routine use of transesophageal echocardiography (TEE). Adult liver transplantation patients from 2011 to 2020 were divided into eras based on routine TEE use. ICTs were identified by querying anesthetic records for search terms. Descriptive statistics included counts and proportions for baseline recipient, donor, intraoperative, and postoperative characteristics. Outcome data were based on date of hospital discharge and date of death. The incidence of ICT increased in the TEE era (2016-2020) compared with the pre-TEE era (2011-2015; 3.7% [25/685] vs. 1.9% [9/491]; p < 0.001). Patients with ICT had significantly higher Model for End-Stage Liver Disease-sodium (MELD-Na) scores, pretransplant hospitalization, malignancy, drug-induced liver injury, hypertension, deep vein thrombosis, reperfusion syndrome, transfused platelets and cryoprecipitate, and use of hemostatic medications. A higher proportion of patients in the ICT group underwent simultaneous liver-kidney transplantation. The patients with ICT were similar, except patients in the pre-TEE era had higher MELD-Na scores and incidences of hepatitis C virus and lower incidences of encephalopathy. In the pre-TEE era, all ICTs presented as intraoperative cardiac arrest, and the 30-day mortality in the setting of ICT was 66.7% (6/9). During the TEE era, 80% of ICTs were diagnosed incidentally or attributed to hemodynamic instability (p = 0.002). The 30-day mortality rate was 36% (9/25) in the TEE era (p = 0.25). ICT incidence increased in the TEE era, yet the mortality rate was lower, suggesting that routine intraoperative TEE may lead to the early detection of ICT prior to hemodynamic collapse.”
Comments made by Cara Crouch, MD
Intracardiac thrombus (ICT) is a rare but devastating complication during orthotopic liver transplantation (OLT). This study evaluates the incidence of ICT before and after TEE use during OLT became standard at a single institution. As expected, there was a higher incidence of ICT found once TEE use became standard practice, however, an important point to note from this article is the lower mortality rate during the TEE era (36% vs 66.7% in the pre-TEE era). The authors point out that earlier detection of thrombi via TEE may allow for more prompt treatment prior to the progression to full cardiovascular collapse.
This article also provides a thorough review of a single institutions experience with ICT over a 9-year period and the authors provide extensive baseline characteristics of the patients who developed this complication. The authors found that patients undergoing simultaneous liver-kidney transplant (SLK) seemed to have a higher incidence of ICT, though the use of intraoperative renal replacement therapy (non-heparinized circuit) was higher in patients undergoing SLK and the authors question if this may be the reason. Patients who experienced ICT were more likely to have post-reperfusion syndrome, platelet and cryoprecipitate transfusion, as well as administration of recombinant factor VII, tranexamic acid and desmopressin. This article offers good support for the standardization of intraoperative TEE use in patients undergoing liver transplantation. However, it is understood that this may not be feasible at some institutions, the authors also highlight several intraoperative factors that appear to be correlated with the development in ICT. This information may prove useful in helping to determine which patients may benefit from TEE probe placement given that they are higher risk for this potentially fatal complication.
- Fagelman E, Wang R, Tomlinson A, Romano D, Schlichting N, Zerillo J, DeMaria S, Smith N. Intraoperative Intracardiac Thrombus in Liver Transplant: A 9-year Retrospective Review Focusing on Treatment and Outcomes. Liver Transplantation. April 2022.
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T. Everett Jones, MD, and Yong G. Peng, MD, PhD, FASE, FASA
Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL
The learning objectives of this PBLD are to:
1) Define the essential evaluation of patient comorbidities before left ventricular assist device (LVAD) placement.
2) Review the impact/implications of a previous MitraClip procedure for patients undergoing LVAD placement.
3) Identify the pertinent transesophageal echocardiography (TEE) findings relevant to LVAD placement.
4) Discuss the strategic approach and management of patients undergoing LVAD placement.
A 49-year-old man had a past medical history of ischemic cardiomyopathy, coronary artery bypass grafting 10 years prior, chronic renal insufficiency, obesity (BMI 36), congestive heart failure, left ventricular ejection fraction (LVEF) of 20% to 25%, previous St. Jude pacer/automatic implantable cardioverter defibrillator (AICD) for primary prevention, and severe mitral regurgitation after a MitraClip procedure (Abbott, Abbott Park, IL, USA). He presented for placement of a HeartMate III left ventricular assist device (LVAD) as destination therapy. A pre-induction radial arterial line was placed. General endotracheal anesthesia was induced with midazolam, fentanyl, lidocaine, propofol, and rocuronium. The right internal jugular vein was then cannulated using ultrasound guidance with an introducer and a pulmonary artery catheter was floated without incident. His AICD was turned off before the procedure began. Transesophageal echocardiography (TEE) revealed a dilated left ventricle (LV) with global severe hypokinesis and a LVEF of approximately 20%, along with grossly normal right ventricular (RV) function, severe mitral regurgitation, and mild tricuspid regurgitation. A MitraClip was visualized without evidence of mitral stenosis (mean gradient 2 mmHg; Figure 1A and B). A possible residual atrial septal defect (ASD) was identified by color-flow Doppler examination of the interatrial septum. The patient underwent redo sternotomy and was cannulated for cardiopulmonary bypass (CPB). While on CPB, an iatrogenic ASD resulting from his previous MitraClip procedure was closed, the Heartmate III LVAD inflow cannula was placed in the apex of the LV, and the outflow cannula was placed in the ascending aorta. While examining the patient with TEE while he was on CPB, we noted that the inflow cannula was not optimally aligned (Figure 2). The surgeon adjusted the inflow cannula to allow for a more appropriate flow. The LVAD speed was slowly increased in increments of 200 RPMs while the patient was weaned from CPB. A pump speed of approximately 5100 RPMs was eventually reached. The patient was successfully weaned from CPB and protamine was administered. The total CPB time was 147 min. The patient was successfully transitioned to LVAD support without difficulty on infusions of milrinone, epinephrine, norepinephrine, and 40 ppm inhalational nitric oxide (NO). Inflow cannula peak velocities measured between 80 and 100 cm/s on TEE. The patient was transported to the cardiac intensive care unit uneventfully. He was extubated on postoperative day 2.
1. Why is preoperative evaluation of patient comorbidities important for LVAD placement?
Preoperative evaluation is vital for ventricular assist device placement. Discussions with the surgeon about the urgency of placement (elective vs emergent), planned surgical approach (sternotomy vs thoracotomy), and likelihood of RV assist device placement, as well as any additional planned surgical procedures is necessary. It is important to determine the etiology of the patient’s cardiac and coexisting diseases, paying particular attention to the patient’s current medications, inotropic infusions, pulmonary artery pressure, and RV function. The presence or absence of an AICD and the management plan for the AICD should be noted. Additionally, take note of the hematocrit; many patients have received erythropoietin stimulating agents preoperatively and removal of autologous blood may be considered.
2. What pertinent preprocedural TEE findings are relevant for LVAD placement?
A systematic TEE examination is essential before LVAD placement, paying particular attention to the assessment of structural and functional abnormalities. Significantly reduced LV contractile function in this population increases the risk of LV thrombus. The presence of a intracardiac shunt such as a patent foramen ovale (PFO), ASD, or ventricular septal defect (VSD) can lead to hypoxia after LVAD placement secondary to right to left shunting. Structural valvular pathologies such as aortic regurgitation or mitral stenosis will negatively affect the function of the LVAD. Close to normal RV systolic function is essential for the success of LVAD placement.
3. How can a history of a MitraClip procedure affect LVAD placement?
The MitraClip procedure is a structural heart intervention that attempts to address severe mitral regurgitation in patients whose comorbidities prohibit an open mitral valve repair or replacement. The procedure requires a trans-septal puncture through the interatrial septum to deliver the mitral clip. The intervention is successful when a significant reduction of mitral regurgitation is achieved without causing mitral stenosis. However, in certain circumstances, mitral clip application may result in mitral stenosis and/or no significant reduction of mitral regurgitation. The ASD (Figure 3) is typically not closed at the conclusion of the procedure. This iatrogenic intracardiac shunt typically closes spontaneously over time, but this is not always the case. If it is present in a patient undergoing LVAD implantation, it is necessary to close the defect.
4. How can TEE guide LVAD inflow and outflow cannula placement?
The preoperative TEE examination should rule out LV thrombus, and intraoperatively it can guide the surgeon to locate an appropriate area to place the inflow cannula at the LV apex. The goal is to directly align the inflow cannula with the mitral valve inflow. The LVAD inflow cannula should avoid angulation toward either the septal wall or the lateral wall. The LVAD inflow cannula velocity should be laminar and approximately 100 cm/s. The LVAD outflow cannula is located in the proximal ascending aorta. TEE assessment should be free of aneurysm, dissection, or significant atheromatous disease at the site of LVAD outflow cannula placement.
5. Should separation from CPB be accomplished by setting the LVAD to full speed immediately?
LVAD devices require constant hemodynamic and echocardiographic monitoring in the immediate post-implantation period during and after weaning from CPB. LVAD function is preload dependent and afterload sensitive. After separation from CPB, ensuring adequate fluid replacement and making slow adjustments to the LVAD speed are strongly recommended. Failure to maintain normovolemia and adequate LV filling can lead to “suction events” (Figure 4), which can lead to acute right heart failure due to changes in the RV geometry. The medical professional should be aware of the potential for suction events and rely on institutional/peer-reviewed protocols to prevent such devastating yet avoidable events.
6. Why is monitoring RV systolic function essential during placement of a LVAD?
Many patients undergoing LVAD placement present with pulmonary arterial hypertension with tenuous RV systolic function. It is essential to constantly monitor RV systolic function during the course of LVAD placement. Particular attention should be paid to avoiding increases in pulmonary vascular resistance. Thus, it is necessary to avoid hypoxia, hypercarbia, significant sympathetic stimulation, hypothermia, and acidosis; these factors may result in an acute increase in pulmonary vascular resistance. Administration of inotropic agents such as milrinone and dobutamine, as well as pulmonary vasodilators such as inhaled nitric oxide or epoprostenol can be helpful to ensure that the RV systolic performance can provide the LV filling necessary to keep up with the increased LV output from LVAD function.
7. What is the pulsatility index?
The pulsatility index (PI) is a measure of the pulse flow through the LVAD device from native heart function. LV contraction leads to an increase in ventricular pressure that increases pump flow; the flow pulses generated are measured and averaged over 15 s. The PI increases with enhancement of LV ejection. The PI can abruptly drop due to a sudden decrease of LV output resulting from arrhythmias or LV preload. Barring a decrease in circulating volume, acute RV failure can also lead to a drop in the PI.
8. How should fluid resuscitation and vasoactive support be balanced immediately after LVAD implantation?
TEE is an invaluable modality to guide fluid management after LVAD placement. Appropriate LVAD function demands primary fluid replacement instead of continued increases in vasoactive medications. Echocardiography can not only assess the appropriate alignment of the LVAD inflow cannula at the LV apex, but can also be used to ensure adequate filling of the LV. Hypovolemia and acute RV failure both lead to inadequate LV filling that can result in “suction events.” These events can precipitate acute right heart failure or worsen preexisting right heart failure. TEE is useful to evaluate RV function after LVAD implantation, and if RV function is adequate, then volume replacement should be considered. LVAD devices are afterload sensitive and preload dependent. Therefore, vasoconstrictors should not be the primary choice to rescue hypotension; rather, consideration of volume replacement is warranted. Inotropic agents such as epinephrine, milrinone, or dobutamine should be administered to support RV systolic function to promote LV filling. This strategy will allow for appropriate performance of the LVAD device.
- Silverton NA, Patel R, Zimmerman J, et al. Intraoperative transesophageal echocardiography and right ventricular failure after left ventricular assist device implantation. J Cardiothorac Vasc Anesth. 2018;32;2096–2103.
- Gudejko MD, Gebhardt BR, Zahedi F, et al. Intraoperative hemodynamic and echocardiographic measurements associated with severe right ventricular failure after left ventricular assist device implantation. Anesth Analg. 2019;128;1:25–32.
- Baxter RD, Tecson KM, Still S, et al. Predictors and impact of right heart failure severity following left ventricular assist device implantation. J Thorac Dis. 2019;11;6:S864–S870.
- Rich JD, Burkhoff D. HVAD flow waveform morphologies: theoretical foundation and implications for clinical practice. ASAIO J. 2017;63:526–535.
- Katz WE, Conrad Smith AJ, Crock FW, Cavalcante JL. Echocardiographic evaluation and guidance for MitraClip procedure. Cardiovasc Diagn Ther. 2017;7:616–632.
Figure 1. (A) Mid-esophageal four-chamber view reveals the mitral clip between the anterior and posterior mitral valve. (B) Pulsed-wave Doppler reveals a mitral inflow pattern with a peak gradient of 7 mm Hg and mean gradient of 2 mm Hg.
Figure 2. Mid-esophageal two-chamber view reveals malalignment of the LVAD inflow cannula.
Figure 3. Modified mid-esophageal aortic short-axis view reveals classic example of residual ASD after the MitraClip procedure.
Figure 4. Mid-esophageal four-chamber view demonstrates severe hypovolemia with an obliterated left ventricle.
Michael Curtis, MD
University of California, San Francisco
Patients with end-stage heart failure that are scheduled for orthotopic heart transplantation (OHT) frequently present with cardiac implantable electronic devices (CIEDs), such as automatic implantable cardioverter-defibrillators (AICDs) and pacemakers, with or without a cardiac resynchronization therapy function (CRT). AICDs may prevent sudden cardiac death from ventricular arrhythmias that these patients are susceptible to, and pacemakers protect against bradyarrhythmias. CRT may provide both improved cardiac function and symptomatic relief. Given that these are all treating intrinsic properties to the patient’s native heart, CIEDs are typically removed during the intraoperative course of an OHT. Unfortunately, this is not always successfully accomplished – either purposefully or inadvertently – placing the patient at risk of adverse sequelae in the post-operative period.
Incidence of Retained CIED Hardware
Removing a CIED involves extracting the generator itself from its pocket, as well as the leads that most often transverse the subclavian vein to the superior vena cava (SCV) before implanting into portions of the right atrium (RA) and right ventricle (RV). CIEDs with a CRT function will also have an additional lead positioned in the coronary sinus that will need to be removed. Leads that have been in place for many years, especially for those which include defibrillation coils, may have scar tissue firmly grasping on the leads, which can make extraction a challenging process. Specialized equipment and procedures do exist for these difficult situations, but it is rarely feasible to have all of these tools and skillful operators available during urgent procedures such as an OHT.
Unfortunately, this means that lead fragments are frequently retained after OHT. In fact, multiple studies at a variety of institutions have shown that 16.2-47.5% of patients getting a CIED removed during OHT still had retained material visible on chest radiography post-operatively.(1-4) The large majority of these leads are in the subclavian vein or SVC, but rare cases of migration to RV and even the left ventricle (LV) have been reported.(5, 6) Risk factors for such retained hardware appear to be: age greater than 50 years, the presence of two or more leads, leads that have been in situ greater than 12 months, and the presence of a dual-coil defibrillator lead.(4)
Outcomes from Retained CIED Hardware
This retained CIED hardware does appear to increase the risk of upper extremity DVT, and thus in theory related cardiovascular complications like pulmonary embolism.(3, 7) These hardware fragments may also increase the patient’s future radiation exposure, given both the artifacts they may cause during imaging plus the physical obstruction they may pose when using bioptomes for cardiac biopsies in the post-operative period.(3) This may seem insignificant, but these patients are already at increased risk for malignancies than the general population, and this additional exposure may serve to further elevate that risk.(8)
Although there is theoretical concern about retained CIED fragments becoming infected and leading to bacteremia, especially in such an immunosuppressed population, thankfully studies have found that this is a relatively rare event.(3, 4, 7) There is worry that retained hardware will preclude the use of future MRI scans, or at the very least place those patients at risk of thermal injury in the MRI scanner.(7) While the number of OHT patients with lead fragments getting MRIs has been small, there do not seem to be any reported adverse events.(3, 4) Finally, it is not hard to imagine negative consequences from intracardiac migration from lead fragments, such as cerebral or pulmonary embolism, hemopericardium from ventricular perforation, or major valvular damage. However, none of these events were seen in the rare, reported incidences of this situation.(5, 6)
Looking for Retained CIED Hardware
Careful inspection of removed hardware and the surgical field during OHT is the most important and timely method to either ensure that no fragments are left behind or to raise suspicion that challenging to remove segments may have been retained. Intraoperative transesophageal echocardiography (TEE) may also be able to detect intracardiac fragments or those in the proximal SVC, though without a high index of suspicion, these fragments may not be immediately obvious (Figure 1 and Figure 2) when focused on evaluating donor heart function and anastomotic sites while coming off cardiopulmonary bypass (CPB) with tenuous hemodynamics. Even if immediately detected, it understandably might only prompt a discussion with the surgical team about weighing the relative risk of prolonging CPB time versus planning for later removal endovascularly.
However, as discussed above, the majority of these retained CIED leads remain in the SVC or subclavian veins, which cannot be seen on TEE. Thus, evaluating for their presence on post-operative chest radiography still needs to be an important modality to use during the recovery process.
Patients presenting for OHT frequently also need concurrent removal of existing CIED hardware. Due to various factors, retention of hardware fragments, especially dual-coil defibrillator leads, is relatively common and can be associated with negative sequelae such as DVTs or, more rarely, infection if not removed. Intraoperative TEE can play an important role in early identification of intracardiac or proximal SVC hardware, but has limitations in evaluating the locations where retention is most frequent. Fragments can be more extensively visualized on other post-operative imaging modalities such as chest radiography, which should be performed in an expedited manner once the patient is stable. No clear guidelines exist for the timing of removing the leads if found. However, many advocate for them to be removed as soon as possible, typically via endovascular approach, in order to eliminate the ongoing risk of complications.(2)
Figure 1 – Transgastric mid-papillary short axis view on transesophageal echocardiography (TEE) after orthotopic heart transplant (OHT) demonstrating an echodense object at the location of the anterolateral papillary muscle (circled in red above). Additional post-operative imaging clarified that this was a retained cardiac implantable electronic device (CIED) lead fragment.
Figure 2 – Concurrent mid-esophageal four chamber and two chamber views on transesophageal echocardiography (TEE) after orthotopic heart transplant (OHT) showing a linear, echodense object extending from the mitral valve to the anterior left ventricular wall (red arrows above). Additional post-operative imaging clarified that this was a retained cardiac implantable electronic device (CIED) lead fragment.
- Kim J, Hwang J, Choi JH, Choi HI, Kim MS, Jung SH, et al. Frequency and clinical impact of retained implantable cardioverter defibrillator lead materials in heart transplant recipients. PLoS One. 2017;12(5):e0176925. Epub 20170502. doi: 10.1371/journal.pone.0176925. PubMed PMID: 28464008; PubMed Central PMCID: PMC5413001.
- Kusmierski K, Przybylski A, Oreziak A, Sobieszczanska-Malek M, Kolsut P, Rozanski J. Post heart transplant extraction of the abandoned fragments of pacing and defibrillation leads: proposed management algorithm. Kardiol Pol. 2013;71(2):159-63. doi: 10.5603/KP.2013.0009. PubMed PMID: 23575709.
- Alvarez PA, Sperry BW, Perez AL, Varian K, Raymond T, Tong M, et al. Burden and consequences of retained cardiovascular implantable electronic device lead fragments after heart transplantation. Am J Transplant. 2018;18(12):3021-8. Epub 20180424. doi: 10.1111/ajt.14755. PubMed PMID: 29607624.
- Martin A, Voss J, Shannon D, Ruygrok P, Lever N. Frequency and sequelae of retained implanted cardiac device material post heart transplantation. Pacing Clin Electrophysiol. 2014;37(2):242-8. Epub 20140115. doi: 10.1111/pace.12274. PubMed PMID: 24428516.
Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study
“Background: Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function.
Methods: The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex.
Results: The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively.
Conclusions: High percent normal saline administration is associated with delayed graft function in kidney transplant recipients.”
Comments by Scott Byram M.D.
This article1 from Anesthesiology was chosen because of the extremely common and often contentious debate on choice of crystalloid during renal transplantation. Many anesthesiologists prefer to avoid lactated ringers or PlasmaLyte (Baxter International Inc., USA) in favor of normal saline, because of the perceived risk of perioperative hyperkalemia after high volume resuscitation with potassium-containing crystalloids. Conversely, several studies have actually shown MORE hyperkalemia with normal saline administration due to hyperchloremic acidosis and subsequent extracellular potassium shift.
This study was a retrospective database review of 2515 patients who received a renal transplant from 2005-2015 at a single institution. The authors grouped patients into 3 groups based on percent of fluid resuscitation consisting of normal saline (low ≤30%, intermediate 30-80%, and high ≥80%). The primary outcome variable was delayed graft function as defined by need for hemodialysis within 1 week of transplantation. The results of this study showed the incidence of delayed graft function was 15.8%, 17.5%, and 21% respectively in the low, intermediate, and high saline groups. This association was still seen regardless of donor type (deceased vs. living); however, the magnitude was much greater in deceased donors. The authors speculated that the delayed graft function in the high saline group was due to a high chloride load causing decreased renal perfusion and glomerular filtration rate, which has been previously demonstrated in animal and volunteer studies. In this retrospective cohort study, a high percentage of normal saline administration was associated with delayed graft function in renal transplant recipients.
Kolodzie K, Cakmakkaya OS, Boparai ES, Tavakol M, Feiner JR, Kim MO, Newman TB, Niemann CU. Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study. Anesthesiology. 2021 Oct 1;135(4):621-632. doi: 10.1097/ALN.0000000000003887. Erratum in: Anesthesiology. 2022 Jan 1;136(1):251. PMID: 34265037.