SATA

Society for the Advancement of Transplant Anesthesia

Article of the Month

December 2022 Article of the Month

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Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

Abstract:

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients.

METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded.

RESULTS: Two hundred and ninety-seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8+/-8.8 vs. 25+/-8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU.

CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Comments made by Cale Kassel M.D., FASA

 

Summary:

In this retrospective study, the Johnson-Laghi et al reviewed patients undergoing liver transplantation focusing on patients with known alcoholic liver disease and previous opioid use prior to transplantation. As has been described, the use of pre-operative opioids is associated with worse outcomes in other surgical procedures. The authors sought to identify if post-LT opioid use (p-LTOU) was greater in patients with alcoholic liver disease (ALD) compared to those without alcoholic liver disease.

Patient demographic data included diagnosis of psychiatric disease, use of psychiatric medications, use of illicit drugs, use of benzodiazepines, use of marijuana, prior alcoholic rehabilitation, and legal encounters related to alcohol (DUI). Use of pre-operative opioids included use both scheduled and as needed within the three months prior to transplantation. The total dose was converted to morphine equivalents for comparison.

Overall, opioid use post-LT was more common with patients with ALD compared to those without at 30, 60, and 90 days. At 90 days, 44% of ALD patients were taking opioids compared to 27% of non-ALD patients (p = 0.004). Multi-variate logistic regression demonstrated pre-LT opioid use, primary diagnosis of ALD, and lower MELD predicted 90-day post-LT opioid use.

Further analysis showed specific risk factors for p-LTOU at 60 days to include living alone. As the authors noted, this shows the importance of good social support for patients evaluated for LT. This was not a significant variable at 90 days however.

As the authors noted, more research is needed on this topic to further identify risk factors for opioid use following LT. Additionally, this is an area for anesthesiologist involved in the listing process to add value. Opioid tapering prior to LT may provide benefit for patients. Identifying patients with any patient who take opioids, can allow for early intervention including opioid tapering.

October 2022 Article of the Month

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Utilization and outcomes of deceased donor SARS-CoV-2–positive organs for solid organ transplantation in the United States.

Abstract:

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.

 

Comments made by Cale Kassel M.D., FASA  

Summary:

When the COVID-19 pandemic began, there were obvious concerns among the transplant community. First and foremost, how could we protect patients following transplant and while waiting from transplant. As our understanding of COVID-19 evolved, so to did our ability to manage the disease in organ transplantation. The question of utilizing COVID-positive organs for transplantation emerged. Schold, et al reviewed SRTR data to look at utilization of COVID-positive organs (kidney, liver, and heart) from early in the pandemic to present. Several key findings emerged as they evaluated the data. 

First, they found utilizing COVID-positive grafts did not demonstrate worse outcomes for patients. Graft survival was similar between COVID-positive and COVID-negative grafts for kidney (95.5% vs. 95.3%), liver (93.9% vs. 97.0%), and heart (92.8% vs. 96.7%). 

Second, utilization of COVID-positive donors remained low. Recovery of COVID-positive organs was lower for kidneys, livers, and hearts. Additionally, discard of recovered grafts were lower in COVID-positive grafts. However, kidney graft discard rate of COVID-positive grafts was lower in the later study period (Dec 2020-April 2021) compared to the early study period (March 2020-November 2020). The overall rate of discard for COVID-positive kidneys was still lower than COVID-negative. Heart and liver discard rates were lower in COVID-positive donors as well. 

As we continue to learn more about the effect of transplantation of COVID-positive organs, we can continue to optimize patients and grafts to improve outcomes. Early data from this study and others suggests COVID-positive grafts can provide a safe option for patients awaiting transplantation.

References:

Schold JD, Koval CE, Wee A, Eltemamy M, Poggio ED. Utilization and outcomes of deceased donor SARS-CoV-2–positive organs for solid organ transplantation in the United States. American Journal of Transplantation 2022;22(9):2217-2227. DOI: https://doi.org/10.1111/ajt.17126.

September 2022 – Article of the Month

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Factors Associated With Postreperfusion Syndrome in Living Donor Liver Transplantation: A Retrospective Study

Abstract

Background: Postreperfusion syndrome (PRS) after portal vein reperfusion during liver transplantation (LT) has been reported to cause rapid hemodynamic changes and is associated with a prolonged postoperative hospital stay, renal failure, and increased mortality. Although there are some reports on risk factors for PRS in brain-dead donor LT, there are a few reports on those in living donor LT. Therefore, we retrospectively reviewed the factors associated with PRS to contribute to the anesthetic management so as to reduce PRS during living donor LT.

Methods: After approval by the ethics committee of our institution, 250 patients aged ≥20 years who underwent living donor LT at our institution between January 2013 and September 2018 were included in the study. A decrease in mean arterial pressure of ≥30% within 5 minutes after portal vein reperfusion was defined as PRS, and estimates and odds ratio (OR) for PRS were calculated using logistic regression. The backward method was used for variable selection in the multivariable analysis.

Results: Serum calcium ion concentration before reperfusion (per 0.1 mmol/L increase; OR, 0.74; 95% confidence interval (CI), 0.60-0.95; P < .001), preoperative echocardiographic left ventricular end-diastolic diameter (per 1-mm increase: OR, 0.90; 95% CI, 0.85-0.95; P < .001, men [versus women: OR, 2.45; 95% CI, 1.26-4.75; P = .008]), mean pulmonary artery pressure before reperfusion (restricted cubic spline, P = .003), anhepatic period (restricted cubic spline, P = .02), and graft volume to standard liver volume ratio (restricted cubic spline, P = .03) were significantly associated with PRS.

Conclusions: In living donor LT, male sex and presence of small left ventricular end-diastolic diameter, large graft volume, and long anhepatic period are associated with PRS, and a high calcium ion concentration and low pulmonary artery pressure before reperfusion are negatively associated with PRS.

Comments by Scott Byram M.D.

Summary:

Hemodynamic management is often difficult and complex during orthotopic liver transplantation (OLT).  One stage that can be particularly challenging to the anesthesiologist is the initiation of the neohepatic stage signaled by reperfusion of the liver graft.  Post reperfusion syndrome (PRS) is known to cause rapid hemodynamic changes and is seen within minutes of opening the portal vein.  The exact mechanism of PRS is still not understood, but is most likely multifactorial.  PRS has been associated with several poor postoperative outcomes including renal failure, increased length of stay, and increased mortality. 

                In this retrospective study, the authors sought to identify risk factors for developing PRS after  living donor (LD) OLT.  Most prior studies on this topic have examined PRS with brain death donors.  For this study, PRS was defined as a decrease in mean arterial pressure by more than 30% within 5 minutes of reperfusion that persisted for longer than 1 minute.  250 charts of LD OLT recipients were reviewed.  Of these patients, 73 (29%) met the criteria for PRS. There were no significant baseline differences in sex, age, liver function, general condition, comorbidities, blood pressure, or medication between the two groups (PRS vs. non-PRS).  Through multi-variable statistical analysis, the authors identified five significant risk factors for developing PRS.  Characteristics associated with increased risk for PRS were: male sex, low left ventricular end-diastolic diameter on pre-op TTE, prolonged anhepatic duration, large graft volume, low ionized calcium just prior to reperfusion, and high mean pulmonary artery pressure (mPAP) just prior to reperfusion.    These last two risk factors are particularly interesting because the anesthesiologist is able to modify both calcium concentration and mPAP prior to reperfusion, therefore potentially decreasing the risk for PRS.

                The authors went on to speculate as to why these risk factors play a role in the development of PRS.  However, they strongly cautioned readers not to assume that these associations were causative given the retrospective nature of this study.  The ultimate conclusion of this paper was that these five factors could aid in predicting the probability of PRS, but randomized control trials would be needed to establish preventative strategies.

References

  1. Umehara K, Karashima Y, Yoshizumi T, Yamaura K. Factors Associated With Postreperfusion Syndrome in Living Donor Liver Transplantation: A Retrospective Study. Anesth Analg. 2022 Aug 1;135(2):354-361. doi: 10.1213/ANE.0000000000006002. Epub 2022 Jul 5. PMID: 35343925.

 

Article of the Month July 2022

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Hyponatremia and Liver Transplantation: A Narrative Review.

Abstract:

Hyponatremia is a common electrolyte disorder in patients with end-stage liver disease (ESLD) and is associated with increased mortality on the liver transplantation (LT) waiting list. The impact of hyponatremia on outcomes after LT is unclear. Ninety-day and one-year mortality may be increased, but the data are conflicting. Hyponatremic patients have an increased rate of complications and longer hospital stays after transplant. Although rare, osmotic demyelination syndrome (ODS) is a feared complication after LT in the hyponatremic patient. The condition may occur when the serum sodium (sNa) concentration increases excessively during or after LT. This increase in sNa concentration correlates with the degree of preoperative hyponatremia, the amount of intraoperative blood loss, and the volume of intravenous fluid administration. The risk of developing ODS after LT can be mitigated by avoiding large perioperative increases in sNa concentration. This can be achieved through measures such as carefully increasing the sNa pretransplant, and by limiting the intravenous intra- and postoperative amounts of sodium infused. SNa concentrations should be monitored regularly throughout the entire perioperative period.

Comments made by Cale Kassel M.D., FASA  

Summary:

Anesthesiologists encounter hyponatremia in LT patients frequently. This review outlines the multiple factors that contribute to the development and management of hyponatremia.[1] While the risk of hyponatremia is well-known for patients on the waiting list, the effect on post-operative outcomes remains unclear. A few early studies on hyponatremia in LT showed increased 90-day mortality but more recent studies listed show no difference. However, some research does show increased ICU length of stay and morbidity. Of note, one study of over 40,000 patients did show increased mortality for patients with serum sodium less than 120 mmol/L indicating perhaps serve or profound hyponatremia may carry more risk.

Osmotic demyelination syndrome (ODS) is the biggest concern with rapid serum sodium correction. This potentially lethal condition can occur when serum sodium is increased more than 8 mmol/L in 24 hours. Incidence of ODS is 0.8-1.4% in LT patients compared to 0.6% in the general population and carries a higher risk of morbidity and mortality (77% for LT patients vs. 45% for non-LT patients).

Perioperative management of hyponatremia requires attention from the pre-operative evaluation through the post-operative period. While time is often limited pre-LT, there are a few options to increase serum sodium. Holding loop diuretics, free-water restriction, and high-concentration albumin (25%) can be used. Consulting with the nephrology team can be of great value as well.

Intra-operative management certainly can be challenging. Close monitoring is essential and understanding the sodium concentration of the fluids, medications, and blood products use can guide your treatment. The use of viscoelastic testing should be considered to limit the use of blood products such as plasma (with a sodium concentration of 172 mmol/L). The use of CRRT can typically uses a dialysate solution with 140 mmol/L of sodium so in patients with hyponatremia, discussion with the nephrologists is needed to explore ways to decrease sodium concentration. The authors cite a suggestion that adds sterile water (in predefined amounts) to create hyponatremic dialysate solutions.

Many solutions and blood products we administer contain significant sodium concentrations. The authors provide a great table with the recommended amount of D5W you can add to reduce the sodium concentration to 125 mmol/L. For example, a liter of normal saline would require the addition of 232 mL of D5W. In lieu of fresh frozen plasma or cryoprecipitate, the use of factor concentrates can help improve the coagulation profile without significant increases in sodium concentration.

Post-operatively, continued monitoring is important as the fluid shifts can continue despite the new graft. Again, limiting the increase of serum sodium to less than 4-6 mmol/L per 24 hours is important as is monitoring for signs of ODS.

Overall, this review was a great summary of the current state of knowledge while also providing several useful clinical suggestions for anesthesiologists.

References:

[1] Verbeek TA, Saner FH, Bezinover D. Hyponatremia and Liver Transplantation: A Narrative Review. Journal of cardiothoracic and vascular anesthesia 2022;36(5):1458-1466. DOI: https://doi.org/10.1053/j.jvca.2021.05.027.

Article of the Month June 2022

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Markmann JF, et al. Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial. JAMA Surg. 2022 Mar 1;157(3):189-198.

Abstract

“Importance: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts.

Objective: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs).

Design, setting, and participants: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list.

Interventions: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital.

Main outcomes and measures: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant.

Results: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant.

Conclusions and relevance: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use.”

Comments by Scott Byram M.D.

Summary:

Normothermic machine perfusion (NMP) is a relatively novel liver preservation strategy as an alternative to the standard, ischemic cold storage (ICS).    In NMP, the donor liver is harvested, the hepatic artery, portal vein, and supra-hepatic cava are cannulated.  Using type specific blood, the portable machine delivers oxygenated blood flow to both the portal and arterial circulations.  The machine and donor organ are then transported to the recipient location for transplantation after several hours of perfusion.   During the perfusion time, oxygenation, arterial and portal pressures, and lactate levels are measured.   NMP may be a viable or even superior method for preservation compared to ICS.  NMP may have the potential to both expand the pool of acceptable organs for transplant, as well as lower the incidence of post-transplant, ischemia-induced cholangiopathy and early allograft dysfunction (EAD). 

                The PROTECT trial1 is a multi-center, randomized clinical trial comparing these two different liver preservation strategies, NMP and ICS.  NMP was accomplished using the Organ Care System (OCS).    The donor inclusion criteria were preselected to capture organs particularly vulnerable to ICS induced damage.  These risk factors included DBD > 40 years old, DCD, macrosteatosis, and expected prolonged ischemic time.  After organ allocation, the donor liver was randomly assigned to either OCS or ICS.  Ultimately, 293 recipients were included in the analysis (151 OCS, 142 ICS).   The groups were similar with the exception of significantly more DCD donors existed in the OCS group.  This potentially reflects that certain marginal grafts were placed on the OCS, which would have been discarded had they been assigned to ICS.  In fact, more than twice as many organs were discarded during procurement in the ICS group due to “clinical judgement” of the surgeon.   The organs in the OCS group were perfused a mean of 276 minutes.  The primary endpoint (EAD) was significantly reduced in the OCS group (18% vs. 31%, p=0.01).  Additionally, ischemic biliary complications were lower in the OCS group compared with the ICS group at 6 months (1.3%vs 8.5%; P = .02) and 12 months (2.6%vs 9.9%; P = .02).  Finally, the authors state that reperfusion syndrome was more severe in the ICS group.  However, this claim was based on post reperfusion lactate levels rather that any hemodynamic parameters. 

                The PROTECT trial is the first trial assessing the superiority of NMP over the standard ICS.  In this study, the authors found that NMP was associated with a lower incidence in early allograft dysfunction and ischemic biliary complications at 6 and 12 months.  Additionally, the use of NMP was associated with an increased number of DCD organs acceptable for transplant.  More studies are warranted; however, NMP appears to be a promising liver graft preservation strategy.

References

  1. Markmann JF, Abouljoud MS, Ghobrial RM, Bhati CS, Pelletier SJ, Lu AD, Ottmann S, Klair T, Eymard C, Roll GR, Magliocca J, Pruett TL, Reyes J, Black SM, Marsh CL, Schnickel G, Kinkhabwala M, Florman SS, Merani S, Demetris AJ, Kimura S, Rizzari M, Saharia A, Levy M, Agarwal A, Cigarroa FG, Eason JD, Syed S, Washburn WK, Parekh J, Moon J, Maskin A, Yeh H, Vagefi PA, MacConmara MP. Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial. JAMA Surg. 2022 Mar 1;157(3):189-198. doi: 10.1001/jamasurg.2021.6781. PMID: 34985503; PMCID: PMC8733869.

Article of the Month May 2022

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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.

References:

  1. 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.

March Article of the Month 2022

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Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study

Abstract

“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.

Summary:

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.

References

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.

April Article of the Month 2022

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Outcome of Liver Transplants Using Donors After Cardiac Death with Normothermic Regional Perfusion.

Abstract:

Background and aims: The incorporation of normothermic regional perfusion (NRP) to donors after cardiac death (DCD) allows the recovery of liver grafts without the deleterious effects on graft survival the super-rapid technique may cause. The aim of the present report is to determine if the use of NRP in Maastricht type III DCD donors achieves short- and medium-term results comparable to donors after brain death (DBD).

Patients and methods: This is an observational cohort study including 117 liver transplants executed between November 2016 and April 2021, divided into NRP (n = 39) and DBD (n = 78).

Results: Donors were younger in the NRP group (NRP 52 vs DBD 59.4 years; P < .005). Liver recipients in each study group were of similar age and severity of liver disease, although the predominant transplant indication in the NRP group was hepatocellular carcinoma. No differences in ischemia times were found. The incidence of early allograft disfunction and primary nonfunction was balanced between NRP and DBD. Eight patients required retransplant, all of them in the DBD group. No differences were found in biliary complications (NRP 12% vs DBD 5%; P = .104). Ischemic cholangiopathy affected a single DBD patient. Graft survival’s Kaplan Meier curve shows a better outcome in the NRP group, although the difference did not reach significance (P = .075).

Conclusions: The incorporation of perfusion machines, and specifically the NPR in situ, converts suboptimal liver grafts such as DCD into organs comparable to DBDs.

Comments made by Cale Kassel M.D., FASA  

Summary:

In this observational cohort study the authors compared the use of normothermic regional perfusion (NRP) in donation after cardiac death (DCD) donors to donation after brain death donors (DBD). A total of 117 liver transplants were included, 39 in the NRP group and 78 in the DBD group.

Donors for the two groups were largely similar we a few exceptions. Donor age was lower in the NRP group (52 vs. 59.4; p = 0.005). While the number of days in the ICU was higher in the NRP group (7.21 vs. 2.62; p = 0.000), the use of vasopressor support was higher in the DBD group (86.4% compared to 35.1%). 

Recipient differences were similar for MELD scores for the NRP and DBD groups. (14.48 vs. 16.14; p = 0.392). The authors noted differences in indication for transplant between the two groups. For DBD, alcoholic cirrhosis was the most common indication followed by hepatocellular carcinoma. In the NRP group, hepatocellular carcinoma was the most common indication. 

No primary endpoint was noted but overall survival was similar between the two groups. One year survival for the NRP group as 94% compared to 84% in the DBD group and at three years, survival was 71% for the NRP group and 75% for the DBD group. While the Kaplan-Meier curve showed better survival with the NRP group, this did not reach statistical significance (p = 0.075). Biliary complications were not statistically different between the two groups (NRP at 12%, DBD at 5%). Early allograft dysfunction, primary non-function, and acute kidney injury were similar between the two groups. 

With constant need for donor organs, new ways to procure organs for transplant warrant consideration. Early evidence raised concerns on the rate of biliary complications with DCD donors that may limit their usefulness. However, NRP or machine perfusion appears to offer promise for DCD organ use while also minimizing biliary issues post-operatively. This small study adds to the body of evidence supporting the use of NRP for DCD organs. 

References:

Rodriguez RP, Perez BS, Daga JAP, et al. Outcome of Liver Transplants Using Donors After Cardiac Death with Normothermic Regional Perfusion. Transplantation proceedings 2022;54(1):37-40.

February 2022 – Article of the Month

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Is Obesity Associated with Better Liver Transplant Outcomes? A Retrospective Study of Hospital Length of Stay and Mortality Following Liver Transplantation. Anesthesia and Analgesia. 2022.

Abstract:

Background: The rise in obesity in the United States, along with improvements in antiviral therapies, has led to an increase in the number of obese patients receiving liver transplants. Currently, obesity is a relative contraindication for liver transplant, although exact body mass index (BMI) limits continue to be debated. Studies conflict regarding outcomes in obese patients, while some argue that BMI should not be used as an exclusion criterion at all. Therefore, this retrospective study-utilizing a large national database-seeks to elucidate the association between recipient BMI and hospital length of stay and mortality following liver transplant.

Methods: A retrospective study was conducted using the United Network for Organ Sharing Standard Transplant Analysis and Research database. Fine-Gray competing risk regressions were used to explore the association between BMI and rate of discharge, which varies inversely with length of stay. In our model, subdistribution hazard ratio (SHR) represented the relative change in discharge rate compared to normal BMI, with in-hospital death was considered as a competing event for live discharge. Cox proportional hazard models were built to assess the association of BMI category on all-cause mortality after liver transplantation. Cluster-robust standard errors were used in all analyses to construct confidence intervals.

Results: Within the final sample (n = 47,038), overweight (≥25 and <30 kg/m2) patients comprised the largest BMI group (34.7%). The competing risk regression model showed an association for increased length of stay among underweight (SHR = 0.82, 95% confidence interval [CI], 0.77-0.89; P < .001) and class 3 obesity patients (SHR = 0.88, 95% CI, 0.83-0.94; P < .001), while overweight (SHR = 1.05, 95% CI, 1.03-1.08; P < .001) and class 1 obesity (SHR = 1.04, 95% CI, 1.01-1.07; P = .01) were associated with decreased length of stay. When the sample excluded patients with low pretransplant functional status, however, length of stay was not significantly shorter for overweight and obesity class 1 patients. Cox proportional hazard models demonstrated increased survival among overweight, class 1 and class 2 obesity patients and decreased survival among underweight patients.

Conclusions: Our results provide evidence that overweight and obesity class 1 are associated with decreased length of stay and mortality following liver transplant, while underweight and obesity class 3 are associated with prolonged length of stay. Pretransplant functional status may contribute to outcomes for overweight and class 1 obese patients, which necessitates continued investigation of the isolated impact of BMI in those who have had a liver transplant.

Comments made by Cale Kassel M.D., FASA  

Summary:

In this retrospective study1 examining obesity in liver transplant patients, the authors utilized data from the Scientific Registry of Transplant Recipients (SRTR) to compare obesity class and hospital length of stay (LOS) and mortality. With nonalcoholic steatohepatitis (NASH) set to become the leading indication for LT, providers must consider the risks of transplantation in obese patients. With conflicting data on the risk of obesity in LT, this is usually a center-specific guideline on listing patients with elevated BMI. A total of 47,038 patients were reviewed and divided into 6 groups (underweight, normal, overweight, obese I, obese II, and obese III).

Compared to normal weight patients, hospital LOS was lower in the overweight and class I obesity group while it was longer in the obese III and underweight groups. Further risk analysis that excluded patients with hospitalization prior to transplant, functional status < 50%, mechanical ventilation still demonstrated longer LOS with underweight and obese III groups.

At 90 days, survival was lowest in the underweight and class III obesity group of patients (95.5%, 94.1% respectively). Survival at 1 year and 10 years were lowest in the underweight group of all groups studied. Interestingly, the class I obesity group had the best 1-year and overall survival by the unadjusted Kaplan-Meier model.

The retrospective nature of the study and the presence of ascites are both limitations interpreting the data. Factoring in ascites in the body weight calculation can be challenging and may have led to overrepresentation of obese patients in this study.

Ultimately, the authors found shorter LOS in overweight and class I obesity. Both underweight and class III obesity had longer LOS. Further research into this topic is needed to evaluate the role of functional status in obesity and outcomes. For programs looking to identify specific cutoffs, the authors suggest, based on their findings, that many centers may benefit from a BMI cutoff of > 40 kg/m2.  It should be noted that both the AASLD and AST consider class III obesity as a contraindication for LT. The EASL suggests careful evaluation of patients with a BMI > 35 kg/m2.

References:

  1. Du AL, Danforth DJ, Waterman RS, Gabriel RA. Is Obesity Associated with Better Liver Transplant Outcomes? A Retrospective Study of Hospital Length of Stay and Mortality Following Liver Transplantation. Anesthesia and Analgesia. 2022.

January 2022 – Article of the Month

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Postreperfusion syndrome in liver transplantation: Outcomes, predictors, and application for recipient selection. Clinical Transplantation. 2022.

“Background: This study aimed to identify risk factors for postreperfusion syndrome (PRS) and its impact on LT outcomes.

Methods: Data analysis was performed in 1021 adult patients undergoing donation after brain death (DBD) LT to identify PRS incidence, the risk factors for PRS development, and its impact on LT outcomes.

Results: The overall incidence of PRS was 16.1%. Independent risk factors for PRS included donor age (odds ratio (OR) 1.01, P = .02), donor body mass index (BMI) (OR 1.04, P = .003), moderate macrosteatosis (OR 2.48, P = .02), and cold ischemia time (CIT) (OR 1.06, P = .02). On multivariable analysis for 30-day graft failure, PRS (hazard ratio (HR) 3.49; P < .001) and Model for End-stage Liver Disease (MELD) score (HR 1.01; P = .05) were independent risk factors. Patients were categorized into four distinct groups based on PRS risk groups and MELD groups, which showed different 1-year graft survival (P < .001). There were comparable outcomes between low PRS risk – high MELD and high PRS risk – low MELD group (P = .33).

Conclusions: Donor age, donor BMI, moderate macrosteatosis, and CIT were identified as risk factors for the development of PRS in LT using DBD grafts. PRS risk evaluation may improve donor-to-recipient matching based on their MELD scores.”

Comments made by Cara Crouch, MD  

This article conducted a retrospective review of all adult DBD liver transplants from a single center over a 15-year period, excluding patients who received multi-organ transplants, DCD grafts, split grafts, LDLT, retransplant and patients who were transplanted due to acute liver failure, to identify risk factors for the development of postreperfusion syndrome (PRS). The authors also reviewed outcomes and offer suggestions for donor/recipient matching to reduce the incidence of PRS. The authors defined PRS as “a >30% decline in mean arterial pressure (MAP) from baseline within 5 minutes of graft reperfusion and lasting at least 1 minute.” A total of 1021 cases were reviewed and the overall incidence of PRS was found to be 16.1%.

The authors found no recipient factors that were statistically significant for an association with PRS. Four donor factors were found to be independently associated with PRS: donor age, donor BMI, moderate macrosteatosis (30-60%) and cold ischemia time. The authors used this data to develop a PRS risk sore used to categorize patients as either low or high PRS risk.

Patients also underwent further risk stratification, low ( 25) vs. high (>25) MELD, in combination with low vs. high PRS risk to analyze graft and patient survival. The occurrence of PRS was found to be associated with worse short-term graft and patient outcomes but not long-term outcomes. When PRS risk and MELD score were combined, it was found that patients with high MELD and high PRS risk factors had poor outcomes. The authors suggest that identifying the PRS risk factors and utilizing the risk score may allow for more optimal donor/recipient matching to improve overall outcomes.

References:

1. Bekki Y, Myers B, Wang R, Smith N, Zerillo J, Rocha C, Tabrizian P, Moon J, Arvelakis A, Facciuto M, DeMaria S, Florman S. Postreperfusion syndrome in liver transplantation: Outcomes, predictors and application for recipient selection. Clinical Transplantation. 2022.