Conference Report: Anaesthesia/Critical Care Sessions
at the 2012 ILTS Annual Congress, San Francisco, USA
There were 3 Anaesthesia/Critical Care sessions at the 2012 ILTS conference in San
Francisco. The first was a featured symposium which consisted of 3 interesting
presentations relating to the optimization of the transplant donor patient and graft. The
second was an oral presentation session of 6 abstracts covering various topics of interest
in liver transplant anaesthesia. The third session was an interactive oral abstract
presentation session which covered predominantly pre-transplant work up and cardiac
topics.
Below is a synopsis of each session:
Featured Symposium: Anaesthesia/Critical Care medicine – Patient and Graft
Optimization
The theme of the featured Anaesthesia/Critical Care Medicine symposium at ILTS was
"patient and graft optimization". It was well attended and consisted of 3 interesting
presentations by intensivists and surgeons in organ procurement.
First Presentation - “In vivo Optimization: Donor Management Goals (DMGs) What’s in for
the liver?” by Dr DJ Malinoski from Cedars-Sinai hospital, Los Angeles, CA, USA
The American National average of organ donation per donor patient (OTPD) at present is
3 organs. Inconsistent donor management practices may be a reason for the low number
of organs procured. The use of a standardized organ donor checklist has been advocated
as a step forward in improving organ procurement.
Region 5 Donor management Goals (DMGs) initiative looked at retrospective data from
2007-2008 and showed that achieving at least 8 DMGs was associated with more organs
transplanted per donor. When DMGs are met, 70% of organ transplantation were
achieved. DMGs include mean arterial pressure (MAP), central venous pressure (CVP),
ejection fraction (EF), vasopressor use, arterial blood gas pH, PaO2: FiO2, serum Na,
blood glucose, haemoglobin and urine output. In a Phase 2 prospective study from June
2008-2009, it was found that when more than 7 DMGs were met, there were > =4 organs
transplanted per donor.
The speaker also stated that graft function is probably a better assessment of better donor
patient management instead of organs transplanted per donor and meeting DMGs was
shown to be associated with improved graft function in kidney transplants.
Data analysis from June 2008-2011 of 961 DNDDs showed that liver graft utilization rates
are higher when DMGs are met. Conversely, when donor liver is transplanted, the total no
of DMG values of MAP, CVP, etc met were higher. Other factors thought to be influencial
include use of thyroid hormone and vasopressin, younger age and a lower BMI.
The speaker concludes that 1) meeting DMGs is associated with higher Organs
Transplanted per donor patient (OTPD) and improved graft utilization, 2) care by hospital
makes a difference and a higher organ utilization rate is associated with lower donor age
and low BMI.
Second presentation - “Ex vivo optimization: thinking outside the box” by Prof J V Guarrera
from Columbia University, New York, NY, USA.
Innovative strategies for safe utilization of marginal livers are needed because of the low
supply of donor organs and there is an increasing demand for improvements in organ
preservation.
The current data show deceased cardiac donors (DCD), steatotic and elderly donor livers
are most susceptible to significant injury and assessment of donor liver is predominantly
based on assessment of appearance in the cooler box and/or biopsy of the donor liver at
the recipient centre. Usually, if strategies are too conservative, many donor organs will be
wasted but too aggressive an approach has been associated with inferior centre outcomes
and may be subjected to regulatory body enquiries
In DCD donors, the difficult to manage conditions include ischaemic cholangiopathy and
intra-Hepatic Biliary Strictures. Strategies which have been suggested to be helpful in
improving utilization and outcome of the donor organ include:
1) minimizing cold and warm ischaemic time
2) avoiding older DCDs - cutoff 50?
3) in situ biliary flush to minimize bile induced epithelial damage
4) patient selection
5) simultaneous arterial revascularization with portal vein or reperfusing the artery
first
ECMO resuscitation of the donor patient may be helpful because it minimizes ischaemic
time and allows time for metabolic resuscitation and viability testing of the donor organ.
The speaker then introduced the Liver Hypothermic Perfusion machine and stated the
following advantages:
1) mitigation of ischaemic reperfusion injury
2) better preservation of microvasculature of the donor liver
3) allowance for administration of pharmacological and genetic (future) therapy
This machine has been used on Steatotic livers and grafts which have been rejected by
other centre. In phased trials all 35 grafts were transplanted successfully and the results
were comparable to benchmarks. Machine perfusion donor livers had better microscopic
structures and less activated kipper cells. It has also been shown that there is better bile
duct preservation with ex vivo organ perfusion.
Other options available for ex-vivo organ optimization include:
1) normothermic perfusion – however, when compared to hypothermic perfusion,
the stakes are higher if the equipment fails and there is higher risk of infectious
disease transmission
2) exvivo defattening of Steatotic liver
Third presentation - “Recepient optimization: pharmacological preconditioning” by Prof P
Schemmer from Heidelberg University Hospital, Heidelberg, Germany.
The main problem that is faced in transplantation is that of organ dysfunction ie. primary
dysfunction and primary non function of the graft, which can happen up to 80% of the time.
Pharmacological agents that are thought to be useful in reducing the incidence of organ
dysfunction include glycine, taurine, melatonin and NO and these may be given to the
recipient and the donor.
Glycine is thought to open chloride channels and prevent changes associated with
reperfusion injury by preventing the influx of calcium and activation of TNF alpha, NO.
Glycine and Taurine are also thought to prevent kuppfer cells activation and this can result
in improved microcirculation and decreased serum liver enzymes which may be
associated with increased survival of the graft. A trial involving preconditioning of liver
transplant patients with 8gm of glycine showed improved function in trial patients.
Melatonin is an endogenous radical scavenger and has been shown to inhibit IkK and JNk
pathways
A dose of 50mg/kg BW po 2 hours before warm ischaemia has been shown to increase
survival of the graft.
Inhaled NO in a prospective trial of patients undergoing orthotopic liver transplant has
been shown to be beneficial in accelerating liver graft function and decreased length of
stay in hospital.
Asian substances such as Danzhen and green tea have too been shown toimprove
survival after liver transplantation in small animal models.
Another intervention of benefit to the recipients listed for transplantation is improvement in
the preoperative care of long term immuno-nutrition.
The speaker concludes that pharmacological manipulation can be useful to improve graft
function and should be started in donors (if possible) and recipients.
Write up II -Concurrent Abstract Session
There were 6 well presented oral abstracts covering different topics of interest in liver
transplant anaesthesia during this session.
1. Markers of cirrhotic cardiomyopathy in liver transplant candidates by Dr J
Findlay.
Actual prevalence of cirrhotic cardiomyopathy (CCM) is unknown and there is no definite
diagnostic criteria as yet.
Electrocardiographic and echocardiographic variables potentially indicative of CCM in 368
successive LT candidates were reviewed. Mean age was 52+/- 10yrs, MELD 14.9+/-8.
Diastolic dysfunction was present in 62% of resting echocardiography, 10% had low
ejection fraction (<55%), and 24% had QTc prolongation.
When stratified to low and high MELD scores, it was found that the incidence of prolonged
QTc, increased LA volume and failure to achieve heart rate with stress was higher in the
high MELD group.
Conclusion
The finding of diastolic dysfunction being vey common in liver transplant patients is
consistent with the literature. Prolonged QTc, increased LA volume and inappropriate
heart rate response to stress are associated with worsening liver failure and may identify
significant CCM.
2. Size adjusted peak ASTi has better predictive value for primary Graft non function
than conventional UNOS criteria in ortho topic liver transplantation by Dr K
Fukazawa.
The Size adjusted peak ASTi is calculated by Peak AST(within 7 days)/BSAi (BSAi =
BSAdonor/BSArecipient).
Data on 930 OLT patients was reviewed. It was found that ASTi>3500 and PT-INR >2.3
had higher sensitivity and specificity compared to UNOS criteria and can be more reliably
used to predict subsequent PNF/graft failure.
Conclusion
ASTi can be a simple, reproducible and sensitive clinical marker of early graft damage in
OLT.
3 Association between Nitric oxide dysregulation and haemodynamic instability
during liver graft reperfusion in patients with End Stage Liver Disease by Dr D
Bezinover
After analyzing blood samples from 44 patients undergoing LT, it was found that in
patients with increased catecholamine use for liver graft reperfusion, there is a statistically
significant higher level of cGMP (second messenger of nitric oxide) in the portal vein than
the radial artery preoperatively, before reperfusion, 20mins after reperfusion and also in
flush blood.
Conclusion
An increased nitric oxide level among other factors may contribute to haemodynamic
instability during liver graft reperfusion and the preoperative level of cGMP may be a
predictive factor.
4. Safety of intraoperative haemodialysis during liver transplantation: a 10 year
experience by Dr L Matsuoka
This is a retrospective study of 175 liver transplant patients who received intraoperative
HD from 2001-2011 at a single centre and the finding was that intraoperative
haemodialysis can be performed safely, efficiently and with haemodynamic tolerability in
liver transplant patients. The long term dialysis dependency rate was low.
Questions of concern with intraoperative haemodialysis include:
1. Hypothermia associate with dialysis
2. Tendency for thrombosis
5. Postoperative changes in coagulation parameters in 210 patients undergoing liver
donor hepatectomies: implication for epidural analgesia by Dr GV Premkumar
Retrospective observational study in 210 patients who underwent living donor liver
transplant hepatectomies from June 2010 to May 2011 and received epidural analgesia,
showed that most live liver donors experienced a post operative coagulation derangement
that correlated with the amount of liver removed. It was also found that epidural catheters
were safe in all donors and could be removed after the correction of coagulation
derangement by day 6 in all patients.
TEG may be a good way of looking at coagulation profile after donor hepatectomies.
6. Blood product usage and fibrinolysis in liver transplantation before and after
cessation of aprotinin by Dr N Schofield
A retrospective analysis of 200 patients - 100 in aprotinin group and 100 post aprotinin
group was undertaken. It was found that there was no significant change in blood product
usage despite the fact that aprotinin was no longer given prophylactically. The study
suggests that antifibrinolytic therapy is best targeted in patients in which fibrinolysis has
been proven.
Write up III - interactive oral abstract presentation
This interactive oral abstract presentation was chaired by Dr J Klinck and Dr R Steadman
and covered interesting and at times controversial topics in pre transplant workup. There
was lively audience participation during Q&A and the interactive question polling session
at the end of each presentation.
1. Preoperative Transthoracic Echocardiography does not predict intraoperative
systolic pulmonary artery pressure in liver transplant candidates by Dr A Sharma
A retrospective study of 397 liver transplant patients found that preoperative RVSP of
more than 30mmHg was a poor predictor of intra-operative systolic pulmonary artery
pressure.
2. Should ICU admission after liver transplantation be mandatory? Fast tracking to
the surgical ward following liver transplantation by Dr B Taner
A retrospective study of 1045 liver transplant patients between 2003 to 2007 showed that
fast tracking of select patients to the surgical ward after LT can be done effectively and
safely. Suitable patients include those with shorter duration of surgery, lower intraoperative blood transfusion, lower raw MELD score and younger recipient age.
3. Myocardial Perfusion imaging is frequently useless in the preoperative evaluation
of liver candidates by Dr A Toussaint
A single centre analysis of Myocardial Perfusion Imaging (MPI) performed as preoperative
coronary artery disease screening showed that MPI are frequently not useful due to
inability to achieve maximal predicted heart rate and failure of temporary stoppage of beta
blocker. Severity of hepatic disease and hyper dynamic circulatory state in cirrhotic
patients are also thought to be important factors.
4. Coronary Artery Disease in OLT recipients: An update on Outcomes by Dr C Wray
A multicenter retrospective analysis of mortality in angiogram proven Coronary Artery
Disease (CAD) showed that current preoperative cardiac optimization and treatment
confers equal survival benefits for liver transplant (LT) when compared to CAD negative
patients. This is in contrast to previous study findings of poor survival outcomes in LT
patients with advanced CAD by Plotkin (1996).
5. Aorto-Right Atrial Fistula Per Transoesophageal Echocardiography during Redo
Liver Transplantation by Dr W Soong
This presentation of a rare case of aorta-right atrial fistula found on TEE and the
successful management of this difficult problem adds to growing evidence in support of
routine use of TEE as an intraoperative monitor in OLT.
6. Budd-chiari Syndrome requiring Heparin Infusion during Liver Transplantation
(LT) by Dr Y Morita
This case presentation of a primary budd chiari syndrome highlights the often
unrecognized hyper coagulate state in such patients. Heparin infusion with coagulation
monitoring can be recommended to prevent vascular thrombosis of graft and embolisms of
pre existing thrombosis in such patients.
7. Pre-Operative Optimization – Is this the Best we can expect by Dr A Walia
This was an interesting case presentation, illustrating the importance of aggressive
preoperative optimisation of liver transplant patients to prevent them from being in a too
sick to transplant situation.
8. A presentation of data on intraoperative cardiac arrests during orthotopic liver
transplantation over 10 years by Dr A Iqbal
This presentation of a single UK hospital's data on intraoperative cardiac arrests during
OLT over 10 years showed that most cardiac arrests were related to reperfusion
hyperkalaemia. Possible associated factors include donor BMI, degree of portal
hypertension in recipients, the preservation solution used, and techniques of flushing the
donor livers.
Prepared by
Dr Terry Pan
Clinical Fellow, Liver Transplant Anaesthesia
Addenbrookes Hospital, Cambridge University Health Service
Cambridge, United Kingdom