Liver Failure Clinical Trial
Official title:
Use of Cerebral Oximetry In Adult Chinese Patients For Liver Transplantation
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver diseases. Although with continuous advancement in technology, it remains a high-risk operation. The goal of LT is not only ensure survival of the patients but also to restore them back to their pre-morbid state with a good quality of life. Neurological sequelae can have major impact on postoperative outcomes after LT and yet the reported literature is scarce. Studies from Western countries showed some evidence on the use of cerebral oximtery in cardiac surgery to prevent neurological mishaps. LT shares similar intra-operative fluctuation of the haemodynamices as in cardiac surgery, causing disturbances in regional cerebral oxygenation and theorectically cerebral oximetry should be of great value as well in LT surgery. Data from a large randomised controlled trial is lacking from the current literatures. We therefore propose a prospective randomized controlled trial on the use of this device in adult LT and see whether its use could reduce neurological mishaps.
Liver Transplant Liver transplantation (LT) is a life-saving procedure for patients with
end-stage liver disease. Despite continuous advancement in technology, it remains a high-risk
operation. The building-up of an oxygen debt during LT can lead to an increased risk of poor
postoperative outcomes (1, 2). Furthermore, patients with acute liver failure or end-stage
liver disease are prone to hepatic encephalopathy, which can lead to disturbance of
auto-regulation in the brain, which may eventually cause cerebral hypoxia and ischaemia.
Irresversible metabolic disturbances can impair cerebral auto-regulation, causing poor
neurological outcomes after LT (3). The prevalence of encephalopathy, delirium and stroke in
transplant recipients is 12-40% (3). Hypotheses for these conditions include prolonged stay
in the intensive care unit (ICU) (so-called "ICU psychosis"), the use of Tacrolimus (4),
rapid correction of hyponatraemia (5) and impaired cerebral auto-regulation (3), but no
definite conclusion can be made most of the time. Among these hypotheses, impairment of
cerebral auto-regulation has never been documented in large clinical trials for Chinese
patients in LT.
Cerebral oximetry (Near infra-red spectroscopy, NIRS) There is no "gold standard" for
measuring cerebral auto-regulation. Monitoring of the brain oxygenation, such as direct
tissue O2 tension and jugular bulb O2 saturation, has been used as a surrogate of
auto-regulation but it is invasive. Transcranial laser Doppler (TCD) of the middle cerebral
artery has been validated in healthy volunteers as well as real patients as a good
measurement of cerebral blood flow (6, 7). Similarly, near-infrared spectroscopy (NIRS), a
non-invasive and continuous method, can also monitor the regional cerebral oxygenation
(rScO2) and is increasingly used in cardiac surgery. A previous report has validated the use
of NIRS when compared to TCD, as the latter requires a trained technician to monitor and
supervise. NIRS provides a timely, real-time, inexpensive, easily measurable alternative to
TCD, and thus should have a great potential for clinical usage in LT. Similar to other
non-invasive oximetry (e.g. pulse oximetry), measurement can be done through adhesive tapes
over bilateral forehead and connected to the machine (INVOS™ 5100C Cerebral/Somatic Oximeter
by Covidien). This system is the ONLY cerebral/somatic oximetry system with FDA cleared
improved outcome claims (8). Plachky et al. showed that 50% of patients demonstrated a
decline in cerebral oxygen saturation when clamping of the vessles during LT and it had
positive correlation with the postoperative cerebral disrubances (9). Nonetheless, the
clinical application for patients undergoing LT is scarce and its application is novel. The
use of this technology may potenitally be limited by the presence of high levels of bilirubin
acting as a chromophore interferring with its data acquistion. However, in a pilot study of 9
patients who underwent LT investigators using this technology were able to demonstrate that 3
out of 9 patients had either transient or persistent impaired auto regulation throughout the
operation. This in turn was associated with higher Model of End-Stage Disease Score (MELD)
>15 (p=0.015), more postoperative seizures and stroke (P<0.0001) (3). A recent systematic
review (10) of 901 Caucasians from 24 publications showing a decrease in NIRS (>15% relative
to baseline) could have impaired postoperative cognitive function (28 versus 26; MMSE) and
reduced LOS (14 versus 23 days) in open surgery. In the field of LT, impaired cerebral
autoregulation (25%), cerebral deoxygenation in the anhepatic phase (36%) and cerebral
hyperoxygenation with reperfusion of the grafted liver (14%) were identified by NIRS and
could lead to adverse neurological outcome such as seizures, transient hemiparesis and
stroke. Nonetheless, no large prospective randomized trial and no Chinese cohort were
included.
References
1. Shoemaker WC, Appel PL, Kram HB. Role of oxygen debt in the development of organ failure
sepsis, and death in high-risk surgical patients. Chest. 1992;102(1):208-15.
2. Shoemaker WC, Appel PL, Kram HB. Hemodynamic and oxygen transport responses in survivors
and nonsurvivors of high-risk surgery. Critical care medicine. 1993;21(7):977-90.
3. Lescot T, Karvellas CJ, Chaudhury P, Tchervenkov J, Paraskevas S, Barkun J, et al.
Postoperative delirium in the intensive care unit predicts worse outcomes in liver
transplant recipients. Can J Gastroenterol. 2013;27(4):207-12.
4. DiMartini AF, Trzepacz PT, Pajer KA, Faett D, Fung J. Neuropsychiatric side effects of
FK506 vs. cyclosporine A. First-week postoperative findings. Psychosomatics.
1997;38(6):565-9.
5. Lee J, Kim DK, Lee JW, Oh KH, Oh YK, Na KY, et al. Rapid Correction Rate of Hyponatremia
as an Independent Risk Factor for Neurological Complication Following Liver
Transplantation. Tohoku J Exp Med. 2013;229(2):97-105.
6. Lang EW, Mehdorn HM, Dorsch NW, Czosnyka M. Continuous monitoring of cerebrovascular
autoregulation: a validation study. Journal of neurology, neurosurgery, and psychiatry.
2002;72(5):583-6.
7. Ono M, Zheng Y, Joshi B, Sigl JC, Hogue CW. Validation of a stand-alone near-infrared
spectroscopy system for monitoring cerebral autoregulation during cardiac surgery.
Anesthesia and analgesia. 2013;116(1):198-204.
8. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, et al. Monitoring
brain oxygen saturation during coronary bypass surgery: a randomized, prospective study.
Anesthesia and analgesia. 2007;104(1):51-8.
9. Plachky J, Hofer S, Volkmann M, Martin E, Bardenheuer HJ, Weigand MA. Regional cerebral
oxygen saturation is a sensitive marker of cerebral hypoperfusion during orthotopic
liver transplantation. Anesth Analg. 2004;99(2):344-9.
10. Sorensen H, Grocott HP, Secher NH. Near infrared spectroscopy for frontal lobe
oxygenation during non-vascular abdominal surgery. Clin Physiol Funct Imaging.
2016;36(6):427-35.
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