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1. Perioperative Challenges of the Small Liver Transplant Recipient Judith E. Brill, M.D.
Professor of Pediatrics & Anesthesiology
Chief, Division of Critical Care
Director, Pediatric Intensive Care Unit
Vice Chairman for Clinical Affairs, Dept. of Pediatrics
Mattel Children’s Hospital at UCLA Medical Center
2. Size & Young Age Are No Obstacle to Liver Transplantation Small patients represent a large percentage of patients undergoing OLT
UNOS 2001: 623 pediatric OLTs
167 children < 1 year
8 in neonates (0-3 mos.)
UCLA 1999- June 1, 2005: 60 babies (<1 year of age) were transplanted in 77 months
3. OLT in Small Pediatric Patients Development of reduced-size liver transplantation(segment II & III or monosegment grafts) & living-related OLT extends OLT to many small infants who would otherwise die awaiting size-matched grafts
Biliary atresia usually most frequent indication for OLT except in babies 0-3 months
4. Survival in Small OLT Patients(Sundaram et al. Liver Transplantation 2003. 9:783) UNOS: Children over 6 years have graft & patient survival 82% & 92% respectively
UNOS: Children 1-5 years have graft & patient survival 76.8% & 84.1%
UNOS: Infants 3 to 12 months have graft & patient survival 72.8% & 82.1% respectively
UNOS: Neonates (0-3 mos.) have graft & patient survival of 38% & 57%
5. Survival: Other Reports OLT in 16 infants <7 kg (13 <1 yr): overall survival 82%, graft survival 72%
Lopez et al. Pediatr Transplantation 2004. 8:228
What accounts for reduced survival in some series of patients <1 year?
Development of vascular thrombosis (especially in full-size grafts)
Donor weight under 6 kg
Mortality appears to be improving as reported in most more recent reports
6. Improving Mortality in Pediatric Liver Transplantation Better survival of infants <1 year age after 1993 vs 1984-1993: attributed to increased experience of entire team including surgeons, pediatric gastroenterologists & intensivists, RNs, etc.
Goss et al. Ann Surg 1998;228:411
Cause of liver failure matters: worse outcome (60% 1-year survival) seen in neonatal idiopathic hepatitis (various infectious/metabolic causes), iron storage disease, etc.
Woodle et al. Transplantation 1998;66:606
7. Survival of UCLA Patients Transplanted < 1 Year of Age 1999 to present: 74 grafts in 60 patients before age 1 year
47 patients received single graft
12 patients received two grafts
1 patient received three grafts
48 children currently alive for 80% survival to date
8 of 12 non-surviving babies died within 100 days of transplantation (average 26.5 days)
8. Recent UCLA Experience with Small OLT Patients Surviving Patients Who Received Single Graft: 39
PICU Days averaged 14.3 (range 3-57 days)
Ventilator Days averaged 12.7 (range 1-56 days)
Days from transplant to discharge from hospital averaged 32.9 (range 12-111 days)
9. Babies Receiving 2 Grafts in 1st Year of Life 6 of 12 recipients have survived
PICU Days: average 68.3 (range 12-136)
Ventilator Days: average 55.3 (range 6-129)
Days from OLT to discharge (5 patients; 1 still in-house): 108 (range 22-188)
2 recipients of 3 grafts expired
1 at 4 ½ yrs of age
1 who received all 3 grafts in 1st year of life died at 11 ½ months of age
10. Non-Surviving Small OLT Recipients at UCLA 1999-mid 2005: 12 patients of 48 have expired
5 received a single transplant
5 received 2 transplants
1 received 3 transplants before age 1
1 received 3 transplants (2/3 after age 1)
8 died in 1st year of life (within 100 days)
4 died after 1st year of life (range age 13 months to 47 months following OLT #1)
11. Death Following OLT in Small Patients Main reasons for death cited:
SEVERE INFECTIONS/SEPSIS (WITH MOSF)
HEMORRHAGE
VASCULAR THROMBOSIS
PRIMARY NONFUNCTION
SPLIT Research Group. Transplantation 2001;72:463
Jain et al. Transplantation 2002;73:941
Cacciarelli et al. Transplantation 1997;64:242
12. Features of Note Regarding Small OLT Recipients Some small, young OLT recipients do remarkably well following transplant: e.g., 5.9 kg, 5 ¾ mo. old baby w/ cryptogenic cirrhosis 2o biliary atresia extubated POD# 1, out of PICU POD#5, home POD#31
Difficult to predict which patients will have an easy post-operative course, which will not
13. Features of Note in Small OLT Recipients: Nutrition Concerns perioperatively include:
Poor nutrition, poor weight gain despite provision of adequate calories
Feeding difficulties common & contribute to lengthy post-op stays
Consider secure (permanent) central access early, particularly if TPN needed
Ensure ample support to resolve post-op feeding difficulties (OT, feeding teams etc.)
Catch-up growth usually excellent post-OLT
14. Features of Note in Small OLT Recipients: HAT Hepatic Artery Thrombosis (HAT): dreaded vascular complication
Infants <1 yr at greater risk (rates of 4-26% reported)
Cacciarelli: All thrombotic events (14%) occurred in infants <12 months of age
Goss: 12.5%; SPLIT 9.7% all children
Highest rate (33%) seen in recipients of full-sized grafts from donors weighing <6 kg
15. Risk of Vascular Thrombosis Following OLT Relative risk of thrombosis for graft type:
Full-sized grafts higher (21%)
Reduced-size grafts (8%)
Risk factors: long cold ischemia time; use of whole graft with low recipient hepatic arterial inflow
Anticoagulation (heparin/coumadin); anti-aggregants (ASA/dipyridamole); dextran (lowered viscosity) used: ??? Not proven to lower rate of vascular thrombosis
16. Diagnosing Vascular Complications in OLT Be highly suspicious & vigilant for detection of HAT:
Frequent accessible doppler ultrasound
Willingness to explore patient where vascular compromise suspected
BEING SUSPICIOUS that HAT may be present in baby with persistent transaminitis, poor weaning from ventilator, metabolic acidosis, rising white count, fever, or who “just doesn’t look right”
17. Ventilator Dependence in Small OLT Recipients Many small children appeared to become “marooned” on the ventilator!
UCLA: 48 surviving babies averaged 22.2 ventilator days
Range: 3 children ventilated 1 day, 22 ventilated 2-5 days, 15 over 28 days
8 children were ventilated >50 days (longest: 129 days)
18. Ventilator Dependence in Small OLT Recipients 3 of 48 survivors required tracheostomy for chronic respiratory insufficiency, upper airway obstruction
BAFK, OLT #1 age 11 ½ mo., OLT #2 age 12 ½ mo.
Congenital hepatic fibrosis, Trisomy 21, OLT age 2 mo. Weight 4.22 kg
Neonatal hepatitis (Echovirus?) OLT age 2 ½ mo. Weight 7.3 kg
Post trach: babies were more easily weaned from ventilatory support
19. Ventilator Dependence: Contributing Factors Poor nutritional state pre-op; inanition
Atelectasis
Hemidiaphragm hemiparesis or paralysis
Diaphragmic embarrassment due to large graft
Abdominal closure over large graft
20. Ventilator Dependence Does donor size matter?
Barcelona group: mean weight ratio between donor & recipient 5.27
Important to avoid compression of graft or right lung
Strongly recommend temporary abdominal closure (silastic patch, mesh etc. as needed) to avoid tightness
Lopez et al. Pediatr Transplantation 2004:8:228
21. Ventilator Dependence Barcelona group: no problems with delayed abdominal closure; no increase in wound infections
Recommend monitoring intra-abdominal pressure, especially if child ventilated
Bladder pressure their method of choice: cut-off >15-20 mm Hg
Measurement of CVP also helpful
22. Weaning from Ventilatory Support: It is hard to be patient! Weaning more likely to be successful if:
Patient in good fluid balance, well-diuresed
Electrolytes normal (especially K, Mg)
Patient in + nitrogen balance, well-nourished
Atelectasis resolved; no bronchospasm
Patient afebrile without new infection
23. Weaning from Ventilatory Support Helpful strategies:
Sprinting patient to re-condition respiratory musculature
Using pressure support to overcome work of breathing (WOB)
Transitioning to Vapotherm (high flow therapy humidified) to reduce WOB after extubation
Considering non-invasive ventilation for marginal patients after extubation: bilevel PAP (BIPAP) & pressure support
24. Perioperative Challenges in Care ofNeonates (0-3 months) Undergoing OLT
Body weight typically 3.5-4.5 kg (smallest 2.4 kg; youngest 5 days)
Average OLT neonate similar in size to normal newborn but babies in liver failure have abnormal body mass distribution
Intrinsic physiology of neonate in liver failure contributes to high rate of operative & post-op complications
Sundaram et al. Liver Transplantation 2003;9:783
25. Etiology of Liver Disease Leading to Neonatal OLT Giant cell hepatitis most commonly reported indication for neonatal OLT
Accounts for >1/2 OLT in age group
Includes intrauterine & postnatal infections & inborn errors of metabolism
Most cases of giant cell hepatitis: no discernible etiology
Cholestatis w/o abrupt liver failure
Patients can endure wait for donor allograft
26. Etiology of Liver Disease Leading to Neonatal OLT Neonatal hemochromatosis: most frequent cause of acute liver failure in neonate
Life expectancy measured in days
Other reasons for neonatal OLT:
Hepatitis B
Enteroviral & echoviral hepatitis
TPN-associated liver disease
Hepatic hemangioendotheliomatosis
27. Neonatal OLT: Recipient Status Tenuous medical condition:
High waiting list mortality
Poorer post-transplantation survival
Most are UNOS I
Respiratory function compromised
Often already intubated at time of OLT
>50% have ascites impairing ventilation
Depressed cardiac function (cause?)
Inordinate number have cardiac arrest during OLT
28. Neonatal OLT: Recipient Status Renal insufficiency
Intrinsic immaturity of neonatal kidney
Effects of liver failure on renal function
Many on hemodialysis or CVVH(D)
Malnutrition a significant problem
Many liver diseases begin in utero: LBW
Normal body mass accrual poor despite aggressive enteral or parenteral hyperalimentation
29. Neonatal OLT: Recipient Status Malnutrition:
Neuroimaging shows brain atrophy in most
Malnutrition contributes to increased susceptibility to serious bacterial infections pre- and post-OLT
Typical complications of acute liver failure also seen:
Encephalopathy: subtle in presentation
Cerebral edema but w/o herniation (pliable cranium)
30. Neonatal OLT: Recipient Status Complications of liver failure:
Neurocognitive deficits nearly uniform in survivors of neonatal OLT
Particularly severe in those with metabolic conditions w/ hyperammonemia
Bleeding complications frequent:
GI bleeding
Intracranial hemorrhage more common as expected in newborns
31. Neonatal OLT: Donor Considerations Extremely limited donor organs
Full-sized allografts from newborns rarely available; such grafts often ineffective
Full-sized grafts from donors <6 kg (regardless of age) associated w/ high rates graft failure
Technical variant grafts (CAD or LR) the norm for neonatal OLT
ABO-incomptible allografts: neonates lack prior sensitization to antigens; no decrease in graft survival with incompatible grafts at 1 or 5 years
(Cacciarelli et al. Transplantation 1997; 64:242)
32. Neonatal OLT: Donor Considerations Restricted abdominal size: left-lateral segment (segments II &III) allografts preferred
Monosegment transplantation an alternative method to expand donor pool
Over-sized allografts: delayed abdominal closure & prolonged ventilator dependence
33. Problem of Over-sized Graft Increased intra-abdominal pressure
Impairment of respiratory function
Decreased graft perfusion
Avoid with:
Skin closure over an open fascia
Use of a synthetic patch or silastic pouch
>1/2 early re-operations in neonatal OLT patients are for 2o abdominal closure
34. Problem of Over-sized Graft Oversized graft often triggers series of events that lead to graft failure & patient mortality
Prolonged ventilatory support may occur as a result of respiratory compromise with large graft
35. Operative & Postoperative Considerations in Neonatal OLT OLT in small, very sick neonate challenging; identified & unidentified reasons conspire to make it difficult!!
There is an increased frequency of re-operations
Problems due to technical variant grafts:
Longer periods of cold ischemia
Higher risk of primary non-function & poor early function
Increased risk of post-op bleeding & bile leak
Incidence of vascular thrombosis seems very high in neonatal OLT
36. Neonatal Post-OLT Considerations Vascular thrombosis likely a result of
Technical difficulties
Medical/physiologic idiosyncrasies such as relatively low perfusion pressures
Patients with vascular thrombosis have 1-year survivals of 50% vs 85% in those without thrombosis
Portal vein thrombosis less life threatening than HAT; often can treat conservatively w/o surgical revision
37. Neonatal Vascular Considerations Recovery from HAT is unusual in infant OLT
Thrombectomy rarely successful (15%)
Only 25% patients with HAT survive w/o retransplantation
Mortality reaches 50% in infants who undergo retransplantation for this indication
38. Neonatal Post-OLT Considerations Reoperations in unstable neonates may precipitate serious medical complications e.g., renal failure
Early reoperations:
Intra-abdominal bleeding
Biliary complications (1/3 patients)
Increased with technical variant grafts
Bowel perforations
Need for bowel resection
Treatment of diaphragmatic paralysis
39. Neonatal Post-OLT Considerations Immunologic immaturity: more infections, but fewer rejections???
Bacterial & fungal infections affect up to 75% patients, may result in up to 50% of deaths (Caciarelli; Beath et al. BMJ 1993;307:825)
EBV & CMV more likely to cause severe infection in these naïve patients
Neonates at greater risk for EBV-associated PTLD due to lack of prior EBV infection/exposure
40. Summary: OLT in Small Patients Small, young patients provide numerous challenges following OLT
Survival appears to continue to improve
Team effort essential with participation of surgeon, intensivist, gastroenterologists, nurses & many others to ensure success
Anticipation of problems & prompt intervention important!
41. To receive email copy of this presentation contact me at jbrill@mednet.ucla.edu
Thanks to Michael Ament for all of his help with this presentation!