Perioperative Challenges of the Small Liver Transplant Recipient

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Perioperative Challenges of the Small Liver Transplant Recipient

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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 of Neonates (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 [email protected] Thanks to Michael Ament for all of his help with this presentation!

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