Anaesthetic Protocol For Living Related Liver Tranplants (Recipient)
Dr. D. R. Porter
April 1995

1. Organisation
1. Referring Physician/Co-ordinator
2. Anaesthetist
3. Pre-operative Assessment
4. Patient Preparation
2. Theatre Set-Up
1. Equipment
2. Monitoring
3. Sampling
3. Anaesthetic Technique
1. Premedication
2. Preinduction
3. Induction
4. Maintenance
5. Surgery
6. Anhepatic Phase
7. Reperfusion/Neohepatic Phase
4. Postoperative Management
5. Tables

Intraoperative Investigations
Bottles Needed
Forms Needed
Drug Doses
Infusions
Target Investigation Values
O2 Flows for Various FIO2's at TFGF of 6 l/min

1. Organisation
1. Referring Physician/Co-ordinator
1. Inform Anaesthetists
2. Book theatres and inform Sister of patient's antigen/antibody status
3. Contact anaesthetic technician for theatre set-up
4. Order
1. Blood/red cell conc (rcc/pc) 4-6 units
2. 5 % albumin (HAS) 4 x 500 ml
3. Fresh Frozen Plasma (FFP) 4 bags
4. Platelets as indicated by pre-op count and risk category
5. Alert lab for per-op FBC's, coagulation screen, etc.
6. Alert anaesthetic technician for ABG's, electrolytes
2. Anaesthetist
1. Assess patient, if not already seen, and organise pre-op preparation.
2. Discuss theatre set-up requirements with technician, esp. if non-standard, e.g. fulminants or re-transplants.
3. Pre-operative Assessment
1. General
1. Previous GA's, previous abdominal surgery (adhesions = bleeding)
2. Portal hypertension (collaterals = more bleeding)
3. Previous shunts
4. Ascites
2. Respiratory system
1. ABG's
2. Hepato-pulmonary syndrome
3. Chest X-ray. ? effusion
4. Allergies and asthma
3. CVS
1. ? hyperdynamic circulation
2. Pulm hypertension ? need for PA catheter pre-op
3. Venous access
4. ? Special Ix e.g.
1. Echocardiogram
2. Right heart catheter to assess pulmonary hypertension
4. CNS
1. Level of consciousness
2. Pupils
3. Seizures
4. ICP (fulminant hepatic failure)
5. Metabolic
1. Na⁺, K⁺, renal fn (renal dysfunction is common), diabetes
2. Ascites, albumin, LFT's. Malnutrition is common.
3. pH, HCO₃^-
6. Microbiological

Any infection should be considered a contraindication to transplantation.
1. Temperature, wbc, ? persisting sepsis, ? recent pos. cultures or SBP (spontaneous bacterial peritonitis which is usually associated with ascites)
2. Viral antigen status (Hepatitis A, B and C, HIV, and CMV must be negative).
7. Haematology
1. Hb, Hct. Anaemia may be due to poor nutrition and bleeding varices. ? Upper GI endoscopy and injection of bleeding varices before transplantation.
2. Platelets
3. INR/PTR. Correct with vitamin K, clotting factor replacement or exchange transfusion.
4. Screen for hepatitis
4. Patient Preparation
1. Blood samples for FBC, LFT's, coagulation, leaving peripheral IV cannula in-situ for anaesthetic induction.

CXR.
2. Oral intake restricted to clear fluids in the period from 8 to 2 hours pre-op
3. Premed
1. Elixir temazepam 0.5 - 1.0 mg/kg
Atropine 10 - 20 ug/kg
1.5 h pre-op, orally
2. EMLA cream if no IV in-situ
3. In adults, use IV midazolam for premed
2. Theatre Set-Up
1. Equipment
1. Cannulae
1. Arterial: 20/22 G cannula
2. Peripheral veins: 16/18 G cannula connecting to single giving set through a warming coil for maintenance crystalloid (5-10 % dextrose)
3. Central veins (RIJV):
1. Triple lumen catheter (Vygon Multicath 1210.25 (14/18/18 G 10 cm)) for drugs, CVP and blood transfusion through warming coil (14 G channel) via 3-way taps or ramp
2. Swan introducer may be needed for blood transfusion in older children or for PA catheter if cardiac problems indicate (Paediatric Swan Ganz thermodilution catheter)
2. Anaesthetic circuit
1. ET tube: Nasal uncuffed with Tunstall connectors for fixation to forehead (convenient for post-op ventilation)
2. Heated humidifier
3. Nasogastric tube
1. Intra-op to reduce gastric distension
2. Post-op use
4. Urinary catheter with Urimeter under head of table
5. Temperature
1. Rectal/Nasopharyngeal probe
2. Warming blanket, gamgee, plastic bag for limbs, space blanket
6. Drugs
1. Thiopentone, sux (+-), atropine, fentanyl, pancuronium
2. CaCl₂ 1 mmol/ml, KCl, NaHCO₃, Adrenaline (1:10,000), ephedrine
3. Infusions via syringe drivers
1. Atracurium 10 mg/ml x 20 ml (undiluted)
2. Dopamine (Body wt in kg x 3) mg in 50 ml to run at 2 ug.kg^-1.min^-1
3. Fentanyl 20 ml undiluted at 5-10 ug.kg^-1.h^-1
4. Mannitol 20 %, Dextrose 10 %
5. Antibiotics
6. Methyl prednisolone 500 mg amp.
7. Azathiaprine 50 mg amp.
2. Monitoring
1. ECG
2. 3 pressure transducers (arterial, CVP, and Swan Ganz in older/bigger children who are ill). Heparin is not used as the small amounts of heparin may not be metabolised by the liver causing abnormalities in coagulation.

Thermodilution cardiac output may be needed in some patients.
3. Core temp. (naso-pharyngeal, oesophageal or rectal)
4. Capnograph. An increase in ETCO2 at reperfusion is indicative of ongoing cellular metabolism
3. Sampling
1. Prepare syringes, bottles and forms (6 each) for:-
1. ABG's
2. Na⁺, K⁺, Ca²⁺, glucose (glucometer may be adequate)
3. Hb/Hct, platelets, coagulation (TEG, INR, fibrinogen/FDP)
2. Inform haematologist about likely samples (hourly and half hourly in anhepatic phase).
3. Anaesthetic Technique
1. Premedication: IV midazolam on collection of patient if IV in-situ and oral premedication insufficient.
   (Oral midazolam 0.5-0.75 mg/kg or IV midazolam 0.025-0.1 mg/kg [1])
2. Preinduction
1. NIBP, oximeter, ECG
2. Give antibiotics. Currently,
1. Ceftazidime 20 mg/kg, and
2. Augmentin 30 mg/kg.
3. Induction

Check on arrival time of surgical team before proceeding!
1. Pre-oxygenation
2. Thiopentone, fentanyl
3. Suxamethonium (+-), Pancuronium, ETT (Nasal intubation is preferred in the absence of a severe coagulopathy), N/G
   Hammer recommends an oral cuffed tube [1].
4. Temp probe
5. Venous lines
1. Peripheral - largest feasible
2. Jugular - Triple lumen, 4-5 FG for rapid transfusion in patients over 20 kg or high risk
6. Start infusions: Dopamine, atracurium, fentanyl multiplexed on one channel of the triple lumen catheter. (Dr. Radha -> Start infusion of CaCl₂ 10 % at 0.5 ml/h and vary according to Ca²⁺.)
7. Blood for ABG's, electrolytes, FBC and TEG
4. Maintenance: Air:O₂:Isoflurane, start with FIO₂ 50 %. Nitrous oxide is avoided because of the potential for distension of the bowels during the long surgical procedure.
   The operating theatre may be warmed to 21-26 °C (72-62 °F) in order to prevent hypothermia during anaesthetic induction and vascular catheterization [1].
5. Surgery
1. Antibiotics if not already given. Hammer recommends IV ampicillin 50 mg/kg and ceftriaxone 50-75 mg/kg [1].
2. Give FFP & platelets (if < 50 000) if and only if indicated by pre-op coagulation status and first TEG. Particularly important in post-KASAI patients. Should preferably be given early.
3. Give mannitol if urine flow < 0.5 ml.kg^-1.h^-1
4. Give 5 % dextrose at 5 ml.kg^-1.h^-1 approx., or as required to prevent too great changes in Na⁺. Na⁺ load is determined largely by requirement for blood and blood products. (Dr. Radha -> To add MgSO₄ 10 mmol to each 500 ml maintenance fluid)
5. Replace blood loss with whole blood/red cell conc, human albumin 5 % (HAS) to maintain MAP, CVP/PAWP, cardiac output and haematocrit (at about 30 %)
6. Hourly estimations of ABG's, Na⁺, K⁺, Ca²⁺, glucose, H+, Hb (keep at about 10 g/dl), platelets, INR. Maintain paCO₂ 35-40, pO₂ >120, pH 7.35-7.45, PCV 28-32.
7. Veno-Venous bypass is rarely required in children, who usually tolerate caval & portal clamping with the aid of volume loading.
6. Anhepatic Phase
1. Give steroids (Methylprednisolone: adults 10 mg/kg and children 15 mg/kg)
2. Repeat antibiotics
3. Continue drug infusions
4. Monitor 1/2 hourly,
1. Glucose: During the anhepatic phase, no endogenous glucose is released. Therefore, a dextrose (5 %) drip is essential
2. Ca²⁺: Control to 1.0-1.2 mmol/l. Give incremental doses of CaCl2 10-20 mg/kg [1].
3. If K+ > 5.0, in spite of an alkaline pH, 0.25-0.5 g/kg of glucose followed by IV soluble insulin 0.2 u/kg may be given [1].
4. ABG: Prevent or partially correct any severe acidosis (BE < -15)
5. CVS

Without VVBP cardiac output usually falls to about 50% of pre-clamp values, so modest volume load may be needed, but excessive volume loading in this phase may precipitate pulmonary oedema on release of the caval clamps. Probably best to maintain CVP/PAWP at just below the pre-clamp values if BP is stable.
Inotropes or vasoconstrictors may be necessary if MAP does not recover spontaneously within 10-15 min.
7. Reperfusion/Neohepatic Phase
1. Thorough irrigation of the graft to flush out preservation fluid is important in minimising the reperfusion syndrome.
2. Have Ca²⁺ (CaCl₂) ready for reperfusion, to counter acute hyperkalaemia.
Anticipate fall in pH with reperfusion. HCO₃^- is rarely needed and only if BE < -15.
3. Expect sharp rise in CVP with arterial hypotension & bradycardia on release of IVC clamps (increased venous return and myocardial depression) if bypass has not been used. Adrenaline may be required, but hypotension and bradycardia are usually transient, sometimes with T wave changes and pulmonary hypertension.
4. Major blood loss from anastomoses may require re-clamping, as well as rapid transfusion. (Dr. Radha -> Trasylol should be avoided to avoid the possibility of micro-emboli formation in the microcirculation especially in the liver of paediatric patients in the reperfusion phase where there is increased thrombosis.)
5. Later as graft recovers, K+ may fall sufficiently to require replacement, so increase frequency of estimations.
6. Acidosis will tend to correct spontaneously if new liver is functioning, so be sparing with HCO3-.
7. Give FFP, platelets & cryoprecipitate as indicated by INR and TEG, avoiding over correction. The TEG is usually done about 30 min after reperfusion as the coagulation defects immediately post-reperfusion are found to correct themselves partially. Maintain the INR at 1.5-2.0 and definitely < 2.5.
8. The dose of Transamin (Tranexamic acid) is 10-15 mg.kg^-1
9. Adjust Hct to 28-32 %.
10. Because hyperglycaemia following reperfusion is common, dextrose-free IV solutions should be administered unless the serum glucose < 5.5 mmol/l [1].
    Soluble insulin may be given according to the glucometer readings

Glucometer	Dose
10-15 mmol.l-1	2 u.h-1
>15 mmol.l-1	4 u.h-1

    
4. Postoperative Management
1. Controlled ventilation with moderate PEEP (2-5) for 12-24 h. Relaxants are not usually required, except in fulminants at risk of raised ICP, if analgesia and sedation are adequate.
2. Analgesia with continuous infusion of morphine

40 ug.kg^-1.h^-1, supplemented by small bolus doses prn., rather than higher infusion rates.
Lower infusion rates if coma preceded surgery or renal function poor.

3. Sedation with midazolam infusion 100 ug.kg^-1.h^-1, aiming for light sedation and a patient accessible to verbal stimulus.
4. Clear fluids as 5 % dextrose IV 4 ml.kg^-1.h^-1
5. Insulin infusion by sliding scale.
6. Dopamine infusion at 2 ug.kg^-1.min^-1
7. Keep MAP 60-80 for infants and small children, or 70-90 for older children and adolescents [1].
8. Fluids
1. Volume replacement with blood/RCC, FFP, HAS (albumin) to maintain optimum CVP, PAWP, cardiac output and Hct. FFP should be used cautiously as it can lead to increase in thrombosis post-op esp in smaller children. Generally keep INR < 3.0, although Dr. Tan KC doesn't mind going up to 6.0 so that he can use it as a guide to liver function.
2. Colloid requirements are often considerable and in excess of drainage losses. These drainage losses together with the accumulation of ascitic fluids can cause haemoconcentration. It is therefore, better to use colloids rather than blood.
3. Oliguria is common. The urge to give frusemide should be resisted, esp in the presence of aminoglycoside antibiotics, unless there is real evidence of fluid overload.
9. If there was difficulty in abdominal closure, or if there is any suspicion of continued intra-abdominal bleeding, the femoral-venous pressure gradient should be monitored. This gradient and the transfusion requirement to maintain PAWP & CVP are better guides to blood loss than drainage losses or girth measurements.
10. Nutritional support, enteral feeding or TPN, should be started as soon as haemodynamic stability allows.
11. Weaning from CMV to SIMV is usually possible by 12 h. Relaxants should be withdrawn before sedation/analgesia. Analgesic & sedative infusions should be stopped.
12. Immunosuppression: On day 1, Cy A and Azathiaprine are added to the steroids that were started in theatre, as soon as it is clear there is no renal impairment.
5. Tables

Bottles Needed	No.
K2 EDTA (Green cap)	10
Cit Na 0.105M (Vacutainer, Blue cap)	10
Plain bottle	10

Forms Needed	Tests to Order	No.
Haematology	Hb,Plat,PCV,INR	10
Chemistry	ABG,Na,K,Ca2+(ionised)	10

Target Investigation Values

Ix	Target	Units	Timing
Hct	0.28 - 0.32
Hb	9 - 11	g.dl-1
Ca2+	1.0 - 1.2	mmol.l-1
paCO2	35 - 40	mm.Hg
paO2	120	mm.Hg
pH	7.35 - 7.45
BE	> -15	mmol.l-1	An- & neo-hepatic phase
INR	1.5 - 2.0	Max 2.5	Neohepatic phase
	> 3.0	Max 6.0	Post-op
Urine	0.5	ml.kg-1.h-1

O₂ Flows for Various F_IO₂'s at TFGF of 6 l/min

References

1. Anaesthesia for liver transplantation in children by Gregory B. Hammer MD and Elliot J. Krane MD. Paediatric Anaesthesia 2001; 11: 3-18