Intraoperative assessment of liver transplantation with marginal liver grafts

Intraoperative Assessment of Liver Transplantation With Marginal Liver Grafts J. Bricen˜o, C. Pera-Rojas, M. Lluch, J. Padillo, G. Solorzano, and C. Pera-Madrazo

T

HE USE OF marginal liver donors is justified because of the donor organ shortage and the terrible scenario of deaths while on waiting lists. The limitation of the cadaveric donor pool has necessitated a reevaluation of liver donor criteria to include grafts that were previously considered high risk. However, these organ are inferior, one way or another, and the clinical outcome of the transplant is more likely to be poor. In large series of liver transplantation (LT), recipient survival seems not to be affected with the use of marginal liver grafts. Conversely, long-term graft outcome,1 delayed nonfunction and need for early retransplantation,2,3 and initial poor function4 are seriously impaired. Another concern is relative to the impact that reperfusion of these marginal livers may have on the anesthetic management of the recipient. The aim of this study was to assess the effect of high-risk livers on metabolic, renal, hemodynamic, and respiratory parameters at the neohepatic phase of the recipient procedure. METHODS The most recent of 325 consecutive LT were reviewed retrospectively. Marginal liver donor criteria in this series included3: older than 60 years (n ⫽ 42), an ICU stay with ventilatory support ⬎4 days (n ⫽ 41), an ischemia time ⬎ 13 hours (n ⫽ 37), a high inotropic drug use (dopamine doses ⬎ 10 ␮g/kg per minute, or any doses of other amines) (n ⫽ 44), prolonged hypotensive episodes ⬎ 1 hour ⬍60 mm Hg (n ⫽ 23), a peak serum sodium ⬎ 155 mEq/L (n ⫽ 42), and high levels of bilirubin (⬎2.0 mg/dL), SGOT (⬎170 U/L), or SGPT (⬎140 U/L) (n ⫽ 51). A total of 46 variables between metabolic, renal, cardiovascular, and respiratory were recorded in each recipient at the end of the dissection phase (phase I), at the beginning of the anhepatic phase (phase II), and 5 minutes after liver reperfusion (phase III, or postreperfusion phase). Monitored variables included heart rate (HR, beats/min), mean artery pressure (MAP, mm Hg), mean pulmonary artery pressure (MPAP, mm Hg), pulmonary artery wedge pressure (PAWP, mm Hg), central venous pressure (CVP, mm Hg), cardiac index (CI, L/min/m2), systemic and pulmonary vascular resistance indices (SVRI and PVRI, dynes s/cm5/m2), left stroke work (LSW, gm-m/ beat) and LSW index (LSWI, gm-m/m2/beat), right stroke work (RSW, gm-m/beat) and RSW index (RSWI, gm-m/m2/beat), end systolic volume (ESV, mL/m2), urine output (UO, mL/h), inspired oxygen fraction (FIO2), partial pressure of arterial oxygen (PaO2, mm Hg), partial pressure of arterial CO2 (PaCO2, mm Hg), A-V oxygen content difference (A-V DO2, mL/dL), arterial oxygen content (CaO2, mL/dL), oxygen delivery index (DO2i, mL/min/m2), © 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

and oxygen consumption index (VO2i, mL/min/m2). Postreperfusion syndrome (PRS) was defined as a decrease in MAP of at least 30% from baseline for at least 1 minute within 5 minutes of reperfusion.5 Recipient subgroups relative to donor characteristics were well matched for age, gender, primary diagnosis, UNOS status, Child-Pugh score, number of recipients with venovenous bypass, clamping of cava vein without venovenous bypass or unclamping cava vein with piggyback technique, and preoperative biochemical and metabolic parameters. Analysis of variance for sequential measurements and General Lineal Model of ANOVA for comparison of donor subgroups were used to determine significance. Results were expressed as mean ⫾ SD.

RESULTS

LT with older donors and donors with a prolonged ischemia time, a prolonged ICU stay, or with hypotensive episodes did not differ with respect to those LT with good livers when compared at the postreperfusion phase. Metabolic, hemodynamic, and respiratory profiles at the neohepatic phase of LT with livers from donors with high inotropic drug use and hypernatremic donors were similar to those LT with good livers. However, the use of these subgroups of marginal livers was accompanied by an increase in renal impairment after reperfusion. A decrease in urine output and increase in seric creatinine and urea were common events at the postreperfusion phase with these livers. Needs of furosemide (P ⫽ .003) and manitol (P ⫽ .05) were increased at this phase (see Table 1). Metabolic and renal observations at the postreperfusion phase of LT with livers from donors with high levels of bilirubin, SGOT, or SGPT were similar to those registered in LT with good livers. Cardiovascular and respiratory profiles were seriously affected with the employment of this donor subgroup. After reperfusion, a right and left ventricular dysfunction was commonly observed. Decreases in CI, ESV, LSW, RSW, and RSWI and increases in CVP and PAWP with a normal MAP from baseline defined a hemodynamic profile of a lesser rate of venous return, a volume unloading of the heart, and myocardial dysfunction with these From the Unit of Liver Transplantation (J.B., J.P., G.S., C.P.-M.) and Unit of Anesthesiology (C.P.-R., M.L.), Hospital Reina Sofia, Co´rdoba, Spain. Address reprint requests to Javier Bricen˜o, Department of Surgery (6th floor), Hospital Reina Sofia, Avda Mene´ndez Pidal s/n, 14004 Co´rdoba, Spain. 0041-1345/01/$–see front matter PII S0041-1345(00)02370-8 903

Transplantation Proceedings, 33, 903–905 (2001)

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BRICEN˜O, PERA-JOJAS, LLUCH ET AL

Table 1. Significant Renal, Cardiovascular, and Respiratory Observations With Livers From Donors With High Inotropic Drug Use, Hypernatremic Donors, and Donors with Increased Levels of Bilirubin, SGOT, and SGPT. Phase I

Unstable Donors Urine output Urea Creatinine Donors ⬎155 mEq/L Urine output Urea Creatinine Cholestatic donors CI CVP PAWP LSW RSW RSWI ESV A-V DO2 CaO2 DO2i PaO2 VO2i

Phase II

Phase III

Good Donors

Unstable Donors

Good Donors

Unstable Donors

Good Donors

Unstable Donors

P

325.9 ⫾ 230.8 52.7 ⫾ 61.9 1.2 ⫾ 1.2

329.4 ⫾ 341.6 48.5 ⫾ 42.1 1.3 ⫾ 1.2

83.0 ⫾ 79.1 45.4 ⫾ 38.9 1.2 ⫾ 1.1

86.4 ⫾ 78.2 45.6 ⫾ 41.8 1.3 ⫾ 1.1

307.0 ⫾ 339.3 41.2 ⫾ 29.5 1.4 ⫾ 1.0

.04 .002 .005

327.0 ⫾ 223.3 75.5 ⫾ 37.6 1.4 ⫾ 1.3

125.2 ⫾ 31.1 120.2 ⫾ 72.0 9.4 ⫾ 2.9 ⬎155 mEq/L 142.3 ⫾ 45.2 112.2 ⫾ 75.0 6.3 ⫾ 1.2

305.9 ⫾ 221.2 63.6 ⫾ 46.2 1.1 ⫾ 1.0

309.4 ⫾ 311.5 57.7 ⫾ 32.6 1.2 ⫾ 1.2

87.3 ⫾ 38.1 45.5 ⫾ 29.9 1.4 ⫾ 1.0

84.4 ⫾ 24.2 53.6 ⫾ 22.8 1.3 ⫾ 1.2

.05 .04 .02

5.7 ⫾ 1.7 11.7 ⫾ 5.4 14.2 ⫾ 5.8 93.2 ⫾ 33.9 13.0 ⫾ 7.0 7.5 ⫾ 3.9 99.1 ⫾ 32.4 1.8 ⫾ 1.0 12.6 ⫾ 6.1 841.7 ⫾ 287.9 202.5 ⫾ 76.2 145.3 ⫾ 38.8

6.4 ⫾ 2.0 9.6 ⫾ 4.6 13.0 ⫾ 5.2 105.6 ⫾ 29.5 15.1 ⫾ 7.5 9.8 ⫾ 4.4 116.2 ⫾ 32.7 2.4 ⫾ 0.9 15.6 ⫾ 2.4 967.6 ⫾ 282.2 211.0 ⫾ 79.7 140.1 ⫾ 55.4

4.2 ⫾ 1.7 11.3 ⫾ 5.8 11.8 ⫾ 5.4 66.8 ⫾ 32.9 8.4 ⫾ 9.4 4.8 ⫾ 5.3 70.5 ⫾ 30.6 2.4 ⫾ 1.9 13.5 ⫾ 5.9 649.8 ⫾ 299.0 221.6 ⫾ 75.1 103.6 ⫾ 40.8

4.8 ⫾ 2.1 10.6 ⫾ 5.4 10.0 ⫾ 5.1 69.4 ⫾ 38.9 10.1 ⫾ 7.6 5.5 ⫾ 4.0 84.3 ⫾ 42.2 2.8 ⫾ 1.1 15.9 ⫾ 2.7 748.4 ⫾ 386.4 234.8 ⫾ 80.4 113.4 ⫾ 40.6

6.0 ⫾ 1.9 10.6 ⫾ 4.9 10.5 ⫾ 4.8 99.5 ⫾ 40.1 16.7 ⫾ 8.5 8.3 ⫾ 3.9 106.6 ⫾ 34.7 2.2 ⫾ 1.3 16.0 ⫾ 5.3 867.5 ⫾ 349.5 234.35 ⫾ 86.9 144.5 ⫾ 51.1

3.8 ⫾ 4.2 13.0 ⫾ 4.8 14.2 ⫾ 5.2 86.6 ⫾ 31.8 11.5 ⫾ 7.1 5.2 ⫾ 4.3 75.2 ⫾ 40.4 1.5 ⫾ 0.8 10.2 ⫾ 2.8 670.2 ⫾ 222.1 140.1 ⫾ 7.3 173.7 ⫾ 74.1

.009 .001 .012 .005 .004 .014 .002 .022 .001 .05 .013 .004

CI, cardiac index; CVP, central venous pressure; PAWP, pulmonary artery wedge pressure; LSW, left stroke work; RSW, right stroke work; RSWI, right stroke work index; ESV, end-systolic volume; A-V DO2, A-V oxygen content difference; CaO2, arterial oxygen content; DO2i, oxygen delivery index; PaO2, partial pressure of arterial oxygen; VO2i, oxygen consumption index. Results are mean ⫾ SD.

livers. With respect to respiratory variables, we obtained a pattern of pulmonary and systemic respiratory dysfunction with increases in A-V DO2 and VO2i and decreases in PaO2, CaO2, and DO2i. This profile reflects a pattern of poor oxygenated tissues, with a blockade in oxygen uptake and an impairment in alveolar exchanges (Table 1). DISCUSSION

A planned strategy to utilize marginal livers for transplantation may resolve three aspects: (1) securing of adequate recipient and graft survivals and an acceptable postoperative graft function, (2) the definition of a policy for allocation and priorization with these livers,6 and (3) the assessment of intraoperative profiles after reperfusion of high-risk graft and its impact on anesthetic treatment. This last problem has been poorly documented. The main result of the present study is that most of the livers considered as marginal did not affect postreperfusion phase, except in three cases: inotropic-dependent, hypernatremic, and cholestatic donors. Patients undergoing LT may develop significant hemodynamic instability, especially during the anhepatic stage, immediately after reperfusion of the grafted liver, and subsequently for 1 hour after reperfusion. Systemic hypotension on graft reperfusion, called postreperfusion syndrome, occurred in about 30% of a series of patients undergoing LT. This syndrome is a combination of hypotension, bradycardia, systemic vasodilatation, increase in cardiac filling pressure, and myocardial dysfunction.7 However, cardiac function is preserved immediately after graft

reperfusion and is very short lived.8 Moreover, right ventricular function was unaltered otherwise during uncomplicated LT, indicating that this procedure per se is not associated with significant right ventricular dysfunction. Hemodynamic phenomenology after reperfusion of livers from cholestatic donors seems to be different than observed in PRS. MAP was otherwise unaltered, and myocardial depression was profound but short lived. This significant ventricular dysfunction affected both right and left ventricles. Together with these hemodynamic changes, respiratory capability was also impaired, probably as a consequence of right ventricular failure. We may speculate about the presence of myocardial depressant factors with short lives that may be released from marginal grafts after reperfusion and not because of endotoxemia or absence of hepatic clearance of humoral factors during the anhepatic stage. In any case, these are temporary changes that did not compromise a successful LT. In conclusion, LT with livers from unstable, hypernatremic, and cholestatic donors need especial anesthetic attention during postreperfusion phase. REFERENCES 1. Hoffnagle JH, Lombardero M, Zetterman RK, et al: Hepatology 24:89, 1996 2. Yersiz H, Shaked A, Olthoff K, et al: Transplantation 60:790, 1995 3. Bricen ˜o J, Solo ´rzano G, Pera C: Tranplant Int 13(Suppl 1):249, 2000 4. Ploeg RJ, D’Alessandro AM, Knechtle SJ, et al: Transplantation 55:807, 1993

POSTREPERFUSION AND MARGINAL LIVERS 5. Aggarwal S, Kang Y, Freeman JA, et al: Transplant Proc 19:54, 1987 6. Bricen ˜o J, Pera-Rojas C, Solo ´rzano G, et al: Transplant Proc 31:440, 1999

905 7. Ellis JE, Lichtor L, Feinstein SB, et al: Anesth Analg 68:777, 1989 8. De Wolf AM, Begliomini B, Gasior TA, et al: Anesth Analg 76:562, 1993