Introduction OLT recipients who develop multiorgan dysfunction. (1) The

Introduction

Orthotopic
liver transplantation (OLT) is the only definitive therapy for the treatment of
end-stage liver disease. Although most recipients do well and are discharged
within 2 weeks of transplantation, some patients require prolonged
hospitalization, and this can dramatically increase both morbidity and the
costs associated with OLT. Previous studies have demonstrated that a prolonged
hospital stay following OLT most frequently occurs in patients without
immediate bile production, in patients who have received more than 20 U of
platelet transfusions during the transplant operation, in patients with poor
urine output during the immediate post-OLT period, and in OLT recipients who
develop multiorgan dysfunction. (1)

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The
occurrence of AKI in patients undergoing LT is associated with reduced patient
and graft survival not only in the perioperative period but also in the longer term
(2) with reports of 10% progressing to endstage renal failure. (3) AKI reduces
patient survival and leads to increased health care costs because of increased
intensive care and hospital stays (4)Furthermore, increasing evidence supports
the fact that even relatively minor deteriorations in renal function not
requiring RRT are associated with inferior patient and renal outcomes in the
longer term; this underlines the importance of the early identification of at risk
individuals and the need to identify preventative strategies. (5)These
consensus definitions of AKI in the LT population have been validated by
studies in which an increasing severity of renal dysfunction (RIFLE grades R-F
or AKIN stages 1-3) correlated with reduced patient survival. (6)

 

The aim of the present study is to assess
the influence of different perioperative factors associated with prolonged
length of ICU duration following living donor liver transplantation and to
evaluate the effect of duration of ICU to both short term and long term
complications following liver transplantation.

Methods

Study design:

 

 A cross-sectional (retrospective)
study was conducted on patients who underwent liver transplantation at El Manial
Cairo- University Hospital. Most of our patients had underwent living donor
transplantation due to end stage liver disease caused by chronic hepatitis C
(HCV) or HCV complicated by hepatocellular carcinoma. They were 44 males and 5
females, their age ranged from 20 to 59 years old with a mean of (48 ±7.51 SD).

Patients were divided into 2 groups according to the
duration of ICU stay:

Group A: Including patients who needed ICU stay for ? 7
days

Group B: Including patients who were in need for ICU stay
for <7 days.         The study protocol conformed to the ethical guidelines of 1975 the        Helinsici      declaration and was approved by the ethical committee of         internal medicine, faculty of medicine, Cairo University                Written informed consents were obtained from participants in this study          Methods:   The data base of Al Manial Hospital of liver transplantation was used to identify patients who underwent OLT between 2006 to 2012 All our patients were subjected to thorough history taking & complete physical examination, assessment of patients' perioperative factors like the need for mechanical ventilation, the need for inotropic support, follow up of vital signs and fluid balance of patients following transplantation as well as laboratory investigations including serum creatinine and BUN during ICU stay and following the morbidities and the mortality of patients through 3months and one year post transplantation. Statistical analysis: Data were coded and entered using the statistical package SPSS version 21. Data was summarized using mean, standard deviation, median minimum and maximum in quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Comparisons between quantitative variables were done using the non-parametric Mann-Whitney for comparing categorical data, Chi square (c2) test was performed. Exact test was used instead when the expected frequency is less than 5, P-values less than 0.05 were considered as statistically significant. Results:   Demographic and clinical data comparing pretransplant and post transplant variables between group (A) & group (B) are summarized in table (1)   The study revealed that there was no significant difference between both groups as regard blood urea nitrogen ( BUN )   (P value: 0.836) however serum creatinine in group A(1.32  ± 0.51 SD) was higher  than that of group B (1.2  ± 0.78 SD) which is statistically significant(P value 0.039) and this is shown in figure (1)&(2). Systolic blood pressure ( SBP)   was  (118.96  ± 14.67 SD) in patient of group A . While systolic blood pressure was (128  ± 18.14 SD) in patient of the group B. Diastolic blood pressure ( DBP) was  (67.29   ± 10.21 SD) in group A. While diastolic blood pressure (67.20  ± 8.3 SD) in patient of the group B. The study revealed no significant difference between both groups regarding central venous pressure measurement(8.17  ± 2.85 SD in group A vs 8.04   ± 2.28  SD in group B )  as well as blood pressure measurement ;systolic blood pressure ( SBP)   was  (118.96  ± 14.67 SD) in group A vs (128  ± 18.14 SD) in group B and diastolic blood pressure ( DBP) was  (67.29   ± 10.21 SD) in group A  compared to group B  (67.20  ± 8.3 SD). P value :(0.864, 0.119 and 0.976) respectively       It was noticed that use of Mycophenolate Mofitil , as part of combined immunosuppressive drug therapy , following liver transplantation was higher among patients of the second group who needed shorter duration of ICU  stay ( 96 percent compared to 75 percent at the first group ) . Hence, there was significance difference between the use of Mycophenolate Mofitil , as part of combined immunosuppressive drug therapy, between the two groups of study ( p value = 0.049 ) . Discussion: Many studies have analyzed factors related to patient and graft survival following OLT.(7).  These factors including patient age, BMI and co- morbidities as well as ICU stay. The early post-operative period is a crucial time when intensive care management of liver transplanted patients mainly focused on rapid hemodynamic stabilization, correction of coagulopathy, early weaning from mechanical ventilation, proper fluid administration, kidney function preservation, graft rejection prevention, and infection prophylaxis (8).   In a state-of-the-art review published in 1994, the authors reported an expectation of 36 hours of postoperative mechanical ventilation and an average 6-day ICU stay for routine cases. (9).  Depending on these findings, we hypothesized that the duration of post transplantation ICU admission may have an impact on transplantation outcome on patient with HCV.  The aim of the study was to determine the factors associated with prolonged length of ICU admission, and the impact of this duration  on both short-term and long-term graft and hence  patient survival. Our study revealed that high Child –pugh score has an impact on prolongation of ICU stay ( P value 0.042 ) .  In agreement with Chen P. et al.2014,  recipients with higher Child-Pugh scores have risk of serious complications during the first post-transplant year , shortened recipient survival and pro­longed primary hospitalization duration and postoperative ICU-stay(10). MELD was adopted by the United Network for Organ Sharing (UNOS) in 2002 for prioritization of patients awaiting liver transplantation in the United States. (11) (Freeman RB et al 2002 ). Interestingly, the MELD score was not found to be a risk factor in our study ( P-value:0.252) .This was in consistent with Cholongitas E et al 2006 and Moon JI et al 2010 who stated that it was demonstrated that it is not a predictor of survival in liver transplant recipients (12& 13), and this may be explained by that the components of MELD score not completely account for the expression of hepatic dysfunction in different chronic liver disease patients (14)      The occurrence of acute kidney injury in patients undergoing LT is associated with reduced patient and graft survival not only in the perioperative period but also in the longer term, with reports of 10% progressing to endstage renal failure. AKI reduces patient survival and leads to increased health care costs because of increased intensive care and hospital stays. Furthermore, increasing evidence supports the fact that even relatively minor deteriorations in renal function not requiring RRT are associated with inferior patient and renal outcomes in the longer term; this underlines the importance of the early identification of at risk individuals and the need to identify preventative strategies (15).        Posttransplantation assessment of kidney function of the two groups of patients revealed increased length of ICU duration among patients with higher creatinine level ( P value = 0.039 ) which was in agreement with Jenny O et al 2009 ( P value was 0.0001) that stated that renal insufficiency at the time of transplantation have been associated with a significant increase in graft loss and mortality in these patients(16).      Although creatinine is a relatively poor biomarker of renal function because changes in serum creatinine levels tend to lag behind dynamic changes in renal function ,however consensus definitions of AKI (RIFLE grades R-F or AKIN stages 1-3) still depend on serum creatinine or urine output as the novel biomarkers of AKI are less helpful.        Our study revealed no significant difference between both groups as regard rising of serum BUN which may be explained by exposure of both groups to the same factors which may elevate BUN rather than renal impairment as use of steroid, GIT hemorrhage and infections   Despite increased incidence of infection among patients with prolonged ICU stay, there was no statistical difference of incidence of infection on both groups (P value = 0.147). On the contrary to what noticed by Ghobrial RM et al 2001, who stated that post-transplant infections especially of bacterial causes (including pneumonia, bacteremia, or urinary tract infection) during the transplant hospitalization represents one of the most important factors independently associated with 1-year mortality in those patients with prolonged length of hospital stay particularly at  post transplantation ICU  period, but the p value at this study was < 0.0001(16).  Recently Cybele L & co studied 122 patients of total 223 developed an infection during the follow-up period (1-year cumulative event rate of 56%), with the majority (66%) of these occurring within 30 days after transplantation & declared that infections occur commonly after LDLT, with most infections occurring early and being related to the hepatobiliary system. Higher MELD scores, the type of biliary anastomosis, presence of biliary complications, and prior pretransplant infections are independently associated with a higher risk for infections (17) It may be accounted to the presence of independent pretransplant risk factors that increasing the risk of infection in both groups It was also noticed that the incidence of acute rejection was higher than chronic rejection among the patients of study of nearly equal occurrence between both groups due to small size sample.   Biliary complications were the most common surgical complication among the study group , occurring at 32 % of patients .It was noticed that patients of reduced duration of ICU stay, had lower incidence of biliary complications especially stricture  than those with prolonged length of ICU stay.  Choong Heon Ryu and Sung Koo Lee 2011 had reported the incidence of biliary stricture was 28% to 32% following living donor liver transplantations (18). Jenny O. Smith et al 2009 analyzed both pretransplant and posttransplant variables thought to affect the length of stay and demonstrated that biliary complications are one of the important factor affecting both duration of ICU stay and post transplant survival, occurring in 17.6% in patient with prolonged stay compared to 5.3%  in patient with lower duration with p value = < 0.001(15)       It was observed that post transplant mortality, either immediately or of 1 year incidence, was much lower at patient with short duration of ICU stay. Incidence was 45.8% among patients with prolonged post transplant ICU compared to 24.0% in the second group with p value = 0.108. This was in consistent with Shiffman ML et al  2006 who demonstrated that differences in pretransplant patients' condition made a difference in the prognosis after LT including poor ICU course and higher mortality (19). Finally, The potential influence of immunosuppressive drugs on the morbidity and mortality after LT deserves a detailed comment since these drugs may affect the longterm outcome after LT in different ways: by their effect on renal function, by their effect on glucose and fat metabolism, and by increasing the risk of malignancies (20) In a previous study; tacrolimus-based therapy was associated with a better overall survival compared with cyclosporine-based therapy was rationalized by the berelated  lower incidence of acute rejection found in patients treated with tacrolimus, and the consequence of its better profile on renal function, blood pressure, and serum lipid levels compared with clyclosporine.(21)  In the current study, different immunosuppressant regimens were also analyzed. among different immunosuppressant regimens, it was noticed that the use of mycophenolate mofitil as a part of combined immunosuppressive therapy was associated with reduced ICU  duration post liver transplantation and reduced incidence of graft rejection ( it was used for 18 patients of first group with prolonged length of ICU stay compared to 24 patients at the second group with p value = 0.049). This matches with what was mentioned by Wiesner RH et al 2005 who stated that recipients treated with MMF, tacrolimus, and corticosteroids had significantly increased patient survival (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P < 0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as compared to recipients treated with tacrolimus and corticosteroids alone.       We should mention a limitation of the present study as regard the small sample size; the results of this study will need confirmation in a larger patient population.      The study concluded that significant correlation between Child score of the patients of study and duration of ICU stay as well as outcome including both long term and short term survival following transplantation especially renal affection and the occurrence of acute kidney injury.