EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Length of stay is considered an important surrogate for transplant survival rate and resource utilization. Therefore, in the present study, our aim was to determine factors affecting length of hospital stay.

Materials and Methods: We retrospectively analyzed records of patients who underwent liver transplant at the Tehran University of Medical Sciences Liver Transplantation Center from March 2014 to March 2016.

Results: For our final analyses, there were 161 adult recipients, including 106 males (65.8%) and 55 females (34.1%). Univariate analyses showed that body mass index, Model for End-Stage Liver Disease score, duration of surgery, number of administered packed red blood cells and fibrinogen during surgery, reoperation, retransplant, bacterial infection, pleural effusion, ascites, renal failure that required dialysis, and wound infection were risk factors for length of hospital stay. After multivariate linear regression analysis, only body mass index (β = 0.016; P = .028), Model for End-Stage Liver Disease score (β = 0.017; P = .002), surgical duration (β = 0.002; P = .001), reoperation (β = 0.016; P < .001), presence of pleural effusion (β = 0.212; P = .042), and management of bacterial infection (β = 0.21; P = .03) and psychiatric problems after liver transplant (β = 0.213; P = .025) were independent risk factors for length of hospital stay.

Conclusions: The present study showed that multiple preoperative, intraoperative, and postoperative variables could have an impact on length of hospitalization. Therefore, methods for assessing these factors could improve patient outcomes and resource savings in liver transplant centers.

Key words : Hospitalization, Intensive care unit, Model for End-Stage Liver Disease

Currently, liver transplant (LT) is a widely accepted therapeutic modality for patients with end-stage liver failure.¹ Despite advances in medical and surgical techniques, postoperative complications are common and contribute to increased morbidity and mortality among LT recipients.^2,3 These complications can in turn lead to prolongation of hospital stays, subsequently resulting in financial burden for hospitals and psychologic impact on patients and their families.^4-6Moreover, due to limited resources and the substantially high economic cost of LT procedures, there can also be constraints imposed on transplant centers.7-9

Because of the complex nature of the LT process involving assessment of recipients and donors, it is difficult to accurately predict patient and graft survival.¹⁰ To date, a number of factors have been proposed that could affect postoperative outcomes of patients who undergo LT procedures, including preoperative status of the patient and graft condition, as well as the complexity of the surgical procedure.^1,11-15 Recently, increased attention has been given to the length of stay (LOS) in the hospital after the LT procedure; LOS has been used as an index for estimating both hospital expenditures and survival rates of patients.16-18 Studies have suggested that the severity of the underlying liver disease is significantly associated with longer duration of hospitalization and higher in-hospital mortality rate.^17,19,20 Understanding the factors that lead to a longer LOS could help physicians to mitigate the effects of these factors, thus allowing more effective resource allocation and decreased hospital costs.

Most LOS studies have focussed on associations between preoperative patient assessments and clinical outcomes. So far, limited data exist regarding the influence of transplant and posttransplant factors on hospital LOS. Therefore, in this study, our aim was to assess possible correlations to LOS with all factors in the preoperative, intraoperative, and postoperative LT periods.

Materials and Methods

Patients
In this cross-sectional study, we analyzed 194 medical records of patients who underwent LT at the Tehran University of Medical Sciences (Tehran, Iran) from March 2014 to March 2016. All patients were over 18 years of age and underwent deceased-donor LTs. Patients were excluded if they died during hospitalization, had a prior history of LT, and had multiple organ transplants. The hospital LOS was defined as both the transplant intensive care unit (ICU) and the transplant ward stay.

Data were collected from admission of patients to the wait list clinic and included the following variables: age, biological sex, body mass index (BMI), Model for End-Stage Liver Disease (MELD) score at transplant, history of associated illnesses, history of ascites, history of portal vein thrombosis, indication for LT, prior history of hepatocellular carcinoma, need for dialysis, history of renal failure, and history of abdominal surgery.

Intraoperative transplant variables included recipient age at the time of LT, donor biological sex, donor age, donor BMI, donor renal insufficiency, and donor’s previous history of surgery. Other variables assessed during transplant included warm and cold ischemic time, length of surgery, and transfusion requirements for packed red blood cells (RBCs), fresh frozen plasma, platelets, and fibrinogen. Postoperative variables included early allograft dysfunction, intra-abdominal hemorrhage, need for resurgery, liver artery and portal vein thrombosis, postoperative ascites, renal failure, pleural effusion, bacterial infection, wound infection, need for retransplant, and psychiatric problems.

Model for End-Stage Liver Disease score was calculated based on United Network for Organ Sharing adjustments.²¹ This study was approved by the local ethics committee of the Tehran University of Medical Science and conducted in accordance with the Declaration of Helsinki and other applicable guidelines, laws, and regulations.²²

Statistical analyses
Categorical variables are reported as percentages and were analyzed using the chi-square test. Continuous numeric variables are reported as mean ± standard deviation or median and 25th to 75th percentiles if nonnormally distributed. For independent numeric variables, the t test was used; independent nominal variables were used as indicated. Statistical significance was defined as P < .05. Pretransplant and posttransplant factors that could have an influence on LOS were analyzed. Stepwise linear regression analysis was conducted to evaluate both the donor’s and the recipient’s demographic and clinical variables on LOS. If factors achieved statistical significance (P < .05) in univariate analyses, they were then evaluated with multiple logistic regression analyses. All data were analyzed using SPSS version 18.0 software (SPSS Inc.; Chicago, IL, USA).

Recipient characteristics
Over the study period, our center performed 194 LT procedures. Of these patients, 33 cases were excluded due to exclusion criteria, as summarized in Figure 1. Of the 161 patients included in our final analyses, 106 (65.8%) were male patients. About half of patients had BMI between 18 and 25 kg/m². Male and female patients differed significantly based on distribution of BMI (P < .001). Most patients were older than 55 years of age. The most common underlying cause of cirrhosis was cryptogenic liver disease seen in 37 patients (23%), followed by hepatitis B virus (29 patients), autoimmune disease (27 patients), and hepatitis C virus (26 patients). A previous history of abdominal surgery was seen in 52 patients (32.3%). The pretransplant mean serum albumin level was 3.22 ± 0.63 mg/dL. Other demographic and clinical characteristics of LT recipients are summarized in Table 1.

Donor characteristics
Data on donor characteristics were available for 161 patients (Table 2). The mean age of donors was 37.37 ± 12.66 years, with most donors older than 45 years of age (32.9%). The most common cause of brain death was head trauma (44.1%) followed by cerebrovascular accident due to intracerebellar hemorrhage (27.3%), drug toxicity (11.2%), arteriovenous malformation (9.9%), and other causes (4.4%). Most donors (49.7%) had BMI less than 25 kg/m².

A previous history of surgery was seen in 51 patients (31.7%). Renal insufficiency (serum creatinine > 1.6 g/dL) was observed in 33 patients (20.5%).

Associations between preoperative variables and length of hospital stay
Male recipients had shorter hospital LOS (16.88 ± 9.52 days) than female patients (17.41 ± 8.6 days). However, this difference did not reach statistical significance (P = .486). Recipients who were less than 25 years of age had shorter hospital LOS (14.11 ± 3.44 days). A significant correlation existed between BMI (r = 0.257; P < .001) and MELD score (r = 0.274; P < .001) of recipients and their LOS (Table 3). Patients with higher BMI were more likely to experience prolonged LOS.

Associations between intraoperative variables and length of stay
The mean duration of surgery was 279.57 ± 52.21 minutes. There was a significant association between surgical duration and LOS (r = 0.281; P < .001). Transfusion requirements during LT were 1.8 ± 2.3 units of packed RBCs (median 1; range, 0-13), 0.1 ± 0.4 units of fresh frozen plasma (median 0; range, 0-4), 0.4 ± 0.2 units of platelets (median 0; range, 0-2), and fibrinogen 1.96 ± 1.98 g (median 2; range, 0-9). Likewise, patients who received packed RBC transfusion had 2.3 times greater likelihood of postoperative LOS ≥ 11 days (odds ratio = 2.5; 95% confidence interval, 1.5-4.1; P < .01). Moreover, the number of packed RBCs used (r = 0.194; P = .013) and the number of injected fibrinogen (r = 0.189; P = .016) had a significant correlation with LOS after LT. On the other hand, no correlation was observed between warm and cold ischemia time and LOS (P > .05) (Table 3).

Associations between postoperative variables and length of stay
The mean hospital and ICU LOS of the study population was 17.07 ± 9.19 days (median 14; range, 6-52 d) and 2.72 ± 0.46 days (median 2.6; range, 2-4 d), respectively. The need for reoperation was seen in 22 patients (13.6%), and 2 patients underwent reoperation twice. Postoperative complications occurred in 30 patients. These included intra-abdominal bleeding in 13 patients, pleural effusion in 10 patients, and bile leakage in 7 patients. The incidence of renal failure was observed in 6 patients (3.7%). There was a significant correlation between LOS and postoperative factors, including ascites, wound infection, bacterial infection, renal failure, pleural effusion, the need for retransplant, and psychiatric problems (P < .05). Linear regression analyses revealed that reoperation, pleural effusion, bacterial infection, and wound infection following LT remained statistically significant factors for LOS after adjusting for other patient factors (Table 4).

Liver transplant is considered as one of the most expensive lifesaving surgical procedures for patients with chronic liver disease. For patients who undergo LT, many factors need to be evaluated to allow better results and to decrease financial expenses at LT centers. The present cross-sectional study was done in a large-volume transplant center that has passed its learning curve.^23,24 In this study, we assessed all variables in all periods (preoperative, intraoperative, and postoperative) of LT procedures that may have impacts on LOS.

Through retrospective analyses of our LT patient registry, 7 variables after LT (BMI, MELD score, length of surgery duration, reoperation, bacterial infection, pleural effusion, and psychiatric problems) were found to be independent predictors of hospital LOS. To date, several studies have been published regarding the determinants of LOS in patients who undergo LT procedures. The impact of donor and recipient variables on LOS varies by centers.^17,18,20 Previous studies from the United States and European countries have often shown inconsistent results regarding survival outcomes after LT in obese patients. This discrepancy in these results may be explained by differences in the definitions of obesity, the pretransplant and posttransplant evaluations, and the sample sizes.^25-28 Our results are consistent with previous reports that indicate that BMI of recipients is significantly associated with prolongation of LOS. Similarly, several large studies have demonstrated that high BMI is independently associated with prolongation of LOS.^27,29-31 In the largest survey done by Hakeem and colleagues27 in the United Kingdom, which included 1325 LT recipients, patients with BMI of 35 kg/m² or greater had a significantly higher duration of both ICU LOS (4.7 vs 3.2 days; P = .03) and hospital LOS (22.4 vs 18.0 days; P = .047) compared with patients with BMI of 18.5 to 24.9 kg/m². Moreover, these findings were in concordance with a recent study done by Singhal and associates,31 which suggested that recipients with a BMI of 40 kg/m² or greater would experience longer duration of ICU and hospital LOS following LT. Although most of these studies did not find any differences in patient and graft survival rates between obese and nonobese recipients, many transplant centers still decline LT candidates with high BMI because of concerns of surgical difficulties and overall outcomes. Therefore, it seems unnecessary to restrict acceptable obese candidates access to transplant surgery.

Our findings confirm that MELD score is independently associated with LOS.³² Similarly, Oberkofler and colleagues³³ reported a significant correlation between MELD score and LOS. Another study reported that increased LOS in the ICU is associated with higher MELD score but failed to find evidence of an effect on mortality.³⁴ Although these studies did not find a clear correlation between MELD score and postoperative mortality, current evidence suggests that high MELD score could influence postoperative morbidity and in turn increase costs. Thus, it appears that patients with high MELD score need to be identified earlier and prioritized for surgery before further clinical deterioration. The recipient factors of BMI and MELD score affect LOS but are less influenced by LT center planning.

Recently, studies have shown that prolonged operative duration is associated with an increased risk of complications and therefore could subsequently result in longer hospital LOS.³⁵The mean operation time in our study was lower compared with the study from Oberkofler and colleagues33 (279.57 ± 52.21 vs 391 ± 90 min). This discrepancy could be explained by the lower mean age of our donors (37.3 vs 48.6 y) and the lower cold/warm ischemia time compared with the previous report. Injury can occur during organ retrieval as a result of relative hypoxic conditions and additional inflammation due to reperfusion.^36,37 Moreover, because of age-related changes, an older donor may be susceptible to injury and have less regenerative capacity.^38,39 However, in this study, we did not find any correlation between cold/warm ischemia time and LOS. According to our study, surgical duration, reoperation, and management of pleural effusion, bacterial infection, and psychiatric problems after LT are factors that affected LOS; these factors should be closely monitored by the LT team.

Among the aforementioned patient-related independent predictors of prolonged hospital LOS among LT recipients, BMI and MELD score are considered as nonmodifiable factors in the setting of transplant centers. On the other hand, we suggest that center-oriented factors, including length of surgery duration and reoperation, can be improved by increasing the experience of the transplant team. In addition, the introduction of comprehensive protocols for better management of other LOS-related risk factors, including bacterial infection, pleural effusion, and psychiatric problems, may hold value for minimizing prolongation of LOS. This pragmatic approach could guide LT centers to conduct more research on the role of these risk factors on LOS trends and may ultimately lead to reducing the financial burden of LT. Based on these findings, we recommend that future studies with larger sample sizes are needed to address these issues.

This study has a number of limitations. First, it is subject to the disadvantages of its retrospective and single-center design. Second, we did not investigate reasons for later readmissions in the first year after LT as a main part of the cost. Third, we did not consider easily measurable but important factors, such as the experience of the transplant team and center, quality, local protocols, and supporting services such as physiotherapists and ICU and ward settings.

Our study showed that factors, including preoperative, intraoperative, and postoperative variables, could have an impact on LOS. Therefore, better methods for being prepared for these factors could reduce adverse outcomes and could also lead to improved patient care and, as a result, resource savings.

Volume: 18 Issue: 3 June 2020

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