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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 2  |  Page : 136-140

The relationship between postoperative outcomes and delirium after liver transplantation in intensive care unit: A single-center experience


1 Department of Intensive Care Unit, Ankara Sehir Hastanesi, Ankara, Turkey
2 Department of Gastrointestinal Surgery, Ankara Sehir Hastanesi, Ankara, Turkey

Date of Submission08-Aug-2019
Date of Acceptance15-Mar-2020
Date of Web Publication06-Jul-2020

Correspondence Address:
Dr. Ibrahim Mungan
Department of Intensive Care Unit, Ankara Sehir Hastanesi, Bilkent, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_31_19

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  Abstract 


Context: The incidence of delirium has been reported to be as high as 47% after liver transplantation (LT) and hepatic encephalopathy, acute kidney injury, the usage of calcineurin inhibitors, or high-dose steroids are accused as the reason for delirium. Aims: We aimed to evaluate the incidence of delirium and the relations with preoperative variables and postoperative outcomes after LT. Settings: In this single-center, retrospective, observational study, all patients who received an LT from 2015 to 2018 were enlisted. Subjects and Methods: The data were assessed by the Confusion Assessment Method for the Intensive Care Unit and Delirium Rating Scale-revised version to find the presence and the severity of delirium. Statistical Analysis Used: Spearman's rho test and Mann–Whitney U-test of contingency were used in this study. Results: During the study, 43 consecutive patients underwent LT and 10 patients (23.3%) developed delirium postoperatively. Intraoperative and postoperative features were not significantly different between the two groups, and the delirium onset day was found to be 5 ± 4.8 and the duration of delirium was 3.1 ± 2.23 days. There was no statistically significant relationship between delirium and postoperative outcomes. Conclusions: Delirium could be considered a cause or a consequence of critical illness and psychiatric disorder. Although in the present study, a statistically significant difference was not detected between delirium and outcomes after surgery, it was shown that the morbidity rate increases with delirium.

Keywords: Delirium, intensive care unit, morbidity, outcomes


How to cite this article:
Mungan I, Türksal E, Sari S, Bostanci EB, Turan S. The relationship between postoperative outcomes and delirium after liver transplantation in intensive care unit: A single-center experience. Indian J Transplant 2020;14:136-40

How to cite this URL:
Mungan I, Türksal E, Sari S, Bostanci EB, Turan S. The relationship between postoperative outcomes and delirium after liver transplantation in intensive care unit: A single-center experience. Indian J Transplant [serial online] 2020 [cited 2020 Aug 5];14:136-40. Available from: http://www.ijtonline.in/text.asp?2020/14/2/136/289038




  Introduction Top


Delirium is a distortion and fluctuation in cognitive functions such as memory, orientation, and the perception that evolves within days or weeks after provoking factors such as surgery. The incidence of delirium has been reported to be as high as 87% in patients admitted to the intensive care unit (ICU) after surgery and 47% after liver transplantation (LT) in living donor organ recipients.[1] This common neuropsychiatric disorder has been associated with worse outcomes after LT, as in other critically ill populations.[2]

The actual data on delirium after LT are scarce. Previous studies on this topic in the literature mainly focused on the risk factors and outcomes such as the length of stay (LOS) in hospital and in ICU and mortality.[1],[3] Nevertheless, this deteriorating clinical finding is frequently unnoticed or misdiagnosed in LT patients, and this leads to inappropriate or late treatment. It has been shown that awareness about delirium and quick response with appropriate treatment decreases morbidity.[4],[5] Especially, intensivists should be able to identify and manage delirium as soon as possible while the atypical and confusing presentation of delirium multifactorial nature causes complexity and difficulty.

Different researchers find delirium incidence with varying rates, and the provoking reasons for delirium are mainly metabolic, infections, and drug related.[5] Particularly in LT patients, hepatic encephalopathy, acute kidney injury (AKI), the usage of calcineurin inhibitors, or high-dose steroids are also implicated in delirium.[2]

Besides that, the disease severity scores on admission to ICU such as Model for End-Stage Liver Disease (MELD) score, Child–Pugh score, as well as the mortality predictor scores such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score were claimed to be related to delirium. Identifying these relations and predictors helps early diagnosis and prevention of delirium, especially in high-risk patients.[6],[7] We aimed to evaluate the incidence of delirium and the relations with preoperative variables and postoperative outcomes after LT in our ICU.


  Subjects and Methods Top


In this single-center, retrospective, observational study, all patients who received an LT from January 1, 2015, to July 31, 2018, at a tertiary state hospital in Ankara were enlisted. Patients older than 18 years old, and ICU stay > 24 h were included. Only living donor LT recipients were included in this study to decrease the effect of variability. Exclusion criteria were incomplete laboratory datasets, intracranial hemorrhage, primary graft dysfunction of the liver, and the requirement for reoperation after LT (n = 62).

[Figure 1] describes the study population and the characteristics of the excluded patients. As a routine procedure, all patients were started on tacrolimus-based immunosuppression after LT.
Figure 1: Flowchart of the study population

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The present study was in the category of noninterventional clinical research, and no ethics committee approval was applied and extra formal consent other than the patients or relatives had given before hospitalization was not required. It was a case–control medical record (MR) review. This situation is in line with the National Code of Clinical Research which was published on April 13, 2013.[8] This study adhered to the principles in accordance with the Helsinki Declaration of 1975, as revised in 2008.

To define the patients with delirium, the MRs including notes from intensivists, primary physicians, and occupational therapists as well as nurse report sheets and the neurologic and/or psychiatric consult service requests of LT recipients were reviewed for a diagnosis of delirium.

At first, all patients were evaluated by the Richmond Agitation and Sedation Scale (RASS), and if the score was >+3 or <−3, the data were not evaluated further. After this initial evaluation, the data were assessed by two major neuropsychological screening (valuation) tools to find the presence and severity of delirium, Confusion Assessment Method for the ICU (CAM-ICU), and Delirium Rating Scale-revised version (DRS-R-98).[9],[10] The DRS-R-98 has 2 parts, 13 severity components and 3 diagnostic components, while CAM-ICU consists of 9 criteria derived from the DSM III-R.

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. The present study was in the category of noninterventional clinical research, and no ethics committee approval was applied and this situation is in line with the National Code of Clinical Research which was published on April 13, 2013.

Data collection

Patients' demographic and characteristic data, details of transplant surgery, and postoperative hospital continuum were collected from the MR as well. The data on the admission of ICU were also used to calculate the Charlson Comorbidity Index, MELD score, Child–Pugh score, APACHE II score, Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) score. These scores were utilized to find any relation with the delirium variable. The study population was divided into two groups based on the presence or absence of delirium, and delirium-positive patients were further evaluated for the onset and duration of delirium period.

The duration of surgery, donor type, and the laboratory findings 7 days after LT were compared regarding delirium variable. We considered the postoperative 7th day as the appropriate time for laboratory results to compare regarding delirium because, in most studies, delirium onset was in the first or second week postoperatively. Moreover, even 88% delirium happened on the 1st postoperative day in a recent study.[3],[6]

The duration of mechanical ventilator support, information about postoperative outcomes, and complications (renal, neurologic, and infectious) were collected. Renal failure was defined as the presence of oliguria (<0.5 ml/kg/h), the optimization of fluid loading, and a doubling of post-LT creatinine values with the need for renal replacement therapy (hemodialysis or filtration). This definition was corresponding to Stages 2 and 3 according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI.[11] The neurological complication was defined as the presence of clinical or radiological evidence for a neurological deficit or defect, for example, stroke, severe cerebral bleeding, or severe cerebral edema. Mortality as a variable in this study was described as death from any cause occurring in the hospital after LT.

Laboratory values mainly for blood urea nitrogen (BUN), creatinine, alkaline phosphatase, total bilirubin, sodium, international normalized ratio, and tacrolimus concentration were collected as variables.

Statistical analysis

Statistical analysis was performed using SPSS version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Data were analyzed, and continuous variables were reported as mean ± standard deviation and nominal variables were reported as total number and percentages.

The statistical tests – either parametric or nonparametric tests – were selected based on an assessment of normality through the one-sample Kolmogorov–Smirnov test. The results showed that nonparametric test utilization would be appropriate. The correlations between continuous variables were assessed using the Spearman's rho test, and categorical variables were assessed by the Mann–Whitney U-test of contingency. In all analyses, P < 0.05 was considered statistically significant.


  Results Top


During the study, 43 consecutive patients underwent LT and 10 patients (23.3%) developed delirium postoperatively. The mean age was 49.4 ± 10.4 years ranging between 22 and 64. Statistically, no significant difference was observed between the patients with and without delirium considering age, gender, past medical history, disease severity scores such as Child–Pugh score, or indication of transplantation [Table 1].
Table 1: Demographic and clinical characteristics of the patients (n=43)*

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Intraoperative and postoperative features were not significantly different between the two groups [Table 2]. [Table 3] lists the clinical features of patients who developed delirium. The delirium onset day was found to be 5 ± 4.8, and the duration of delirium was 3.1 ± 2.23 days.
Table 2: Intraoperative and postoperative clinical parameters*

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Table 3: Delirium outcomes in the study sample

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Postoperative variables and outcomes are summarized in [Table 4], and there was no statistically significant relationship with delirium factor.
Table 4: Postoperative outcomes and relation with delirium factor*

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The mean tacrolimus level was 8.8 ± 3.8 and it was similar in both the groups, and only in seven patients, a supratherapeutic level > 12 ng/ml was detected. This variable was irrelevant to the delirium factor.

The inhospital mortality rate in delirium patients was 10% (vs. 0% in the nondelirium group), but this was not statistically significant (P = 0.07). The duration of mechanical ventilation requirement in patients with delirium (2.6 vs. 0.8 days, P = 0.19), duration of ICU stay (15.8 vs. 12.6 days, P = 0.43), and duration of hospitalization (51.8 vs. 44.2 days, P = 0.72) were longer than the nondelirium group, but these differences were not statistically significant.

The complication rate for neurologic, infectious, and renal differed between the groups was greater in the delirium group, while the differences were not significant statistically. However, if the KDIGO stage was considered as a variable, not an acute renal failure, significance was observed (P = 0.04).


  Discussion Top


Multiple determinants are playing a role in the onset of delirium, whereas the patient's prehospital status and severity of disease which necessitate ICU admission are the major implicated factors.[12] In our study, the delirium (+) group represented 23.3% of LT recipients, and this rate complies with the literature in which the reported incidence of delirium in LT recipients is about 9. 8%–47.4%.[7],[13]

In our study, no significant difference was detected between the groups regarding liver disease severity scores – MELD score, Child–Pugh score – or critical care assessment scores – APACHE II, SOFA score, and SAPS score – unlike Wang et al.'s [7] study which correlated delirium with a higher APACHE II score. In this context, our findings were similar to Lescot et al.'s study.[12]

The prehospital psychiatric disorder was present in three patients in the nondelirium group, unexpectedly none in the delirium group, and this finding was in contradiction to Oliver et al.'s [1] study which claimed prehospital depression as an independent risk factor for delirium. Infectious complications were also shown to be related to mental alterations; however, no significant difference was detected between the groups in our study.[2],[14]

Fann [15] study claimed that pretransplant elevated BUN level correlated with delirium, whereas in our study, no significant difference was detected with pretransplant laboratory values. Even though in our retrospective analysis, no neurotoxic adverse effect of tacrolimus was detected in the MR of the patients, calcineurin inhibitors are declared to be related to delirium, especially in supratherapeutic levels.[1]

Prior studies have displayed that delirium is related to increased morbidity and mortality rates and prolonged LOS in ICU. In a recent prospective cohort study, the incidence of delirium after LT was found 45.2% and associated with longer LOS in ICU and inhospital, whereas in our study, the difference was not significant statistically regarding these variables.[16] We found a smaller incidence rate of delirium which may be due to the shorter duration of follow-up time – only, the ICU period was assessed. The delirium onset time was 5 ± 4.8 days postoperatively, and this was in concurrence with the previous studies, whereas the duration of delirium was shorter (3.1 ± 2.23). Delirium management was not discussed in the present study because multiple factors besides antipsychotic therapy affect delirium progress or treatment.[17]


  Conclusions Top


Delirium could be considered either a reason or a result of critical illness and psychiatric disorder. Although in the present study, a statistically significant difference was not detected between delirium and outcomes after surgery, it was shown that the duration of mechanical ventilation requirement, duration of ICU stay, and duration of hospitalization were longer. In this context, prompt prevention and awareness about delirium become substantial, especially in high-risk patient populations such as LT recipients.

Limitations

Even though the retrospective nature of the present study may be censurable as a cause of the low rate of delirium incidence, as it is mentioned in the material method section, a thorough investigation for delirium was done through MR, and this accused data bias should have little effect. Not only CAM-ICU but also DRS-98 was utilized to diagnose delirium to eliminate bias about diagnosis accuracy. The small sample size is the second limitation that may obscure possible correlations of delirium with pretransplant and postoperative variables.

Acknowledgment

The authors of this original article certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Oliver N, Bohorquez H, Anders S, Freeman A, Fine K, Ahmed E, et al. Post-liver transplant delirium increases mortality and length of stay. Ochsner J 2017;17:25-30.  Back to cited text no. 1
    
2.
Bhattacharya B, Maung A, Barre K, Maerz L, Rodriguez-Davalos MI, Schilsky M, et al. Postoperative delirium is associated with increased intensive care unit and hospital length of stays after liver transplantation. J Surg Res 2017;207:223-8.  Back to cited text no. 2
    
3.
Piñero F, Cheang Y, Mendizabal M, Cagliani J, Gonzalez Campaña A, Pages J, et al. Incidence, risk factors, and outcomes related with neurological events after liver transplantation in adult and pediatric recipients. Pediatr Transplant 2018;22:e13159.  Back to cited text no. 3
    
4.
Weckmann MT, Gingrich R, Mills JA, Hook L, Beglinger LJ. Risk factors for delirium in patients undergoing hematopoietic stem cell transplantation. Ann Clin Psychiatry 2012;24:204-14.  Back to cited text no. 4
    
5.
Te HS. Altered mental status after liver transplant. Clin Liver Dis (Hoboken) 2017;10:36-41.  Back to cited text no. 5
    
6.
Lee H, Oh SY, Yu JH, Kim J, Yoon S, Ryu HG. Risk factors of postoperative delirium in the intensive care unit after liver transplantation. World J Surg 2018;42:2992-9.  Back to cited text no. 6
    
7.
Wang SH, Wang JY, Lin PY, Lin KH, Ko CJ, Hsieh CE, et al. Predisposing risk factors for delirium in living donor liver transplantation patients in intensive care units. PLoS One 2014;9:e96676.  Back to cited text no. 7
    
8.
National Code on Clinical Researches Published in Official Gazette Numbered with 28030 At April 13, 2013.  Back to cited text no. 8
    
9.
Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the delirium rating scale-revised-98: Comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci 2001;13:229-42.  Back to cited text no. 9
    
10.
Wu SY, Chen TW, Feng AC, Fan HL, Hsieh CB, Chung KP. Comprehensive risk assessment for early neurologic complications after liver transplantation. World J Gastroenterol 2016;22:5548-57.  Back to cited text no. 10
    
11.
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1-138.  Back to cited text no. 11
    
12.
Lescot T, Karvellas CJ, Chaudhury P, Tchervenkov J, Paraskevas S, Barkun J, et al. Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients. Can J Gastroenterol 2013;27:207-12.  Back to cited text no. 12
    
13.
Piñero F, Mendizabal M, Quiros R, Fauda M, Arufe D, Gonzalez Campaña A, et al. Neurological events after liver transplantation: A single-center experience. Transpl Int 2014;27:1244-52.  Back to cited text no. 13
    
14.
Ritter C, Tomasi CD, Dal-Pizzol F, Pinto BB, Dyson A, de Miranda AS, et al. Inflammation biomarkers and delirium in critically ill patients. Crit Care 2014;18:R106.  Back to cited text no. 14
    
15.
Fann JR. The epidemiology of delirium: A review of studies and methodological issues. Semin Clin Neuropsychiatry 2000;5:64-74.  Back to cited text no. 15
    
16.
Beckmann S, Schubert M, Burkhalter H, Dutkowski P, De Geest S. Postoperative delirium after liver transplantation is associated with increased length of stay and lower survival in a prospective cohort. Prog Transplant 2017;27:23-30.  Back to cited text no. 16
    
17.
Ya-Lie K. To explore delirium in liver transplant ICU patients and its management. J Intensive Crit Care Nurs 2018;1:4-8.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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