Objectives: Postoperative cognitive dysfunction is a serious complication that may be associated with increased mortality. Living-donor liver transplant includes major surgery for the donor. The purpose of this study was to evaluate preoperative and postoperative cognitive function of liver donors in living-donor liver transplant.

Materials and Methods: In 102 patients who had hepatectomy for liver transplant donation, preoperative and postoperative (1 week) neuro-psychologic tests were performed including the Trail Making Test, the Stroop effect, score on the Beck Depression Inventory, and the mini–mental state examination.

Results: Liver transplant donors had significantly lower mean Trail Making A Test duration and greater mean Trail Making B Test error number after than before surgery. The mean Stroop effect reading durations (black and white reading; reading colored words) were significantly greater after than before surgery; the mean time difference between naming the colors of colored words minus reading colored words, and the error number, were smaller after than before surgery. The mean score on the Beck Depression Inventory and mini–mental state examination score were similar before and after surgery.

Conclusions: Mild frontal lobe dysfunction may be present in liver donors at 1 week after surgery, and postoperative attention problems may be experienced by these patients.

Key words : Neuropsychologic testing, Hepatectomy, Mini–mental state examination, Stroop effect, Trail Making Test

Introduction

Postoperative cognitive dysfunction is a short-term decline in cognitive performance after an operation. This problem, which may persist for several weeks to months or may become permanent, is evaluated with neuropsychologic tests.^1,2 Predisposing factors include duration of anesthesia, type of surgery, hypotension, second operation, postoperative infection, respiratory complications, and postoperative pain.³ Preoperative neuropsychologic tests may help diagnose post-operative cognitive dysfunction.² The prevalence of postoperative cognitive dysfunction is 25% to 80% and depends on the definition of postoperative cognitive dysfunction and the time of neuropsychologic testing.⁴ Postoperative cognitive dysfunction is an important complication that may cause social and economic problems for patients and families, and mortality is increased in these patients.⁵ Postoperative cognitive dysfunction may occur after cardiac surgery, but limited information is available about the prevalence of this problem after other types of surgery.⁶

Liver transplant is the only effective treatment for end-stage liver disease.⁷ There are insufficient donor organs available for liver transplant, and living-donor liver transplant is an important option when a deceased-donor organ is not available. It is important to ensure the safety of the donors during organ donation surgery.⁸ Living-donor liver transplant is a long operation that is performed with general anesthesia and may be complicated by microemboli from liver manipulation, ischemic tissue damage, intraoperative hypotension, and postoperative complications.⁹ Postoperative cognitive dysfunction also may occur, but literature search showed no study about postoperative cognitive dysfunction in living donors for liver transplants.

The purpose of the present study was to evaluate preoperative and postoperative cognitive function of liver donors for living-donor liver transplant.

Materials and Methods

Subjects
This study was performed from January 2012 to March 2013 by the Anesthesiology and Reanimation Clinic of the Inonu University Faculty of Medicine. During this period, there were 102 patients (age range, 18 to 65 y; American Society of Anesthesiologists Physical Status, 1 to 2) who had surgery with general anesthesia to donate their liver for living-donor liver transplant. Patients were excluded from the study because of communication problems, illiteracy, insufficient time for tests, use of sedatives, antidepressants or antiepileptic drugs, cerebro-vascular or psychiatric diseases, alcohol or substance abuse, foreign country of origin, or unwillingness to perform postoperative testing. Patients provided informed consent for the study, which was approved by the Malatya Clinical Studies Ethics Committee (permission number 2011/201). All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration.

Testing
The Trail Making Test, the Stroop effect, the score on the Beck Depression Inventory, and the mini–mental state examinations were performed (testing duration, approximately 1 h) with donor patients at 24 hours before surgery by an experienced psychiatrist in an environment with no disruptive stimuli. The demographic data of liver donors were recorded including age, sex, weight, height, education level, relationship to the transplant recipient, socioeconomic status, marital status, number of children, employment status, current diseases, drugs used, information about previous surgery and anesthesia, urgency of surgery, and the presence or absence of an alternative donor. At 1 week after surgery, tests were repeated by the same psychiatrist. The duration of hospitalization duration, postoperative complications, and prognosis were recorded.

Anesthesia
After preoperative hemodynamic values were recorded, anesthesia was induced with lidocaine (2%; 1 mg/kg), fentanyl (1 μg/kg), and thiopental (5 mg/kg), and muscle relaxation was established with vecuronium (0.1 mg/kg). After endotracheal intubation, mechanical ventilation was maintained with oxygen (40%) mixed with air and end-tidal carbon dioxide at 35 to 40 mm Hg. Body temperature was monitored with an esophageal temperature probe. Heating blankets were used to ensure normothermia during surgery. A bispectral index monitor (A-2000 Bispectral Index, Aspect Medical Systems, Norwood, MA, USA) was used to evaluate anesthesia depth. Anesthesia was maintained with isoflurane, remifentanil infusion, and cisatracurium infusion to keep the bispectral index level at 40 to 60. A second peripheral vascular access was maintained with a 16 gauge cannula. Invasive arterial blood pressure was monitored from the left radial artery. When blood loss is more than 20% of total blood volume, a central venous catheter was placed in the internal jugular vein during surgery

Clinical information monitored during surgery included heart rate, mean arterial blood pressure, electrocardiogram, peripheral arterial oxygen saturation, and bispectral index. Information was recorded including surgical method (right or left lobe), duration of Pringle maneuver, amount of hemorrhage and blood replacement, duration of surgery, duration of anesthesia, hypotensive attacks (mean arterial blood pressure < 65 mm Hg), and any complications. Morphine (0.05 mg/kg, intravenous, 30 min before completion of surgery) was injected for postoperative analgesia. Cisatracurium infusion was stopped when the abdominal wall was being closed, and remifentanil infusion was stopped during skin closure. At the end of the operation, muscle relaxation was reversed with neostigmine and atropine as needed. Patients were observed for 30 minutes in the postoperative recovery unit and transferred to the intensive care unit.

Statistical analyses
Data analyses were performed with statistical software (SPSS for Windows, Version 16.0, SPSS Inc., Chicago, IL, USA). Quantitative data were reported as mean ± SD and qualitative data were reported as number (%). Data were tested with Kolmogorov-Smirnov test and comparisons were made with paired t test. Statistical significance was defined by P ≤ .05.

Results

Most liver transplant donors were men who were the parent or sibling of the recipient (Table 1). Most donors had good recipient prognosis and had neither intraoperative hypotension nor intraoperative blood replacement (Table 1). The most frequent complication was infection, and other complications included prolonged hyperbilirubinemia and liver failure, hemorrhage, re-exploration, and pleural effusion (Table 2).

Liver transplant donors had significantly lower mean Trail Making A Test duration and greater mean Trail Making B Test error number after than before surgery (Table 3). The mean Stroop effect reading durations (black and white reading; reading colored words) were significantly greater after than before surgery; the mean time difference between naming the colors of colored words minus reading colored words, and the error number, were smaller after than before surgery (Table 3). The mean score on the Beck Depression Inventory and the mini–mental state examination score were similar before and after surgery (Table 3).

Discussion

The present results showed that liver transplant donors have significant postoperative cognitive dysfunction documented with Trail Making and Stroop effect (Table 3). This is important because previous work showed a relation between postoperative cognitive dysfunction and 1-year mortality.10 Various neuropsychologic tests may quantify postoperative cognitive dysfunction, and the tests used in the present study are valid and reliable for the Turkish population.^11,12

The mini–mental state examination is a short, useful, and commonly used test that enables the evaluation of global cognitive function. This test does not provide an exact diagnosis, but it may measure cognitive deterioration and response to treatment.¹³ In the present study, the mean preoperative and postoperative (1 week) mini–mental state examination values were similar.

Both sections of the Trail Making Test are sensitive to progressive cognitive decline.¹⁴ Trail Making A Test evaluates basic attention, psychomotor speed, and coordination; Trail Making B Test evaluates executive functions. The mean duration of the Trail Making A Test may have decreased after surgery (Table 3) because of learning by repetition of the test. However, the increase in mean error number in the Trail Making B Test after surgery would not have occurred from an effect of learning (Table 3). The subjects may have made more errors after surgery because they may have attempted to complete the test rapidly.¹⁴

The Stroop effect may reflect frontal region activity, and this test measures attention, data processing speed, and the ability to change reaction during interference. The Stroop effect exhibits the ability to change perceptual setup based on varying demands and interference effects, and it evaluates the ability to perform a behavior when suppressing a customary behavior pattern.^15,16 The Stroop effect is sensitive in the early stages of frontal dementia. In the present study, mean times for Stroop 1 (black and white reading) and Stroop 3 effects (reading colored words) were higher, and mean Stroop difference and error number were lower, at 1 week after surgery than before surgery (Table 3). The changes in mean Stroop 1 and 3 effect suggest that the frontal lobe might have been affected mildly and that attention problems occurred after surgery. The decrease in mean Stroop effect time difference and error number may have occurred because of an effect of learning and the short time (1 week) between test repetition.

Increased age is a risk factor for prolonged irreversible postoperative cognitive dysfunction. Aging is associated with decreased cognitive reserves and decreased ability to tolerate or recover from trauma. In surgery other than major heart surgery, the frequency of postoperative cognitive dysfunction for patients aged 60 to 69 years is 23% and for patients aged > 70 years is 29% (frequency for healthy control patients, 3.4%).²

Intraoperative monitoring the depth of anesthesia is beneficial for decreasing the incidence of postoperative cognitive dysfunction.¹⁷ Monitoring bispectral index during anesthesia may decrease postoperative cognitive dysfunction by decreasing exposure to anesthetic agents.¹⁸ In the present study, the patients were monitored for bispectral index and anesthetic agents were titrated to maintain bispectral index from 40 to 60. With short-acting agents such as propofol and desflurane, cognitive function evaluated with the mini–mental state examination may improve to preoperative levels within 1 day after surgery.¹⁹ In the present study, there was no difference between mean preoperative and postoperative (1 week) mini–mental state examination score (Table 3), possibly because short-acting agents (isoflurane and remifentanil) were used.

Limitations of the present study include the short-term evaluation and lack of a control group. The present subjects were retested 1 week after surgery. The timing of testing for postoperative cognitive dysfunction may vary between different studies. Early cognitive decline of 30% to 50% during the first postoperative week may decrease to 10% within 3 months after surgery.²⁰

In summary, living-donor liver transplant may have postoperative complications that may cause donor morbidity and mortality. The Trail Making and the Stroop effect showed that mild frontal lobe dysfunction was present in liver donors at 1 week after surgery, and postoperative attention problems may be experienced by these patients. Further studies are justified to evaluate long-term postoperative cognitive function and clinical relevance of the abnormal neuropsychologic findings in these patients.

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