Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 6  |  Issue : 1  |  Page : 11-15

Is the bispectral index a sensitive monitor for survival after living donor liver transplantation?


1 Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Mansoura, Egypt; Department of Anesthesiology, King Fahd Hospital of the University of Dammam, Al Khubar, Saudi Arabia
3 Department of Surgery, Gastroenterology Surgical Center, College of Medicine, Mansoura University, Mansoura, Egypt
4 Department of Internal Medicine, College of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission15-Feb-2012
Date of Acceptance01-Apr-2012
Date of Web Publication30-Jun-2014

Correspondence Address:
Mohamed R. El Tahan
MD, Department of Anesthesiology, King Fahd Hospital of the University of Dammam, Al Aqrabiah str., Al Khubar, P.O. Box 40289, 31952 Al Khubar, Saudi Arabia

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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJCA.0000415930.74131.6b

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  Abstract 

Background

Bispectral index (BIS) monitoring has been established as a standard monitoring method for the assessment of the depth of anesthesia during living donor liver transplantation (LDLT). We tested the sensitivity and specificity of BIS readings during LDLT in predicting the postoperative 3-month survival.

Methods

After receiving ethical approval, 42 patients who had undergone LDLT under sevoflurane–fentanyl–rocuronium anesthesia were studied. Correlations between BIS readings and extubation time, postoperative liver function tests, intensive care unit stay, and 3-month mortality were tested. Receiver operating characteristic curves were generated to determine the sensitivity and specificity of the BIS readings during different phases of surgery in predicting the survival outcome.

Results

The extubation time, liver function tests, coagulation factors V and VII, and intensive care unit stay were not statistically correlated with the BIS values. Receiver operating characteristic curve analyses showed reasonable sensitivity and specificity of mean BIS values during hepatic resection and neohepatic periods for predicting the 3-month mortality, with an unweighted accuracy of 76 and 73%, respectively. The nonsurvivors had significantly higher mean BIS values during the neohepatic phase (P<0.05).

Conclusion

The researchers concluded that the BIS monitoring during hepatic resection and neohepatic phases seems to be a suitable noninvasive monitoring tool with reasonable sensitivity and specificity for predicting the 3-month mortality after LDLT under sevoflurane–fentanyl anesthesia.

Keywords: anesthesia, bispectral index, liver transplantation, outcome


How to cite this article:
Yassen AM, El Tahan MR, Salah T, El Shobary M, Sultan A, El Saadany M, Wahab MA. Is the bispectral index a sensitive monitor for survival after living donor liver transplantation?. Egypt J Cardiothorac Anesth 2012;6:11-5

How to cite this URL:
Yassen AM, El Tahan MR, Salah T, El Shobary M, Sultan A, El Saadany M, Wahab MA. Is the bispectral index a sensitive monitor for survival after living donor liver transplantation?. Egypt J Cardiothorac Anesth [serial online] 2012 [cited 2019 Nov 19];6:11-5. Available from: http://www.ejca.eg.net/text.asp?2012/6/1/11/135559


  Introduction Top


The living donor liver transplantation program has been established at the authors’ center since 2004 as a novel therapy for cirrhotic patients with hepatitis, Budd–Chiari syndrome, and hepatocellular carcinoma.

The use of the bispectral index (BIS) has gained widespread popularity among different centers as an optional monitoring tool for the assessment of the depth of anesthesia during liver transplantation 1–5, because it is a noninvasive, simple, and useful tool for the assessment of the peritransplant state of consciousness, especially in the patients with encephalopathy 5. Moreover, BIS readings predict the postoperative graft survival after liver transplantation from the time to emergence from general anesthesia 6.

To the best of the authors’ knowledge, the sensitivity and specificity for BIS monitoring during the three phases of liver transplantation to predict the postoperative survival rate have not yet been identified.

We hypothesized that the BIS readings during the three phases of the living donor liver transplantation would predict the postoperative 3-month mortality rate.

The aim of this study was to examine the relationship between the BIS readings during the hepatic dissection, anhepatic and neohepatic phases and time to extubation, postoperative liver function tests and coagulation factors, and length of intensive care unit (ICU) stay and 3-month mortality after living donor liver transplantation.


  Methods Top


Forty-two American Society of Anesthesiologists physical classes III–IV patients, 20–50 years of age, with severe liver dysfunction (Child–Pugh class C) due to liver cirrhosis, undergoing living donor liver transplantation as a part of the Mansoura University Liver Transplantation Program from 2007 to 2010, were included in this prospective, observational study after obtaining the approval of the local Ethical Committee and a written informed consent from all participants. The study was registered at http://www.ClinicalTrials.gov, with an identification number NCT01494220. The etiology of liver cirrhosis was hepatitis C, Budd–Chiari syndrome, hepatocellular carcinoma, and autoimmune disease.

Patients with pre-existing significant neuropsychiatric, cardiac, pulmonary, renal, neuromuscular, or electrolyte disorders, with BMI greater than 35 kg/m2, who were pregnant, who used antipsychotics or antidepressants, who had alcohol or drug abuse problems, who had had a previous transplantation, and/or who had hepatic encephalopathy, cognitive dysfunction during the past 3 months, fulminant hepatic failure, hepatopulmonary syndrome, or pulmonary hypertension were excluded.

The primary outcome was the influence of intraoperative BIS readings on the postoperative 3-month mortality. The secondary outcome variables included the correlations between BIS readings during the three phases of living donor liver transplantation and time to tracheal extubation, postoperative liver function tests and coagulation factors, and length of ICU stay.

The anesthetic technique was standardized for all patients. All patients preoperatively received 40 mg of pantoprazole intravenously. Patients were monitored by three-lead electrocardiography, pulse oximetry, and noninvasive blood pressure measurement. BIS recording electrodes (Aspect Medical Systems Inc., Norwood, Massachusetts, USA) were placed on the forehead of each patient according to the manufacturer’s recommendations. The BIS monitor was masked with an opaque sheet and BIS data were recorded before induction of general anesthesia and then throughout the procedure. All information obtained from the BIS monitor was downloaded continuously onto a computer for offline analysis. The patients’ management was not guided by the changes in BIS readings. Before induction of anesthesia, all patients were premedicated with 1–2 mg of intravenous midazolam.

Independent anesthetists, who were not involved in the collection and analysis of the patients’ data, were responsible for perioperative anesthetic management. After preoxygenation, anesthesia was induced with 0.75 mg/kg lidocaine, 1.5–2.0 mg/kg propofol, and 2 µg/kg fentanyl. Rocuronium (1–1.2 mg/kg) was administered to suppress the first response on the train-of-four (TOF) stimulations of the ulnar nerve. After tracheal intubation, the lungs were ventilated with an inspired fraction of oxygen (FiO2) of 0.4 to maintain the arterial carbon dioxide tension at 35–45 mm Hg. End-tidal carbon dioxide and sevoflurane concentrations, direct arterial pressure through a radial artery catheter, and tympanic membrane temperature were monitored.

A continuous thermodilution fiberoptic pulmonary artery catheter (CCO/SvO2; Edwards Life Science, Irvine, California, USA) was used to monitor cardiac output.

Anesthesia was maintained with 0.5–1.5 minimum alveolar concentration of sevoflurane and a continuous intravenous infusion of fentanyl (1–3 µg/kg/h) titrated to maintain the mean arterial blood pressure (MAP) and heart rate (HR) within 20% of their baseline values. Rocuronium (0.1–0.3 mg/kg/h) was used to maintain suppression of the second twitch in the TOF.

Normothermia was maintained using intravenous infusions of warm fluid and blood products and a water-filled thermal mattress according to the authors’ protocol. Fluid boluses were administered in 250 ml aliquots of 5% hydroxyethyl starch 130/0.4 (Voluven 6%; Fresenius Kabi, Bad Hombourg, Germany) as needed to maintain the central venous pressure and/or pulmonary artery occlusion pressure between 5 and 7 mm Hg and the stroke volume (SV) within 20% of its baseline value. Albumin (5%) was administered as needed to treat hypoalbuminemia. Salvaged blood from the cell saver and packed red blood cells was transfused as clinically indicated to maintain a hemoglobin level of at least 7 g/dl. Intraoperative changes in electrolyte levels and acid–base balance were monitored regularly and treated as appropriate. Hemodynamic control was standardized according to the protocol in the authors’ center. Hypotension (MAP decrease by <20% from the mean baseline and systemic vascular resistance by <600 dyne/s/cm−5) was treated with boluses of fluids, 5 mg ephedrine, or 5 µg epinephrine, as needed. Norepinephrine infusion was used for persistent hypotension with a low systemic vascular resistance. A dobutamine or epinephrine infusion was administered if the MAP was at least 70 mm Hg, central venous pressure and/or pulmonary artery occlusion pressure was at least 7 mm Hg, and the cardiac output was less than 4.0 l/min. Hypertension (MAP increased by >20% from the mean baseline) was treated with deepening of anesthesia, bolus doses of 0.05 mg nitroglycerin, or 20 mg labetalol. Tachycardia (HR>20% from the baseline values) was treated with boluses of 20 mg esmolol.

All operations were performed by the same surgeons using the piggyback technique. After portal vein clamping, the infusion rates of fentanyl and rocuronium were reduced by ∼50%. Fentanyl and rocuronium infusions were discontinued after peritoneal closure. After the completion of skin closure, sevoflurane was discontinued. The patients were transferred to the ICU immediately after surgery, while intubated, and postoperative analgesia was administered with rescue boluses of 0.5 µg/kg fentanyl when needed. Extubation criteria included cooperativeness, alertness, TOF ratio at least 0.9, spontaneous breathing with tidal volume greater than 5 ml/kg, respiratory rate greater than 10 and lesser than 28 breaths/min, maximum inspiratory pressure up to −20 cm H2O, stable hemodynamics, minimal bleeding, core temperature greater than 35.5°C, urine output greater than 0.5 ml/kg/h, arterial carbon dioxide tension up to 45 mm Hg, arterial oxygen tension greater than 100 mm Hg, and FiO2 less than 50%.

Another investigator, who was not involved in the patients’ management, collected the saved patient data. The preoperative Model for End-Stage Liver Disease (MELD) score, durations of warm ischemia and the anhepatic phase, intraoperative blood loss, and fentanyl consumption were determined. The intraoperative values for BIS, end-tidal concentration of sevoflurane, HR, MAP, cardiac output (CO), and core temperature were recorded preoperatively (baseline), at hepatic dissection, during anhepatic and neohepatic phases, and during surgical closure. Postoperative total bilirubin, albumin level, liver enzymes (aspartate transaminase; alanine transaminase; γ-glutamyl transpeptidase and alkaline phosphatase), prothrombin time, factors V and VII, time to extubation, length of ICU and hospital stays, neurological complications, encephalopathy, and 3-month mortality were recorded.

Data were tested for normality using the Kolmogorov–Smirnov test. Multivariate logistic regression analysis was carried out to identify the correlations between the BIS values and time to tracheal extubation, postoperative liver function and coagulation variables, and length of ICU stay and 3-month mortality.

To evaluate the accuracy of BIS in predicting the survival rate after liver transplantation, receiver operating characteristic (ROC) curves were generated to describe the performance characteristics of the BIS readings during different phases of surgery in predicting the survival outcome. An ROC area of 1.0 is characteristic of an ideal model, whereas an area of 0.5 indicates a model of no diagnostic value. The cutoff values for mortality with the best diagnostic sensitivity and specificity were derived from the ROC curve analyses. Unweighted accuracy [(sensitivity+specificity)/2] was also reported.

The patients studied were further divided according to their outcome variables into survivor (n=32) and nonsurvivor (n=10) subgroups. Independent Student’s t-tests, Mann–Whitney tests, and Fisher exact tests were used as appropriate. Data were expressed as mean (SD), number (%), or median [range]. A value of P less than 0.05 was considered to indicate statistical significance.


  Results Top


All 42 patients with hepatic cirrhosis enrolled completed the study. Patient characteristics including age, sex, weight, height, MELD score, underlying pathology, durations of warm ischemia and anhepatic phase, graft weight/body weight ratio, and durations of surgery and anesthesia are shown in [Table 1]. Intraoperative changes in BIS, end-tidal concentration of sevoflurane, heart rate, MAP, cardiac output, and core temperature are presented in [Table 2]. Outcome data including time to extubation, ICU stay, postoperative liver function tests, activities of factors V and VII, and 3-month mortality are shown in [Table 3].
Table 1: Patients’ characteristics

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Table 2: Intraoperative data

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Table 3: Patients’ outcome

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MELD scores, time to extubation, liver function tests (except for alanine transaminase), activities of factors V and VII, and length of ICU stay were not correlated with the BIS readings during the different phases of liver transplantation [Table 4].
Table 4: Correlations between the bispectral index readings during the different phases of surgery and outcome variables

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The mean BIS values during the hepatic resection and neohepatic phases were significantly correlated to the 3-month mortality (P=0.004 and 0.026, respectively) [Table 4]. Comparative ROC analyses indicated reasonable sensitivity and specificity of the mean BIS values during hepatic resection and neohepatic periods for predicting the 3-month mortality endpoint in the studied patients, with an unweighted accuracy of 76 and 73%, respectively [Figure 1].
Figure 1: Receiver operating curves analyses for BIS during hepatic resection (upper illustration; P=0.008) and neohepatic (lower illustration; P=0.036) phases for 3-month mortality after a living donor liver transplantation. AUC, area under the curve; BIS, bispectral index.

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The characteristics of the survivors and nonsurvivors are presented in [Table 5]. The nonsurvivors had significantly higher mean BIS values and end-tidal concentrations of sevoflurane during the neohepatic phase (P<0.05) [Table 5].
Table 5: Characteristics of the survivors and the nonsurvivors

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We did not encounter any incident of awareness, encephalopathy, or other neurological complications in the studied population.


  Discussion Top


BIS has been used to monitor the depth of anesthesia during liver transplantation to minimize the incidences of intraoperative recall or anesthesia overdepth 1. The validity of BIS in predicting the postoperative survival after living donor liver transplantation has not been studied previously.

The main finding of this study was that the mean BIS values had reasonable sensitivity and specificity for predicting the 3-month mortality during hepatic resection (80 and 72%, respectively) and neohepatic (90 and 57%, respectively) periods. This makes the BIS a simple and noninvasive monitoring tool for the prediction of the short-term outcome after living donor liver transplantation.

The MELD score is used to predict short-term mortality on the waiting list and to allocate liver grafts of patients after liver transplantation 7. Liver transplant patients with high MELD scores require less end-tidal concentrations of inhalational anesthetic during the hepatic resection and the anhepatic periods 2,3. Unfortunately, the nonsurvivors in the present study had significantly higher end-tidal concentrations of sevoflurane during the neohepatic phase.

The present researchers, like others, showed a statistical relation between the postoperative 1-year mortality and the low BIS values in the patients with pre-existing malignant disease 8. There are many independent factors associated with reduced survival after living donor liver transplantation include emergent surgery, Child–Pugh class, United Network for Organ Sharing status 1, and preoperative plasmapheresis 9. In the present study, none of the patients studied underwent an emergent surgery or required preoperative plasmapheresis.

Liver transplantation may result in wide varieties of neurologic abnormalities such as encephalopathy, seizures (myoclonic, focal, or generalized), obtundation, and coma 10. In the current study, the nonsurvivors after living donor liver transplantation had statistically significantly higher mean BIS values than did survivors, although they developed neither postoperative encephalopathy nor other neurological complications. In contrast, other investigators who used target BIS values ranging from 40 to 60 to guide the anesthetic depth in the patients with malignant diseases have confirmed the statistical relationship between low BIS values less than 45 and 1-year mortality 8. This contradictory finding in the present study may be attributed to the occurrence of epileptiform activities after liver transplantation, especially in those with a poor prognosis 11.

The authors of the current study did not encounter any incident of awareness with the nonuse of BIS monitoring for guidance of anesthetic depth.

Further large randomized-controlled studies are required to validate the use of BIS monitoring in predicting short-term and long-term survival after liver transplantation.

The present study has some limitations. First, the authors of the current study did not use the BIS monitor to guide the anesthetic depth during the three phases of liver transplantation to avoid the bias in the accuracy of identification of the predictive effects of the BIS readings on the postoperative outcome. In addition, the authors’ anesthetic management protocol was not associated with any incidence of perioperative awareness or recall. Second, the authors did not include survival data beyond the 3-month period after liver transplantation, because the survival beyond this time is influenced by other factors such as late acute rejection and known late complications of immunosuppressant regimens 12.


  Conclusion Top


BIS monitoring during hepatic resection and neohepatic phases seems to be a suitable noninvasive monitoring tool with reasonable sensitivity and specificity for predicting the 3-month mortality after a living donor liver transplantation under sevoflurane–fentanyl anesthesia.

Acknowledgements

All authors declare that the current research did not receive any financial support from any organization or company.[12]

 
  References Top

1.Wang CH, Chen CL, Cheng KW, Huang CJ, Chen KH, Wang CC, et al. Bispectral index monitoring in healthy, cirrhotic and end-stage liver disease patients undergoing hepatic operation. Transpl Proc. 2008;40:2489–2491  Back to cited text no. 1
    
2.Toprak HI, Sener A, Gedik E, Uçar M, Karahan K, Aydogan MS, et al. Bispectral index monitoring to guide end-tidal isoflurane concentration at three phases of operation in patients with end-stage liver disease undergoing orthotopic liver transplantation. Transpl Proc. 2011;43:892–895  Back to cited text no. 2
    
3.Kang JG, Ko JS, Kim GS, Gwak MS, Kim YR, Lee SK. The relationship between inhalational anesthetic requirements and the severity of liver disease in liver transplant recipients according to three phases of liver transplantation. Transpl Proc. 2010;42:854–857  Back to cited text no. 3
    
4.Schumann R, Hudcova J, Bonney I, Cepeda MS. Availability of anesthetic effect monitoring: Utilization, intraoperative management and time to extubation in liver transplantation. Transpl Proc. 2010;42:4564–4566  Back to cited text no. 4
    
5.Hwang S, Lee SG, Park JI, Song GW, Ryu JH, Jung DH, et al. Continuous peritransplant assessment of consciousness using bispectral index monitoring for patients with fulminant hepatic failure undergoing urgent liver transplantation. Clin Transpl. 2010;24:91–97  Back to cited text no. 5
    
6.Okawa H, Ono T, Hashiba E, Tsubo T, Ishihara H, Hirota K. Use of bispectral index monitoring for a patient with hepatic encephalopathy requiring living donor liver transplantation: a case report. J Anesth. 2011;25:117–119  Back to cited text no. 6
    
7.Rodrigue JR, Nelson DR, Reed AI, Hanto DW, Curry MP. Is model for end-stage liver disease score associated with quality of life after liver transplantation? Prog Transpl. 2011;21:207–214  Back to cited text no. 7
    
8.Lindholm ML, Träff S, Granath F, Greenwald SD, Ekbom A, Lennmarken C, et al. Mortality within 2 years after surgery in relation to low intraoperative bispectral index values and preexisting malignant disease. Anesth Analg. 2009;108:508–512  Back to cited text no. 8
    
9.Tojimbara T, Fuchinoue S, Nakajima I, Kimikawa M, Kitajima K, Ishida H, et al. Factors affecting survival after living-related liver transplantation. Transpl Int. 2000;13(Suppl 1):S136–S139  Back to cited text no. 9
    
10.Ferreiro JA, Robert MA, Townsend J, Vinters HV. Neuropathologic findings after liver transplantation. Acta Neuropathol. 1992;84:1–14  Back to cited text no. 10
    
11.Wszolek ZK, Aksamit AJ, Ellingson RJ, Sharbrough FW, Westmoreland BF, Pfeiffer RF, et al. Epileptiform electroencephalographic abnormalities in liver transplant recipients. Ann Neurol. 1991;30:37–41  Back to cited text no. 11
    
12.Uemura T, Ikegami T, Sanchez EQ, Jennings LW, Narasimhan G, McKenna GJ, et al. Late acute rejection after liver transplantation impacts patient survival. Clin Transpl. 2008;22:316–323  Back to cited text no. 12
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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