G Model YDLD-2881; No. of Pages 6
ARTICLE IN PRESS Digestive and Liver Disease xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Liver, Pancreas and Biliary Tract
Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients夽 Amit Jindal, Barjesh Chander Sharma ∗ , Sanjeev Sachdeva, Rajiv Chawla, Siddharth Srivastava, Sudhir Maharshi Department of Gastroenterology and Anaesthesiology, G.B. Pant Hospital, New Delhi, India
a r t i c l e
i n f o
Article history: Received 10 October 2014 Accepted 28 April 2015 Available online xxx Keywords: Ammonia Chronic liver disease Minimal hepatic encephalopathy Overt hepatic encephalopathy Psychometric hepatic encephalopathy score Psychometric tests
a b s t r a c t Background: Recent evidence suggests that bispectral index may aid in the diagnosis of hepatic encephalopathy. We evaluated its utility to diagnose, grade and monitor clinical course of hepatic encephalopathy in patients with cirrhosis. Methods: 200 patients (70.5% males, mean age 39.5 ± 9.1 years) with cirrhosis and 20 healthy controls were enrolled prospectively. Cirrhotic patients were divided into groups based on encephalopathy grades I–IV assessed by West Haven criteria; minimal encephalopathy was assessed by psychometric tests. Bispectral index was measured at baseline and after one week of lactulose therapy in patients with overt encephalopathy, and after 3 months in patients with minimal encephalopathy. Results: Bispectral index scores were significantly different in patients with different grades of encephalopathy; 79.5 ± 4.2, 67.5 ± 4.3, 56.4 ± 3.5, 44.8 ± 3.9 and 85.0 ± 4.3 respectively for grade I, II, III, IV overt and minimal hepatic encephalopathy, but similar (92.6 ± 3.7 vs 93.75 ± 2.8) in cirrhotics without encephalopathy and healthy controls. Bispectral scores’ cut off values for minimal and overt encephalopathy grade I, II, III, IV were 90.5 and 77.5, 70.5, 60.5, 50.5, respectively. Changes in bispectral index after treatment corresponded to cut-off scores for grades of overt and minimal hepatic encephalopathy. Conclusions: Bispectral index was found to be useful in diagnosis, grading and monitoring of treatment response in cirrhotic patients with hepatic encephalopathy. © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction diagnosed after exclusion of other known causes [1]. HE is a challenging complication of advanced liver disease, occurring in approximately 30–45% of patients with cirrhosis [2,3] and 10–50% of patients with transjugular intrahepatic portosystemic shunt [4,5]. HE is broadly divided into overt and minimal HE (MHE). MHE represents the mildest form of HE in which there are no clinically overt symptoms, but patients have abnormal neuropsychologic and/or neurophysiologic findings indicative of
夽 Clinical Trial Registry-India (CTRI) Registration No.: CTRI/2014/03/004493. ∗ Corresponding author at: Department of Gastroenterology, Room No. 203, Academic Block, G.B. Pant Hospital, New Delhi 110002, India. Tel.: +91 1123234242x5203; fax: +91 1123219222. E-mail address: [email protected] (B.C. Sharma).
cerebral dysfunction [6]. The prevalence of MHE in cirrhosis varies from 30 to 80% in various studies [7,8]. The International Working Party acknowledged the difficulties associated with the diagnosis of HE [1]. It was suggested that this condition is best diagnosed by combining clinical grading of the mental state using West Haven criteria [9], psychometric tests [10], and where possible a quantitative neurophysiological measure such as electroencephalography (EEG). However, psychometric tests are only suitable above a certain age and educational background [10], while EEG is time consuming and not always readily available. Also, most clinical systems are mired in subjectivity until the end stage of coma is reached and are not reproducible among examiners [11], with a lack of objectivity in clinical diagnosis of HE. West Haven criteria are used for staging overt HE while neuropsychiatric and neurophysiological tests (psychometric hepatic encephalopathy score) are used for diagnosis of MHE. However objective methods for evaluation of the entire spectrum of no, minimal and overt HE are lacking [12]. Also, as yet there is no gold standard for grading or monitoring the progression of HE.
http://dx.doi.org/10.1016/j.dld.2015.04.014 1590-8658/© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jindal A, et al. Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.04.014
G Model YDLD-2881; No. of Pages 6
ARTICLE IN PRESS A. Jindal et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
2
The Bispectral index (BIS) is a recent technology used to measure the effects of anaesthetics and sedatives on the brain and consciousness. It uses a complex mathematical algorithm based upon descriptive EEG parameters from the frontal cortex to suggest various levels of sedation. BIS is the weighted sum of three sub parameters: “Beta Ratio”, a frequency domain feature; relative synchrony of fast and slow wave, “SynchFastSlow”, a bispectral domain feature; and “Burst suppression ratio”, a time domain feature. The BIS analysis uses a proprietary algorithm that allows different descriptors to dominate sequentially as the EEG changes its character [13]. A sensor placed on the patient’s forehead sends raw EEG waveforms to the monitor, where they are analyzed and the BIS index is calculated which ranges from 0 (isoelectric EEG) to 100 (completely awake) [13,14]. A recent study by Dahaba et al. [15] has shown the utility of BIS in overt HE and concluded that it is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease. We aimed to evaluate the role of BIS to diagnose minimal and overt HE, to grade HE levels, and monitor the response of overt HE and minimal HE to treatment.
2. Patients and methods The study was conducted in the Department of Gastroenterology at G. B. Pant Hospital, New Delhi, India from February 2014 to September 2014. It was a prospective case control, observer blinded study evaluating the role of BIS in patients with overt and minimal HE (Clinical Trial Registration number, CTRI/2014/03/004493). Consecutive cirrhotic patients attending the outpatient department or admitted to the Gastroenterology ward of GB Pant Hospital were eligible for the study. Written informed consent was obtained from each patient (and/or guardian); the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki was approved by the institutional review committee. Patients with liver cirrhosis (aged 18–70 years) were prospectively enrolled. Exclusion criteria were: use of sedatives, hypnotics or psychotropic drugs; concomitant neurological disorders affecting the mental state such as stroke, stupor, or dementia; lactulose therapy during the previous 6 weeks and history of recent alcohol intake (in the past 6 months). Diagnosis of cirrhosis was based on clinical, biochemical, ultrasonographic and liver histological findings if available. All cirrhotic patients without overt HE were screened for MHE. Diagnosis and grading of overt HE was done according to West Haven criteria. MHE was diagnosed according to Psychometric hepatic encephalopathy score (PHES score). PHES evaluation included digit symbol test (DST), number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT) and line-tracing test (LTT). A test was considered abnormal when the score was beyond ±2 SD from the score in the age and education-matched control group. MHE was diagnosed when the sum of all scores ≤−5 points [16]. Patients were evaluated for the aetiology and severity of liver disease (Child Turcotte Pugh [CTP] and Model for End-stage Liver Disease [MELD] score). The level of consciousness was assessed in patients with overt HE using Glasgow coma scale (GCS). Patients in the overt HE group (n = 120) received lactulose (30 ml two to three times daily orally or via nasogastric tube in cases of unconscious patients, to obtain 2–3 soft stools/day) for 7 days and their grades of HE were reassessed and recorded after 7 days. Patients in the MHE group (n = 60) received lactulose (30 ml two to three times daily orally to obtain 2–3 soft stools/day) for three months. All investigations and PHES scoring were repeated after
3 months of therapy. We also enrolled 20 patients with cirrhosis without HE, and 20 age and gender-matched healthy controls. All patients underwent complete blood count, liver function tests, serum electrolytes, serum creatinine, work up for aetiology of liver disease (including viral markers, history of alcohol intake, autoimmune liver disease, Wilson’s disease, lipid profile, blood sugar, body mass index, anti mitochondrial antibody, perinuclear anti-neutrophil cytoplasmic antibody) and arterial ammonia. 2.1. Bispectral index (BIS) recording We recorded BIS for all cirrhotic patients with overt HE/MHE along with cirrhotics without HE/MHE. Immediately before the BIS recording, the grade of overt HE was assessed clinically according to West Haven criteria and MHE by PHES score. Thereafter, a blinded anaesthesiologist recorded the BIS data in a quiet environment over an artefact-free period of 10 min, which took up to 15 min of total recording time. All noise, as well as verbal or tactile stimulation was avoided, thus preventing external stimuli from provoking a transient BIS response [17]. A BIS “Quatro” sensor strip was placed on the patient’s forehead according to the manufacturer’s instructions and connected to a BIS-XP monitor (version 3.4, Aspect Medical Systems, Newton, Massachusetts, USA). The BIS monitor was either connected to a laptop computer or to a printer for recording of BIS value. Conscious patients were instructed to remain calm with their eyes closed but not to fall asleep [18], and to try to keep their facial muscles completely relaxed [19]. Recordings were started after verifying a sustained low electromyography (EMG) activity and a signal quality index above 95%. Data from BIS index and EMG power, displayed in decibel (dB) units, were continuously collected and stored once every five seconds and at end of 10 min, mean BIS score was recorded. As BIS increases spuriously with high EMG activity [19], agitated patients with high EMG activity were excluded from the study and only recordings with low EMG activity and without technical artefacts (such as unexpected noise or unavoidable external stimulation) were accepted for analysis. Because BIS decreases with sleep [18], all conscious patients were interviewed at the end of the recordings, and patients who fell asleep during recording of BIS value were excluded from the study. We also recorded BIS score in 20 patients of liver cirrhosis without overt HE and MHE based on West Haven criteria and PHES respectively, and in 20 healthy controls at baseline. 2.2. Study follow up Patients with overt HE group were reassessed clinically after 7 days for the grade of HE, and at this time, the observer (anaesthesiologist) blinded to HE grade recorded the second BIS score. Patients with MHE were reassessed for the PHES score after 3 months. 2.3. Statistical analysis To date there is no data on BIS monitoring before and after lactulose therapy in patients of overt HE/MHE to allow prior sample size calculation. We enrolled 200 cirrhotic patients (30 each of overt HE grade I, II, III and IV, 60 of MHE and 20 without HE). Data were expressed as mean ± SD or median (range). The BIS cut off values for HE grade I was calculated as the mean of the lowest BIS value in HE grade I patients and the highest value in HE grade II patients, and in the same way was calculated for the other grades and patients of MHE and without encephalopathy. Comparison of BIS values in different grades of overt HE/MHE at baseline was done using two way analysis of variance (ANOVA) test followed by post hoc analysis (by Bonferroni method).
Please cite this article in press as: Jindal A, et al. Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.04.014
G Model
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A. Jindal et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
3
Table 1 Baseline demographic parameters, laboratory parameters and aetiology in the study groups. Parameter
Cirrhotics without HE (n = 20)
Cirrhotics with MHE (n = 60)
Cirrhotics with overt HE (n = 120)
p-Value
Mean age (years) Male gender (%) Mean CTP score Mean GCS Mean MELD score Mean arterial ammonia (mol/l) Aetiology Alcohol HBV HCV Cryptogenic Other
40.3 ± 12.1 12 (60%) 8.9 ± 1.8 15 13 ± 4 67.3 ± 24.9
42.6 ± 11.2 39 (65%) 9.2 ± 2.5 15 19 ± 5.4 70.3 ± 23.7
38.3 ± 10.3 90 (75%) 10.5 ± 1.87 11.5 ± 0.9 22.9 ± 4.6 90.5 ± 19.6
0.73 0.12 0.02 – 0.04 0.03
31 (52%) 11 (19%) 7 (11%) 9 (15%) 2 (4%)
60 (50%) 21 (17%) 13 (11%) 17 (14%) 9 (8%)
0.45
9 (45%) 4 (20%) 3 (15%) 3 (15%) 1 (5%)
HE: hepatic encephalopathy, MHE: minimal hepatic encephalopathy, CTP: Child Turcotte Pugh, GCS: Glasgow coma scale, MELD: model for end stage liver disease, HBV: hepatitis B virus, HCV: hepatitis C virus.
Receiver-operating characteristic (ROC) curves for BIS predictive value of West Haven grades were constructed, and the areas under the curves (AUC) were calculated and again BIS cut off was calculated. Correlation of mean BIS value/HE grades with arterial ammonia levels, CTP score and MELD score was assessed by using Spearman’s rank correlation analysis. Comparison of BIS values before & after treatment was performed using Student’s paired t test. ‘p’ value of
ARTICLE IN PRESS Digestive and Liver Disease xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Liver, Pancreas and Biliary Tract
Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients夽 Amit Jindal, Barjesh Chander Sharma ∗ , Sanjeev Sachdeva, Rajiv Chawla, Siddharth Srivastava, Sudhir Maharshi Department of Gastroenterology and Anaesthesiology, G.B. Pant Hospital, New Delhi, India
a r t i c l e
i n f o
Article history: Received 10 October 2014 Accepted 28 April 2015 Available online xxx Keywords: Ammonia Chronic liver disease Minimal hepatic encephalopathy Overt hepatic encephalopathy Psychometric hepatic encephalopathy score Psychometric tests
a b s t r a c t Background: Recent evidence suggests that bispectral index may aid in the diagnosis of hepatic encephalopathy. We evaluated its utility to diagnose, grade and monitor clinical course of hepatic encephalopathy in patients with cirrhosis. Methods: 200 patients (70.5% males, mean age 39.5 ± 9.1 years) with cirrhosis and 20 healthy controls were enrolled prospectively. Cirrhotic patients were divided into groups based on encephalopathy grades I–IV assessed by West Haven criteria; minimal encephalopathy was assessed by psychometric tests. Bispectral index was measured at baseline and after one week of lactulose therapy in patients with overt encephalopathy, and after 3 months in patients with minimal encephalopathy. Results: Bispectral index scores were significantly different in patients with different grades of encephalopathy; 79.5 ± 4.2, 67.5 ± 4.3, 56.4 ± 3.5, 44.8 ± 3.9 and 85.0 ± 4.3 respectively for grade I, II, III, IV overt and minimal hepatic encephalopathy, but similar (92.6 ± 3.7 vs 93.75 ± 2.8) in cirrhotics without encephalopathy and healthy controls. Bispectral scores’ cut off values for minimal and overt encephalopathy grade I, II, III, IV were 90.5 and 77.5, 70.5, 60.5, 50.5, respectively. Changes in bispectral index after treatment corresponded to cut-off scores for grades of overt and minimal hepatic encephalopathy. Conclusions: Bispectral index was found to be useful in diagnosis, grading and monitoring of treatment response in cirrhotic patients with hepatic encephalopathy. © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction diagnosed after exclusion of other known causes [1]. HE is a challenging complication of advanced liver disease, occurring in approximately 30–45% of patients with cirrhosis [2,3] and 10–50% of patients with transjugular intrahepatic portosystemic shunt [4,5]. HE is broadly divided into overt and minimal HE (MHE). MHE represents the mildest form of HE in which there are no clinically overt symptoms, but patients have abnormal neuropsychologic and/or neurophysiologic findings indicative of
夽 Clinical Trial Registry-India (CTRI) Registration No.: CTRI/2014/03/004493. ∗ Corresponding author at: Department of Gastroenterology, Room No. 203, Academic Block, G.B. Pant Hospital, New Delhi 110002, India. Tel.: +91 1123234242x5203; fax: +91 1123219222. E-mail address: [email protected] (B.C. Sharma).
cerebral dysfunction [6]. The prevalence of MHE in cirrhosis varies from 30 to 80% in various studies [7,8]. The International Working Party acknowledged the difficulties associated with the diagnosis of HE [1]. It was suggested that this condition is best diagnosed by combining clinical grading of the mental state using West Haven criteria [9], psychometric tests [10], and where possible a quantitative neurophysiological measure such as electroencephalography (EEG). However, psychometric tests are only suitable above a certain age and educational background [10], while EEG is time consuming and not always readily available. Also, most clinical systems are mired in subjectivity until the end stage of coma is reached and are not reproducible among examiners [11], with a lack of objectivity in clinical diagnosis of HE. West Haven criteria are used for staging overt HE while neuropsychiatric and neurophysiological tests (psychometric hepatic encephalopathy score) are used for diagnosis of MHE. However objective methods for evaluation of the entire spectrum of no, minimal and overt HE are lacking [12]. Also, as yet there is no gold standard for grading or monitoring the progression of HE.
http://dx.doi.org/10.1016/j.dld.2015.04.014 1590-8658/© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jindal A, et al. Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.04.014
G Model YDLD-2881; No. of Pages 6
ARTICLE IN PRESS A. Jindal et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
2
The Bispectral index (BIS) is a recent technology used to measure the effects of anaesthetics and sedatives on the brain and consciousness. It uses a complex mathematical algorithm based upon descriptive EEG parameters from the frontal cortex to suggest various levels of sedation. BIS is the weighted sum of three sub parameters: “Beta Ratio”, a frequency domain feature; relative synchrony of fast and slow wave, “SynchFastSlow”, a bispectral domain feature; and “Burst suppression ratio”, a time domain feature. The BIS analysis uses a proprietary algorithm that allows different descriptors to dominate sequentially as the EEG changes its character [13]. A sensor placed on the patient’s forehead sends raw EEG waveforms to the monitor, where they are analyzed and the BIS index is calculated which ranges from 0 (isoelectric EEG) to 100 (completely awake) [13,14]. A recent study by Dahaba et al. [15] has shown the utility of BIS in overt HE and concluded that it is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease. We aimed to evaluate the role of BIS to diagnose minimal and overt HE, to grade HE levels, and monitor the response of overt HE and minimal HE to treatment.
2. Patients and methods The study was conducted in the Department of Gastroenterology at G. B. Pant Hospital, New Delhi, India from February 2014 to September 2014. It was a prospective case control, observer blinded study evaluating the role of BIS in patients with overt and minimal HE (Clinical Trial Registration number, CTRI/2014/03/004493). Consecutive cirrhotic patients attending the outpatient department or admitted to the Gastroenterology ward of GB Pant Hospital were eligible for the study. Written informed consent was obtained from each patient (and/or guardian); the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki was approved by the institutional review committee. Patients with liver cirrhosis (aged 18–70 years) were prospectively enrolled. Exclusion criteria were: use of sedatives, hypnotics or psychotropic drugs; concomitant neurological disorders affecting the mental state such as stroke, stupor, or dementia; lactulose therapy during the previous 6 weeks and history of recent alcohol intake (in the past 6 months). Diagnosis of cirrhosis was based on clinical, biochemical, ultrasonographic and liver histological findings if available. All cirrhotic patients without overt HE were screened for MHE. Diagnosis and grading of overt HE was done according to West Haven criteria. MHE was diagnosed according to Psychometric hepatic encephalopathy score (PHES score). PHES evaluation included digit symbol test (DST), number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT) and line-tracing test (LTT). A test was considered abnormal when the score was beyond ±2 SD from the score in the age and education-matched control group. MHE was diagnosed when the sum of all scores ≤−5 points [16]. Patients were evaluated for the aetiology and severity of liver disease (Child Turcotte Pugh [CTP] and Model for End-stage Liver Disease [MELD] score). The level of consciousness was assessed in patients with overt HE using Glasgow coma scale (GCS). Patients in the overt HE group (n = 120) received lactulose (30 ml two to three times daily orally or via nasogastric tube in cases of unconscious patients, to obtain 2–3 soft stools/day) for 7 days and their grades of HE were reassessed and recorded after 7 days. Patients in the MHE group (n = 60) received lactulose (30 ml two to three times daily orally to obtain 2–3 soft stools/day) for three months. All investigations and PHES scoring were repeated after
3 months of therapy. We also enrolled 20 patients with cirrhosis without HE, and 20 age and gender-matched healthy controls. All patients underwent complete blood count, liver function tests, serum electrolytes, serum creatinine, work up for aetiology of liver disease (including viral markers, history of alcohol intake, autoimmune liver disease, Wilson’s disease, lipid profile, blood sugar, body mass index, anti mitochondrial antibody, perinuclear anti-neutrophil cytoplasmic antibody) and arterial ammonia. 2.1. Bispectral index (BIS) recording We recorded BIS for all cirrhotic patients with overt HE/MHE along with cirrhotics without HE/MHE. Immediately before the BIS recording, the grade of overt HE was assessed clinically according to West Haven criteria and MHE by PHES score. Thereafter, a blinded anaesthesiologist recorded the BIS data in a quiet environment over an artefact-free period of 10 min, which took up to 15 min of total recording time. All noise, as well as verbal or tactile stimulation was avoided, thus preventing external stimuli from provoking a transient BIS response [17]. A BIS “Quatro” sensor strip was placed on the patient’s forehead according to the manufacturer’s instructions and connected to a BIS-XP monitor (version 3.4, Aspect Medical Systems, Newton, Massachusetts, USA). The BIS monitor was either connected to a laptop computer or to a printer for recording of BIS value. Conscious patients were instructed to remain calm with their eyes closed but not to fall asleep [18], and to try to keep their facial muscles completely relaxed [19]. Recordings were started after verifying a sustained low electromyography (EMG) activity and a signal quality index above 95%. Data from BIS index and EMG power, displayed in decibel (dB) units, were continuously collected and stored once every five seconds and at end of 10 min, mean BIS score was recorded. As BIS increases spuriously with high EMG activity [19], agitated patients with high EMG activity were excluded from the study and only recordings with low EMG activity and without technical artefacts (such as unexpected noise or unavoidable external stimulation) were accepted for analysis. Because BIS decreases with sleep [18], all conscious patients were interviewed at the end of the recordings, and patients who fell asleep during recording of BIS value were excluded from the study. We also recorded BIS score in 20 patients of liver cirrhosis without overt HE and MHE based on West Haven criteria and PHES respectively, and in 20 healthy controls at baseline. 2.2. Study follow up Patients with overt HE group were reassessed clinically after 7 days for the grade of HE, and at this time, the observer (anaesthesiologist) blinded to HE grade recorded the second BIS score. Patients with MHE were reassessed for the PHES score after 3 months. 2.3. Statistical analysis To date there is no data on BIS monitoring before and after lactulose therapy in patients of overt HE/MHE to allow prior sample size calculation. We enrolled 200 cirrhotic patients (30 each of overt HE grade I, II, III and IV, 60 of MHE and 20 without HE). Data were expressed as mean ± SD or median (range). The BIS cut off values for HE grade I was calculated as the mean of the lowest BIS value in HE grade I patients and the highest value in HE grade II patients, and in the same way was calculated for the other grades and patients of MHE and without encephalopathy. Comparison of BIS values in different grades of overt HE/MHE at baseline was done using two way analysis of variance (ANOVA) test followed by post hoc analysis (by Bonferroni method).
Please cite this article in press as: Jindal A, et al. Bispectral index monitoring for diagnosis and assessment of severity of hepatic encephalopathy in cirrhotic patients. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.04.014
G Model
ARTICLE IN PRESS
YDLD-2881; No. of Pages 6
A. Jindal et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
3
Table 1 Baseline demographic parameters, laboratory parameters and aetiology in the study groups. Parameter
Cirrhotics without HE (n = 20)
Cirrhotics with MHE (n = 60)
Cirrhotics with overt HE (n = 120)
p-Value
Mean age (years) Male gender (%) Mean CTP score Mean GCS Mean MELD score Mean arterial ammonia (mol/l) Aetiology Alcohol HBV HCV Cryptogenic Other
40.3 ± 12.1 12 (60%) 8.9 ± 1.8 15 13 ± 4 67.3 ± 24.9
42.6 ± 11.2 39 (65%) 9.2 ± 2.5 15 19 ± 5.4 70.3 ± 23.7
38.3 ± 10.3 90 (75%) 10.5 ± 1.87 11.5 ± 0.9 22.9 ± 4.6 90.5 ± 19.6
0.73 0.12 0.02 – 0.04 0.03
31 (52%) 11 (19%) 7 (11%) 9 (15%) 2 (4%)
60 (50%) 21 (17%) 13 (11%) 17 (14%) 9 (8%)
0.45
9 (45%) 4 (20%) 3 (15%) 3 (15%) 1 (5%)
HE: hepatic encephalopathy, MHE: minimal hepatic encephalopathy, CTP: Child Turcotte Pugh, GCS: Glasgow coma scale, MELD: model for end stage liver disease, HBV: hepatitis B virus, HCV: hepatitis C virus.
Receiver-operating characteristic (ROC) curves for BIS predictive value of West Haven grades were constructed, and the areas under the curves (AUC) were calculated and again BIS cut off was calculated. Correlation of mean BIS value/HE grades with arterial ammonia levels, CTP score and MELD score was assessed by using Spearman’s rank correlation analysis. Comparison of BIS values before & after treatment was performed using Student’s paired t test. ‘p’ value of
