Hepatic encephalopathy is a reversible neuro psychiatric state that complicates liver disease. Hepatic encephalopathy due to chronic liver disease has become one of the most important chronic healthproblems (1). Prevalence of hepatic encephalopathy is typically higher if ascertainment is based on electrophysiological measurements. Chu NS, Yang SS 1988 indicated that SEP may be useful in detecting sub clinical HE and in monitoring its clinical course and further stated that chronic portal- systemic shunting in liver cirrhosis may result in a minimal impairment of cerebral function and sensory conduction in the CNS (2). Chu NS 1997 found that, "Evoked potentials are objective and quantitative methods capable of evaluating functions of both peripheral and central nervous systems (PNS and CNS) (3). Daniel B. Nora et al, in 2000 has quoted"

Visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) have been proposed as tools in the diagnosis of sub clinical hepatic encephalopathy (HE) (4, 5). SU Changchun in 2008 concluded that, BAEP could supply the objective basis for early diagnosis and treatment on SHE patients (6). Clinical observation of the neuro psychiatric condition (7-10), psychometric tests (11, 12), and EEG recording (12) have been used to differentiate the degrees of hepatic encephalopathy due to liver cirrhosis, but none of them seems objective or sensitive enough to quantify the degree of coma, nor to detect, as well, the preclinical stages of hepatic encephalopathy. Halliday stated evoked potentials can reflect not only pure nerve diseases but also demyelination processes (13) and neurotransmitterchanges (14) in cortical and sub cortical neurones. By storing the EEG trace for a pre selected period after the stimulus and by averaging these tracers it is possible to cancel the random components of EEG and to average the evoked response (12, 15, 16, 17, 18). Neuro physiological tests can be used during follow up to demonstrate change in a patient’s condition (19, 20, 21, 22).

The measurement of somatosensory, visual and auditory evoked potentials is standard technique for assessment of neurotoxicity including subclinical state as a result of exposure to various chemicals and toxins. These potentials reflect functional integrity of sensory tract in the brain and help in identifying the sites impaired due to neurotoxic factors. The aim of this study is to evaluate the involvement of central nervous system in chronic liver disease induced hepatic encephalopathy and to test for recognition of the preclinical stage of HE. The objective is to use Brainstem Evoked Response Audiometry as a tool to assess conduction in auditory pathway in decompensated chronic liver disease subjects and compare with the controls.

Sample size 60

Study Design : Cross-sectional study. The present study has been conducted in the Neurophysiologylaboratory of Research Wing, Department of Physiology, Stanley Medical College, Chennai - 1 from 2010 to 2011 using Neuro Perfect PlusMedicaid Polyrite. Ethical approval from the Institutional Ethical Committee, Stanley Medical College, Chennai - 1 was obtained for the study. Study group: 60 decompensated chronic liver disease subjects were selected from liver clinic and Department of Medical Gastroenterology, control group: 60 age and gender matched healthy subjects with normal liver functions from the Master Health Check Up of our hospital. The ultrasound of healthy subjects performed under MHC package was taken to assess the well being of their liver and portal venous system, no evidence of psychiatric or neurological disorders, and no alcohol intake within last 6 weeks. Inclusion Criteria: age group - 30 to 50 years, both genders diagnosed decompensated liver disease subjects irrespective of aetiology. Child Pugh Criteria- A, B. Exclusion Criteria: Child Pugh Criteria C, smokers, alcohol intake within last 6 weeks, subjects with any hearing impairment of clinical causes and drug induced, systemic diseases like diabetes mellitus, hypertension, drugs acting on central nervous system, chronic associated disorders as cardiac decompensation, renal disease, subjects with cochlear implant/cardiac pacemaker, history of head injury or cerebrovascular accidents. The participants were made to relax and be comfortable prior to the test. The written and informed consent was obtained before subjects entered the study. The complete examination of external ear was done for both ears, wax was removed and audiometry was done. The laboratory temperature was maintained uniformly using air conditioner. The basic parameters of subjects like height, weight, pulse including body temperature were recorded.

Brainstem auditory evoked potentials were first recorded in 60 normal subjects. In order to establish reliability of the method, several repetitions of brainstem auditory evoked potential recording were performed. 60 age and gender matched chronic liver disease subjects of mixed aetiology were studied. 30 DCLD subjects were categorised as grade I hepatic encephalopathy and 30 DCLD without HE. The gold plated disc copper disc electrodes filled with conducting paste were placed on scalp because they are painless, have better stability and less chances of infection. The electrodes recorded from ipsilateral and contralateral mastoid processes were referred to as Oz and Cz respectively and ground, as Fz. Vertex is the suitable location since waves II–V has good amplitude with little muscle artefact. Montage Chosen: Active electrode- Ipsilateral mastoid: Oz. Reference electrode- vertex: Cz. Ground electrode-contra lateral mastoid: Fz. The electrode impedance was kept below 5 kΩ. The low filter is set at 100 Hz and high filter at 3000 Hz. The pulse moves the earphone diaphragm away from the subject’s ear, which is a rarefaction phase stimulus. Wave I amplitude is greater with rarefaction compared to condensation stimulus. Since recognition of wave I is very important, rarefaction click polarity was chosen. A 10 ms epoch after the click stimulus is averaged, amplified and displayed on the computer monitor. The click acoustic stimuli at a rate of 11 pulse per second at an intensity of 90 dB hearing level to the ear stimulated and masking sound (white noise) of 40 dB in non stimulated ear was given through head phone supplied by Medicaid (23, 24, 25). All the techniques of measurement, duration, instruments including research laboratory temperature were maintained uniformly throughout the study Parameters studied: The wave latency I, II, III, IV and V, inter peak latency I-III, I-V, III-V and amplitudes of waves were measured.

In this study, BAEP was recorded in 60 decompensated chronic liver disease (DCLD) subjects diagnosed by Medical Gastroenterology unit, who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. Brainstem auditory evoked potential of both the ears was tested. Absolute and interpeak wave latencies were measured. DCLD subjects were divided into two inter groups based on
presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade-I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Results were analysed by student independent t- test using SPSS software 11 versions. Statistical significance was tested using P value. The baseline characteristics of this study and control group showed the mean age of study groupis 45.18±3.76 and controls are 44.17±4.76. The mean
BMI of study group is 27.55±1.22 and controls are 27.15±1.96. The gender ratio of study group to control is 1:1. There is statistically significant prolongation of absolute latencies of waves III and V and interpeak latencies I-III, I-V and III-V between DCLD and control groups. There was also significant prolongation of absolute latencies of waves III and V and interpeak latencies I-III, I-V and III-V between HE and NHE.

In a report from the Japanese Committee on the safety of contrast media published in 1990, the overall incidence of reactions from ionic contrast was found to be 12.66% and to non ionic contrast was found to be 3.13% (8). In a study done in Boston in 2005, the incidence of reactions to non ionic contrast in patients undergoing CT was 0.7% (3). The incidence of adverse drug reactions in our study was 0.34%. Among patients who received non ionic contrast, the incidence was 0.78% (1 in 100 patients) and among patients who received ionic contrast, the incidence
was 0.26% (1 in 350 patients). The overall incidence of reactions reported in our study is less than that reported in other studies. It could be because the method that was followed in our study to collect data was spontaneous reporting in which underreporting is a known drawback.

Previous studies have shown that minor symptoms such as nausea, vomiting or sneezing are less common with non-ionic contrast (9-12) (Table III). In a study done in 1988, the incidence of sneezing was 0% with iohexol and 2.2% with metrizoate. The incidence of nausea was 0.8% with iohexol, 15.8% with metrizoate. The incidence of vomiting was 1.2% with iohexol and 9.7% with metrizoate (10). Among the ADRs reported to us, the proportion of mild reactions compared to moderate or severe reactions were significantly higher in patients who received ionic contrast (n=42) than those who received nonionic contrast (n=21) (p<0.05).

Renal failure had been reported in one patient with pre-existing diabetes and coronary artery disease who received ionic contrast. Studies have shown that the risk of nephropathy in patients with no pre existing risk factors is the same with ionic and non ionic contrast (13). However in patients with dehydration, pre-existing renal failure or diabetes the risk may be higher and non ionic contrast may be preferred in such patients (14).

In another study, the risk of contrast induced kidney injury was found to be the same in patients receiving iopromide (LOCM) and iodixanol (iso osmolar contrast media), even in patients with diabetes and when high volume of contrast is given (>500 ml), provided sufficient hydration is maintained (15). The main factor in pathophysiology of contrast induced nephropathy is due to reduction in renal perfusioncaused by direct effect of contrast media on the kidney (16). Hence maintaining sufficient hydration is necessary for patients at risk of contrast induced nephropathy.

The amount by which the use of non ionic contrast decreases the risk of nephropathy in patients with pre existing risk factors is yet to be determined. Drugs such as N - acetylcysteine, theophylline are being studied to see their effect in reducing the risk of contrast induced nephropathy (17). There is insufficient evidence to support the use of prophylactic administration of N-acetylcysteine in patients having a high risk of contrast induced nephropathy.

There have been reports of coronary vasospasm following contrast media administration (18-20). This might be the pathophysiology behind the symptoms of tightness of chest in one patient who received ionic contrast.

Anaphylactoid reactions can occur with both ionic and non ionic contrast. The risk of fatal reactions is the same with ionic and non ionic contrast media (21). In our study two patients developed cardiopulmonary arrest, one patient developed bronchospasm and one patient developed tightness of chest. Clinical opinion is divided regarding the use of premedication to prevent severe reactions to contrast media in high risk patients (22, 23).

Skin tests may be able to detect this hypersensitivity. Studies are being done to explore the use of skin tests for the selection of theappropriate contrast medium for the patient. The sensitivity and specificity are yet to be determined (24).

In our study, most reactions (n=53) occurred during or immediately after giving contrast. Ten reactions occurred within 30 minutes of giving contrast. Seven patients developed skin reactions and vomiting 15 minutes after giving contrast. They were all given non ionic contrast and had pre existing coronary artery disease. The other three patients did not have any pre existing medical conditions and were all given ionic contrast. Of these, one patient developed skin reaction 10 minutes after giving contrast, another patient developed bronchospasm 20 minutes after giving contrast and another patient developed vomiting and tightness of chest 30 minutes after giving contrast.

As per the standards issued by the Royal College of Radiologists, patients must remain in the department for at least 15 minutes after the contrast injection. In patients at increased risk of reaction this should be increased to 30 minutes (25).

Conclusion

The present study shows that nausea, vomiting and rashes are the most commonly observed ADRs associated with contrast media. Majority reactions observed were mild to moderate in severity. Most of the reactions occur immediately after the administration of contrast. More number of ADRs of mild nature was observed in patients receiving ionic contrast media.