Role of Hypertonic Saline Versus Mannitol in the Management of Raised Intracranial Pressure in Patients With ALF

Study Overview
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Brief Summary
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Patients with ALF (Acute liver Failure) would undergo a detailed clinical evaluation. Information would be collected regarding the onset and duration of symptoms, etiology, and severity of disease, other baseline clinical features, demographic characteristics, routine biochemical and hematological investigations. Patients would also be screened for the assessment of raised intracranial hypertension by either clinical or neuroimaging or by ONSD (optic nerve sheath diameter) and TCD (Transcranial doppler ultrasonography). Patient found to be having risen ICP (Intra Cranial Pressure) would be randomized in the two groups of the study. The group A would receive intravenous mannitol 20 to 30 minutes every 4 hourly where as those in the group B would be given 3% hypertonic saline as continuous infusion at a rate of 25ml /hr and titrated q4 hrs per sliding scale to achieve a target serum sodium level of 144-155 mmol/L .Both the groups would receive other supportive measures such as head end elevation, oxygen supplementation, dextrose infusion to maintain normoglycemia standard medical treatment.

Official Title
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Role of Hypertonic Saline Versus Mannitol in the Management of Raised Intracranial Pressure in Patients With ALF: A Randomized Open -Label Study

Conditions
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Acute Liver Failure

Intervention / Treatment
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* Drug: Mannitol
* Drug: 3% hypertonic saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Acute Liver Failure with age >18 yrs Grade III or grade IV HE with raised ICP Patient's next-of-kin consenting for the study protocol. Exclusion Criteria: Patients with ocular trauma. K/c/o DCM, congestive heart failure, cerebral aneurysm, intracranial pathology Serum Na>160 and s creat>1.5 mg% with oligurea

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mannitol<br>Treatment with mannitol intravenous (IV) bolus over 20 to 30 minutes. The dose is 0.25 g/kg IV as a 20% solution repeated every 4th hourly.(8) Mannitol infusion to be stopped if s osmolarity >320mm | Drug: Mannitol<br> <br> |
| Active Comparator: 3% hypertonic saline<br>Treatment with 3% hypertonic saline as continuous infusion. Continuous 3% NaCl infusion to be started at a rate of 25ml /hr and titrated q4hrs per sliding scale to achieve a target serum sodium level of <160 mmol/L. | Drug: 3% hypertonic saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study response to therapy at 12 hr in HTS Vs mannitol group in reduction of ICP (Intra Cranial Pressure) | ICP (Intra Cranial Pressure) as assessed by ONSD (Optic Nerve Sheet Diameter) < 5mm PS<1.2 Pupils - RTL(reaction to light) {if initially NTR(no reaction to light)} BP<150/90(if initially high) Pulse >60( if < 60) | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of arterial NH3 to raised ICT (Intra cranial Tension). |  | 2 years | 
| Survival. |  | 28 days | 
| Length of ICU/hospital stay. |  | 2 years |