Supplementary Material for: Mannitol is comparable to hypertonic saline for raised intracranial pressure in Acute Liver Failure (MAHAL Study): A RCT

Background: Raised intracranial pressure due to cerebral edema (CE) is central to development of hepatic encephalopathy in ALF. Mannitol (MT) & Hypertonic saline (HS) has been shown to improve CE. We compared the efficacy & safety of the two modalities Methods: ALF with CE were prospectively randomized in an open study to receive either 5 ml/kg of either 3% HS, as continuous infusion; titrated every 6 hourly to achieve serum sodium of <160(Group A; n=26) or 1 g/kg of 20% MN as a IV bolus, repeated every six hourly (Group B; n=25) in addition to standard ALF care. Primary end-point was reduction of intracranial pressure defined as optic nerve sheath diameter <5mm and middle cerebral arterial pulsatility index (PI) <1.2 at 12 hours. Results: Fifty-one patients with ALF, hepatitis E being commonest (33.3%), median jaundice to HE interval of 8(1-16) days, were randomized to HS (n=26) or MN (n=25). Baseline characteristics were comparable including King’s college criteria [>2: 38.4% vs.40%]. Overall, 61.5% patients in HS and 56% in MN group showed reduction in ICP at 12 hr. (p=0.25). Rebound increase in ICP indices was noted in 5(20%) patients in MT and none in HS (p<0.05) group. New onset acute kidney injury was commoner in MT than HS group. The ICU stay, and 28-day transplant free survival were not different between the groups. Conclusions: While both agents had comparable efficacy in reducing ICP and mortality in ALF patients was comparable, HS was significantly better in preventing reducing rebound CE with lower renal dysfunction.