Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections*

Abstract

Objectives: Mannitol is a commonly used osmotherapy agent in raised intracranial pressure. However, the side effects of mannitol are significant. In traumatic brain injury (adult and pediatric), hypertonic saline (3%) shows varied results in comparison with 20% mannitol. We compared the effect of 3% hypertonic saline versus 20% mannitol (using common dosing strategies) on raised intracranial pressure in pediatric acute CNS infections. Design: Open-label randomized controlled trial. Setting: PICU of a quaternary care academic institute. Patients: Children 1–12 years old, with raised intracranial pressure and modified-Glasgow Coma Scale scores less than or equal to 8, were enrolled. Interventions: Patients were randomly assigned to 20%-mannitol (n = 28), 0.5 gram/kg/dose versus 3%-hypertonic saline (n = 29), 10 mL/kg loading followed by 0.5–1 mL/kg/hr infusion. An intraparenchymal catheter was used to monitor the intracranial pressure. The primary outcome was the proportion of patients achieved target average intracranial pressure less than 20 mm Hg during 72 hours. Secondary outcomes were interventions, morbidity, and mortality. Measurements and Main Results: The proportion of patients with target average intracranial pressure (< 20 mm Hg) was higher in hypertonic saline-group as compared to mannitol-group (79.3% vs 53.6%; adjusted hazard ratio 2.63; 95% CI: 1.23–5.61). Mean (± se) reduction of intracranial pressure (–14.3 ± 1.7 vs –5.4 ± 1.7 mm Hg; p ≤ 0.001) and elevation of cerebral perfusion pressure (15.4 ± 2.4 vs 6 ± 2.4 mm Hg; p = 0.007) from baseline were significant in hypertonic saline-group. Mean (± se) intracranial pressure over 72 hours was lower (14 ± 2 vs 22 ± 2 mm Hg; p = 0.009), and cerebral perfusion pressure was higher (65 ± 2.2 vs 58 ± 2.2; p = 0.032) in hypertonic saline-group. Hypertonic saline-group had higher modified-Glasgow Coma Scale score at 72 hours (median, interquartile range 10; 7–11 vs 7; 3–9; p = 0.003), lower mortality (20.7% vs 35.7%; p = 0.21), shorter duration of mechanical ventilation (5 vs 15 d; p = 0.002), and PICU stay (11 vs 19 d; p = 0.016) and less severe neurodisability at discharge (31% vs 61%; p = 0.049). Conclusions: In pediatric acute CNS infections, 3%-hypertonic saline was associated with a greater reduction of intracranial pressure as compared to 20% mannitol.

GC–MS analysis of chemical constituents and determination of the total antioxidant capacity of adult powder of Periplaneta americana

“…D-Mannitol, is an important essential medicine in the World Health Organization (WHO) list of important medicines. It has anti-oxidation, anti-aging and other efficacies (Koko et al 2020), and can be used clinically to reduce intracranial pressure (Qureshi et al 1999;Rameshkumar et al 2020).…”

Application of bench studies at the bedside to improve outcomes in the management of severe diabetic ketoacidosis in children—a narrative review

“…In children with raised ICP secondary to acute CNS infection, 3% hypertonic saline was found to be better than 20% mannitol in control of invasively monitored ICP (33). In these children, the major contributory factors for diffuse cerebral edema included inflammatory, vasogenic, or cytotoxic edema due to various stages of illness based on bacterial or viral etiology.…”

Clinical effects of hypertonic saline boluses in children with severe traumatic brain injury

“…A recent paper concludes HTS bolus therapy may be superior to mannitol for both lowering ICP and increasing cerebral perfusion pressure (CPP) in adults 5 . There is now evidence that this also stands true in children on continuous infusions 6 . However, based on the randomised control trials (RCTs) that exist for bolus therapy the only positive level 2 recommendation in the guidelines is the ‘consideration’ to use 3% HTS boluses for ICP control 7–9 …”

“…Some physicians opt for continuous infusion, reporting to improve 90‐day favourable outcomes by 9.4% 14 . The most recent paediatric RCT compared 10 mL/kg loading followed by continuous infusion of 3% HTS to a 20% mannitol bolus and found that the HTS was associated with a greater reduction in ICP and less severe neurodisability at discharge 6 . However, to date there have been only three small RCTs 3,15,16 investigating 3% HTS boluses in children which form the basis for the current guidelines 9 .…”

“…14 The most recent paediatric RCT compared 10 mL/kg loading followed by continuous infusion of 3% HTS to a 20% mannitol bolus and found that the HTS was associated with a greater reduction in ICP and less severe neurodisability at discharge. 6 However, to date there have been only three small RCTs 3,15,16 investigating 3% HTS boluses in children which form the basis for the current guidelines. 9 The most recent of these compared its effect to other osmolar therapies and found HTS gave a faster resolution of raised ICP and was the only treatment to increase the CPP.…”