Increase in Serum Osmolality Is Possible Mechanism for the Beneficial Effects of Glycerol in Childhood Bacterial Meningitis

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Abstract
Oral glycerol reduces severe neurologic sequelae in childhood bacterial meningitis, but the mechanism awaits elucidation. We conducted a prospective, randomized, double-blind study in which the effects of glycerol and intravenous dexamethasone were compared with placebo recipients in an intensive care setting in India. Thirty-six children at age 2 months to 12 years with meningitis were treated with ceftriaxone and were randomized to receive also either dexamethasone intravenously, or glycerol orally, or both agents, or neither. The illness was monitored with preset criteria. The primary outcome measures were the changes in plasma osmolality and in urine output. Nine children received glycerol, 8 dexamethasone, 11 both agents, and 8 only placebo. The leading agents identified were Streptococcus pneumoniae, Haemophilus influenzae type b, and Staphylococcus aureus. Only the glycerol recipients increased plasma osmolality by up to 3% from the mean baseline of 294 mOsm/kg in the glycerol and 295 mOsm/kg in the glycerol-dexamethasone group. This change occurred within 6 hours, the critical period of treatment, and lasted <24 hours. Blood pressure was not affected, nor did urine output increase. The dexamethasone-only and placebo-only recipients showed immediate decrease in serum osmolality. Because excretion of the cerebrospinal fluid is inversely associated with plasma osmolality, we suggest that the glycerol-induced osmolality increase reduce the volume of cerebrospinal fluid, enhanced water movement back to the plasma by osmosis, increased cerebral blood flow, and thus, improved brain oxygenation.