Osmotic therapies added to antibiotics for acute bacterial meningitis

Meningitis is a condition where bacteria, fungi or viruses spread from the blood and infect the membranes and fluid that surround the brain and spinal cord. All types of meningitis are very serious but acute bacterial meningitis has a rapid onset and is usually fatal within hours to days without treatment. Signs and symptoms usually include high fever, severe headache, convulsions, coma and mental confusion. Even with antibiotics the mortality rate is 10% to 15% in children with bacterial meningitis and 20% to 30% in adults in high-income countries, rising to 50% in adults in low-income countries. Increased swelling of the brain caused by the infection is thought to contribute to death and may lead to complications in survivors such as long-term brain damage, deafness, epilepsy and learning difficulties in children. Bacterial meningitis is relatively rare in well-resourced settings but is more common in low-income countries, particularly where the prevalence of HIV is high.

Osmotic therapies function by increasing the concentration of the blood and exerting an osmotic pressure across a semi-permeable membrane (such as a cell wall or blood vessel lining in the brain) drawing water from the brain into the blood, thereby reducing pressure in the brain. This is theoretically advantageous if brain swelling is causing a reduction in brain function. Osmotic therapies can reduce brain swelling and potentially increase the rate of survival, or they could do harm. Glycerol is an osmotic treatment that was tested in the four trials included in this review, with a total of 1091 participants. No other osmotic treatments have been tested in randomised trials to date. This review detected no benefit from glycerol relating to death or neurological disabilities and one study in adults in Malawi suggested it may do harm. Deafness was slightly less common in the osmotic group at follow-up but the effect was small. No effect on epileptic seizures at follow-up was noted. Glycerol was not associated with any severe adverse effects. The number of trials included was small and only two of the included studies tested a large number of participants. All trials were from differently resourced healthcare settings and examined either adults or children.

Authors' conclusions: 

The only osmotic diuretic to have undergone randomised evaluation is glycerol. Data from trials to date have not demonstrated benefit on death, but it may reduce deafness. Osmotic diuretics, including glycerol, should not be given to adults and children with bacterial meningitis unless as part of carefully conducted randomised controlled trial.

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Background: 

Every day children and adults throughout the world die from acute community-acquired bacterial meningitis, particularly in low-income countries. Survivors are at risk of deafness, epilepsy and neurological disabilities. Osmotic therapies have been proposed as an adjunct to improve mortality and morbidity from bacterial meningitis. The theory is that they will attract extra-vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water from the brain into the blood. The intention is to thus reduce death and improve neurological outcomes.

Objectives: 

To evaluate the effects on mortality, deafness and neurological disability of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults.

Search strategy: 

We searched CENTRAL 2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November 2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and registers of ongoing clinical trials (April 2012). We also searched conference abstracts and contacted researchers in the field.

Selection criteria: 

Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.

Data collection and analysis: 

Two review authors independently screened the search results and selected trials for inclusion. We collected data from each study for mortality, deafness, seizures and neurological disabilities. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not.

Main results: 

Four trials were included comprising 1091 participants. All compared glycerol (a water-soluble sugar alcohol) with a control; in three trials this was a placebo, and in one a small amount of 50% dextrose. Three trials included comparators of dexamethasone alone or in combination with glycerol. As dexamethasone appeared to have no modifying effect, we aggregated results across arms where both treatment and control groups received corticosteroids and where both treatment and control groups did not.

Compared to placebo, glycerol may have little or no effect on death in people with bacterial meningitis (RR 1.09, 95% confidence interval (CI) 0.89 to 1.33, 1091 participants, four trials, low-quality evidence); or on death and neurological disability combined (RR 1.04, 95% CI 0.86 to 1.25).

Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30, 909 participants, three trials, low-quality evidence).

Glycerol may reduce the risk of subsequent deafness (RR 0.60, 95% CI 0.38 to 0.93, 741 participants, four trials, low-quality evidence).

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