Osmotic therapies added to antibiotics for acute bacterial meningitis

What is the aim of this review?

The aim of this Cochrane Review is to collect and analyse trials evaluating osmotic therapies given orally or intravenously to people with acute bacterial meningitis. Cochrane authors collected and analysed all relevant studies to answer this question; they found five relevant studies.

Key messages

Giving glycerol, an osmotic diuretic, probably has little or no effect on death (moderate-certainty evidence), but may reduce subsequent deafness (moderate-certainty evidence) or neurological disability (low-certainty evidence). The evidence is current to 17 February 2017.

What was studied in the review?

In meningitis, the cerebrospinal fluid that surrounds the brain and spinal cord is infected, usually as a result of spread from the blood. Any form of meningitis can result in death or severe disability, but acute bacterial meningitis is rapidly fatal without treatment. Even with antibiotics, 10% to 15% of children with bacterial meningitis die in high-income countries with much higher rates in low-income settings. The infection causes the brain to swell, and this is thought to contribute to death and to long-term brain damage in survivors. Osmotic therapies increase the concentration of the blood by exerting an osmotic pressure across a semi-permeable membrane (such as a cell wall or blood vessel lining in the brain). This draws water from the brain into the blood, thereby reducing pressure in the brain. Potentially osmotic therapies could increase the rate of survival, or they could do harm.

What are the main results of the review?

We included five trials that compared glycerol with placebo in a total of 1451 patients with bacterial meningitis. In the studies steroids were often given as well, but this did not appear to modify any of the effects seen with glycerol.

This review detected no benefit from glycerol relating to death. There appeared to be marginal protection against deafness and against neurological disability. 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 tested a large number of participants. All trials were from different healthcare settings and examined either adults or children.

Authors' conclusions: 

Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Read the full abstract...
Background: 

Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.

This is an update of a Cochrane Review first published in 2013.

Objectives: 

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

Search strategy: 

We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015).

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. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence.

Main results: 

We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.

Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).

Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).

Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).

Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence).

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