Why is the effect of differing volumes of initial fluid administration on death and various neurological sequelae in people with acute bacterial meningitis important?
Bacterial meningitis is an infection of the fluid in the spinal cord and surrounding the brain. Antibiotics are prescribed as treatment. Supportive care includes other drugs and the regulation of fluid intake. There has been disagreement about whether fluids should be restricted or unrestricted as there are potential risks from giving too much fluid (brain swelling) as well as too little fluid (shock).
The evidence is current to March 2016. We did not find any trials in adult populations and included three trials involving 420 children. All trials were set in countries where death rates for meningitis are high. In one study no funding source was mentioned. The remaining two studies were funded jointly by pharmaceutical concerns with government agencies and a charitable agency.
No studies reported important healthcare outcomes such as duration of hospital stay, raised intracranial pressure, or status epilepticus. An adverse effect in children with restricted fluid intake was that they were less likely to have low levels of sodium in their blood and therefore they would experience greater reductions in body fluids. An adverse effect of unrestricted fluid administration was reported in one study as short-term swelling of the face and low blood sodium levels one to two days after fluids were started, although the largest study found no difference in blood sodium levels.
The review found limited evidence from these trials in support of not restricting fluids in settings with high mortality rates. There is no evidence to guide clinicians about fluid therapy in adult patients with acute bacterial meningitis. There is a need for more research on these aspects in the future.
Quality of the evidence
Analysis of available trials found low quality evidence that there is no significant difference between maintenance versus restrictive fluid regimens for the outcome of death and acute severe neurological complications. There was also some evidence favouring maintenance fluid therapy over restricted fluids for chronic severe neurological events at three months follow-up, but the quality was very low.
The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.
Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. This is the latest update of a review first published in 2005 and updated in 2008 and 2014.
To evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae.
For this 2016 update we searched the following databases up to March 2016: the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, CINAHL, Global Health, and Web of Science.
Randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion.
All four of the original review authors extracted data and assessed trials for quality in the first publication of this review (one author, ROW, has passed away since the original review; see Acknowledgements). The current authors combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed the overall quality of evidence using the GRADE approach.
We included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality.The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants).