QJM Advance Access originally published online on December 17, 2006
QJM 2007 100(1):37-40; doi:10.1093/qjmed/hcl131
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Hyponatraemia in adults with community-acquired bacterial meningitis
From the Departments of 1Neurology, 2Medical Microbiology and 3The Netherlands Reference Laboratory for Bacterial Meningitis, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Address correspondence to Dr M. Brouwer, Department of Neurology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands. email: m.c.brouwer{at}amc.uva.nl
Received 25 July 2006 and in revised form 24 August 2006
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Summary |
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Background: Hyponatraemia in adults with bacterial meningitis has been described as a common complication, but its true prevalence and clinical importance are unknown.
Aim: To investigate the prevalence, clinical characteristics and consequences of hyponatraemia in bacterial meningitis in adults.
Design: Nationwide observational cohort study.
Methods: We prospectively assessed the prevalence and clinical characteristics of hyponatraemia among 696 adults with community-acquired bacterial meningitis. Symptoms and signs on admission, blood and CSF test results, radiological examinations and complications during admission were recorded.
Results: Sodium levels were determined at admission in 685/696 episodes of bacterial meningitis (98%). Hyponatraemia (<135 mmol/l) was seen in 208/685 (30%) and was classified as severe (<130 mmol/l) in 38 (6%). Hyponatraemia developed during admission in an additional 53 episodes. Hyponatraemia was not associated with an increase in symptoms, with complications or with unfavourable outcome. Treatment for hyponatraemia was initiated in 16% of episodes, but did not influence its duration.
Discussion: Hyponatraemia appears both common and benign in adults with bacterial meningitis. In cases of severe hyponatraemia, we suggest the use of fluid maintenance therapy.
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Introduction |
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Bacterial meningitis is a serious, life-threatening disease.1 Its estimated incidence is 4–6 per 100 000 adults per year in developed countries, and Streptococcus pneumoniae and Neisseria meningitidis are the leading infective agents.2 The prevalence of hyponatraemia in adults with bacterial meningitis is unknown, although it has been described as a common complication.1 We describe the prevalence of hyponatraemia, and the clinical characteristics and outcome of patients with and without hyponatraemia, in a prospective nation-wide cohort study on community-acquired bacterial meningitis in adults.2
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Methods |
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In the Dutch Meningitis Cohort Study, a nationwide observational cohort study in the Netherlands, 696 episodes of community acquired acute bacterial meningitis were assessed prospectively in 671 patients.2 Eligible patients were aged >16 years, had bacterial meningitis confirmed by culture of CSF, and were listed in the database of the Netherlands Reference Laboratory for Bacterial Meningitis from October 1998 to April 2002. This laboratory provided daily updates of the names of hospitals where patients with bacterial meningitis had been admitted 2–6 days previously. The treating physician was contacted, and informed consent obtained from all participating patients or their legally authorized representatives. The Dutch Meningitis Cohort Study was approved by our ethics committee. Information was obtained using a case record form; symptoms and signs on admission, blood and CSF tests results, radiological examination and complications during admission were recorded. Serum sodium level was determined on admission.
Hyponatraemia was defined as a serum sodium level <135 mmol/l (mild 130–135, severe <130). The first occurrence, duration and treatment of hyponatraemia were recorded. Fluid restriction therapy was defined as fluid intake <1 l/day if the body temperature was <37°C, <1.5 l/day for body temperature 37–38°C, 2 l/day for 38–39°C and <2.5 l/day if >39°C.
Patients underwent a neurological examination at discharge, and outcome was graded using the Glasgow outcome scale. A favourable outcome was defined as a score of 5, an unfavourable outcome as a score of 1–4.
The Mann-Whitney U test was used to identify differences between groups in continuous variables, and dichotomous variables were compared by the 
2 test. All statistical tests were two-tailed, and a p value of <0.05 was regarded as significant. Analyses used SPSS (v. 12.0.1).
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All causative organisms were identified by cerebrospinal fluid (CSF) culture, yielding S. pneumoniae in 352 episodes (51%), N. meningitidis in 257 (37%), Listeria monocytogenes in 30 (4%), and other bacteria in 54 (8%).
On admission, sodium levels were determined in 685/696 episodes (98%). Hyponatraemia was present on admission in 208/685 episodes (30%), and classified as severe in 38/685 (6%). Median serum sodium was 136 mmol/l (range 120–156). The prevalence of hyponatraemia varied with the infecting organisms, being seen in 115/346 episodes of pneumococcal meningitis (33%), 55/254 episodes of meningococcal meningitis (21%), 22/30 episodes of L. monocytogenes meningitis (73%; proportion compared with all other patients, Fisher's exact test, p < 0.001), and 15/52 episodes caused by other micro-organisms (29%). Of the 38 episodes with severe hyponatraemia, eight occurred in patients with L. monocytogenes meningitis (21%; p < 0.001).
The classic symptoms and signs of nausea, headache, seizures and impaired consciousness (Glasgow Coma Score <14) on admission were found in similar proportions in patients with severe hyponatraemia, mild hyponatraemia and normonatraemia (Table 1). There was a significant association between the presence of hyponatraemia and the duration of symptoms: patients who had had symptoms for >24 h were more likely to have hyponatraemia (35% vs. 25%, p = 0.01). Signs and symptoms of nausea, vomiting and impaired consciousness on admission were similar in episodes with severe hyponatraemia to those with mild hyponatraemia. Serum potassium and creatinine levels in patients with and without hyponatraemia were also similar. A lumbar puncture was performed in all patients. Patients with hyponatraemia had lower CSF protein level (p = 0.003) and a lower CSF white cell count (p = 0.005). CSF opening pressures were measured in 216/696 patients, but there was no association between high CSF pressure and hyponatraemia.
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Cranial computed tomography (CT) was done at admission in 496 episodes (71%), identifying cerebral oedema in 48 episodes (10%). The proportion of patients with cerebral oedema was similar between patients with and without hyponatraemia (p = 0.87).
During the clinical course, hyponatraemia was seen in 186/696 episodes (27%), and was classified as severe in 42/696 (6%). The proportion of patients with seizures, impairment of consciousness, hydrocephalus and stroke in patients with severe, mild or no hyponatraemia was similar.
Treatment for hyponatraemia was initiated in 42/261 episodes (16%; 208 episodes on admission, an additional 53 during admission), and consisted of fluid restriction in 9/42 (21%). Treatment was given for 16/55 episodes of severe hyponatraemia (29%) and 26/206 episodes (13%) of mild hyponatraemia. Duration of hyponatraemia was recorded in 169 patients, with a median of 2 days (range 1–30). Duration of hyponatraemia did not differ between patients who received any kind of treatment and those who were not treated, irrespective of the severity of hyponatraemia. In 133/169 recorded episodes (79%) hyponatraemia resolved within 3 days.
Outcome was recorded in all patients. The case fatality rate in patients with hyponatraemia on or during admission was 22%, with an unfavourable outcome in 38% of episodes. Neither mild nor severe hyponatraemia was associated with an unfavourable outcome, death or the development of neurological sequelae, either overall or in subgroups according to causative organism.
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Discussion |
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In our adult patients with bacterial meningitis, hyponatraemia was a frequent but benign complication. Hyponatraemia was mostly mild, and we found no association with either severity of disease or outcome, suggesting that it is not an important problem in the general population of adults with community-acquired bacterial meningitis.
We found an exceptionally high rate of hyponatraemia in adults with meningitis due to L. monocytogenes (73%). Comparable high rates of hyponatraemia have also been described in tuberculous and Group A streptococcal meningitis.3,4 Hyponatraemia was associated with a longer duration of symptoms, a lower CSF white cell count and a lower level of CSF protein. This might imply that hyponatraemia needs time to develop, and is therefore more often found in patients with a less severe degree of inflammation.
The majority of the episodes of hyponatraemia resolved within 3 days without specific treatment. Only 3% of patients with hyponatraemia received a regimen with fluid restriction, and neither this nor any other form of treatment appeared to influence the duration of hyponatraemia. The aetiological mechanism of hyponatraemia in bacterial meningitis is unclear.5 It may result from the syndrome of inappropriate anti-diuretic hormone secretion (SIADH), the cerebral salt wasting (CSW) syndrome, or aggressive fluid resuscitation.1,5 Differentiation between SIADH and CSW relies on evaluation of the volume status,6 the sensitivity and specificity of this measurement are both low.7 In addition, several other causes or predisposing factors for hyponatraemia might have been present, e.g. congestive heart disease or diuretic use.8 These factors were not recorded in this study, which is a considerable limitation, and prevents conclusions about causality.
There are no clinical data on fluid management for hyponatraemia in adults with bacterial meningitis. A recent Cochrane review on this topic in children with bacterial meningitis identified six clinical trials, but only three met the inclusion criteria.9 Two of these trials also showed no effect of fluid restriction on serum sodium levels after 24 and 72 h compared to those treated with fluid maintenance; the effect on duration of hyponatraemia was not stated. The meta-analysis showed some evidence to support the use of intravenous maintenance fluids in preference to restricted fluid intake in the first 48 h in settings with high mortality rates, and where patients present late. However, where children present early and mortality rates are lower, there is insufficient evidence to guide practice. The fluid management used in our patients was not recorded, unless it was specifically intended to be a treatment for hyponatraemia.
In conclusion, hyponatraemia is a common and benign complication in adults with bacterial meningitis. Moderate hyponatraemia in bacterial meningitis is usually self-limiting and should be managed conservatively with regular checks of serum sodium. In patients with severe hyponatraemia, we would use fluid maintenance therapy instead of fluid restriction, although clear evidence is lacking.5,9
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We are indebted to many physicians in the Netherlands for their cooperation. The Dutch Meningitis Cohort Study was supported in part by a research grant from Roche Pharmaceuticals. JdG received a research grant from Baxter BV. DvdB received a research grants from the Meningitis Research Foundation UK and the Meerwaldt Foundation; and is supported by personal grants from the Netherlands Organization for Health Research and Development (ZonMw); NWO-veni grant 2006 (916.76.023) and NWO-rubicon grant 2006 (019.2006.1.310 [EC] .001).
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References |
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1. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. (2006) Community-acquired bacterial meningitis in adults. N Engl J Med 354 44–53.
2. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. (2004) Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 351 1849–59.
3. van de Beek D, de Gans J, Spanjaard L, Sela S, Vermeulen M, Dankert J. (2002) Group a streptococcal meningitis in adults: report of 41 cases and a review of the literature. Clin Infect Dis 34 e32–6.[CrossRef][ISI][Medline]
4. Davis LE, Rastogi KR, Lambert LC, Skipper BJ. (1993) Tuberculous meningitis in the southwest United States: a community-based study. Neurology 43 1775–8.
5. Moller K, Larsen FS, Bie P, Skinhoj P. (2001) The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis—how strong is the evidence? Scand J Infect Dis 33 13–26.[CrossRef][ISI][Medline]
6. Harrigan MR. (1996) Cerebral salt wasting syndrome: a review. Neurosurg 38 152–60.[CrossRef][ISI][Medline]
7. Chung HM, Kluge R, Schrier RW, Anderson RJ. (1987) Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 83 905–8.[CrossRef][ISI][Medline]
8. Adrogué HJ and Madias NE. (2000) Hyponatremia. N Engl J Med 342 1581–9.
9. Oates-Whitehead RM, Maconochie I, Baumer H, Stewart ME. (2005) Fluid therapy for acute bacterial meningitis. Cochrane Database Syst Rev 3 CD004786.
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