Hyponatraemia, defined as a serum sodium concentration !135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

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Clinical practice guideline on diagnosis and treatment of hyponatraemia

The only natural reservoir of Neisseria meningitidis is the human nasopharyngeal mucosa. Depending on age, climate, country, socioeconomic status, and other factors, approximately 10% of the human population harbors meningococci in the nose. However, invasive disease is relatively rare, as it occurs only when the following conditions are fulfilled: (i) contact with a virulent strain, (ii) colonization by that strain, (iii) penetration of the bacterium through the mucosa, and (iv) survival and eventually outgrowth of the meningococcus in the bloodstream. When the meningococcus has reached the bloodstream and specific antibodies are absent, as is the case for young children or after introduction of a new strain in a population, the ultimate outgrowth depends on the efficacy of the innate immune response. Massive outgrowth leads within 12 h to fulminant meningococcal sepsis (FMS), characterized by high intravascular concentrations of endotoxin that set free high concentrations of proinflammatory mediators. These mediators belonging to the complement system, the contact system, the fibrinolytic system, and the cytokine system induce shock and diffuse intravascular coagulation. FMS can be fatal within 24 h, often before signs of meningitis have developed. In spite of the increasing possibilities for treatment in intensive care units, the mortality rate of FMS is still 30%. When the outgrowth of meningococci in the bloodstream is impeded, seeding of bacteria in the subarachnoidal compartment may lead to overt meningitis within 24 to 36 h. With appropriate antibiotics and good clinical surveillance, the mortality rate of this form of invasive disease is 1 to 2%. The overall mortality rate of meningococcal disease can only be reduced when patients without meningitis, i.e., those who may develop FMS, are recognized early. This means that the fundamental nature of the disease as a meningococcus septicemia deserves more attention.

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

http://media.hsl.washington.edu/media/classes/Nurs415Article8.pdf

Bacterial meningitis in children

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Recommendation for caution with irinotecan, fluorouracil, and leucovorin for colorectal cancer.

Despite favorable meta-analyses no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually. We conducted a prospective randomized double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously glycerol orally both agents or neither agent. Primary end points were death severe neurological sequelae or deafness with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models. H. influenzae type b pneumococci and meningococci were the main agents found among 654 patients; dexamethasone was given to 166dexamethasone and glycerol were given to 159 glycerol was given to 166 and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast glycerol and dexamethasone plus glycerol reduced severe neurological sequelae compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI] 0.13-0.76; P = .010) and 0.39 (95% CI 0.17-0.93; P = .033) respectively. For neurological sequelae and death the odds ratios were 0.44 (95% CI 0.25-0.76; P = .003) and 0.55 (95% CI 0.32-0.93; P = .027) respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio 0.27; 95% CI 0.09-0.77; P = .014). Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety availability low cost and oral administration also add to its usefulness especially in resource-limited settings. (authors)

Adjuvant Glycerol and/or Dexamethasone to Improve the Outcomes of Childhood Bacterial Meningitis: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

The objective of this prospective study was to examine the effect of fluid restriction on body water and the outcome of children with acute meningitis. Fifty consecutively hospitalized children with acute meningitis, divided into two groups (A, without hyponatremia ; and B, with hyponatremia), were randomly assigned to receive either normal maintenance (M) or restricted (R subgroup) (65 to 70% of M subgroup) fluids during the first 48 hours. Total body water, extracellular water (ECW), serum and urinary sodium and plasma and urinary osmolality were measured at admission and after 48 hours. In both groups children receiving restricted fluids showed a significant decrease in the mean total body water and ECW whereas body water remained unchanged in those on maintenance fluids. Children having an ECW reduction of 10 ml/kg or more in 48 hours had a significantly lower intact survival (10 of 28, 36%) than those with <10 ml/kg or no reduction of ECW (15 of 22, 64%) (P < 0.05). The mortality was also higher in the former (7 of 28, 25%) than in the latter (2 of 22, 9%). On multiple stepwise regression analysis, ECW volume at admission (partial r 2 0.20), ECW loss in 48 hours (partial r 2 0.13) and plasma osmolality at admission (partial r 2 0.22) were significantly related to outcome. We conclude that fluid restriction does not improve the outcome of acute meningitis. Indeed a decrease in ECW volume at 48 hours increases the likelihood of adverse outcome.

H. P. Narakesri

Papers

Fluid restriction does not improve the outcome of acute meningitis